Infección por SARS-COV-2/COVID-19.

Protocolo elaborado por Dr. Abraham Katime Zúñiga.

katime@dr.com

www.infectoface.com

Versión: 16-04-2021 (En revisión).

Recomendaciones de acuerdo con presentación clinica COVID-19.

Severidad Descripción
Enfermedad Pacientes sintomáticos sin
leve evidencia de neumonía viral o
hipoxia.
Grupos de riesgo para evolución
complicada por COVID-19:
-Edad > 60 años.
-Enfermedad cardiopulmonar.
-Hipertensión arterial cronica.
-Diabetes mellitus.
-Obesidad - IMC ≥ 30 kg/m2
-Enfermedad renal cronica.
-Inmunosupresión (trasplante,
cáncer avanzado, terapia
biológica, uso prolongado de
esteroides, etc).
-Infección VIH no controlada.
Recomendaciones
Sin factores de riesgo para gravedad:
X Salida.
X Recomendaciones generales.
X Signos de alarma.
X Tratamiento sintomático.
X Aislamiento obligatorio.
X Seguimiento cada 48-72 h por teleconsulta.
Con factores de riesgo para gravedad:
-Ausencia de biomarcadores de mal pronostico:
X Salida.
X Recomendaciones generales.
X Signos de alarma.
X Tratamiento sintomático.
X Aislamiento obligatorio.
X Seguimiento cada 24-48 h por teleconsulta.
-Presencia de biomarcadores de mal pronostico:
X Hospitalizar en sala general.
X Seguimiento intrahospitalario por 48-72 h.

No se requieren Biomarcadores
en pacientes sin factores de
riesgo.

Biomarcadores a realizar en
caso de pacientes con factores
de riesgo:
X Linfocitos (Hemograma).
X LDH.
X PCR.

Tratamiento sintomático por

dolor o fiebre con:
Dolex ActivGel capsulas 500 mg
(Acetaminofen), frasco por 24 y
 cajas por 10 y 20 cápsulas
líquidas. Dosis: 1-2 cápsulas
cada 4-6 horas, según sea
requerido. La dosis máxima
diaria es de 8 cápsulas (4000
mg) distribuidas en un periodo
de 24 horas. Verificar
precauciones y
contraindicaciones.
o
Espidifen tabletas 400 mg
(Ibuprofeno arginina), caja por
12 tabletas. Dosis: 1 tableta
cada 6 a 8 horas, dependiendo
de la intensidad del cuadro y de
la respuesta al tratamiento.
Verificar precauciones y
contraindicaciones.

Antigripales por síntomas:

Clarigrip, Tableta con 2 mg de
Maleato de Clorfeniramina, 5
mg de Clorhidrato de Fenilefrina
y 500 mg de Acetaminofén, caja
por 12 y 24 tabletas. Dosis: 1 a 2
tabletas cada 6 a 8 horas.
Verificar precauciones y
contraindicaciones.

Fernández-Niño JA, et al. Multimorbidity patterns among COVID-19

Enfermedad Adulto con signos clínicos de
Moderada neumonía (fiebre, tos, disnea,
taquipnea) sin signos de
Neumonía neumonía grave, con SpO2≥93%
en aire ambiente.
deaths: proposal for the construction of etiological models. Rev Panam
Salud Publica 44, 2020. https://doi.org/10.26633/RPSP.2020.166
X Definir manejo intrahospitalario en sala general según la
presencia de factores de riesgo y predictores de
severidad/mortalidad por COVID-19.
https://www.mdcalc.com/national-early-warning-score-news-
2#evidence

Biomarcadores a realizar:
X Linfocitos (Hemograma). X En caso de egresar indicar seguimiento cada 24 h por
X LDH. teleconsulta.
X PCR.

Enfermedad Adulto con signos clínicos de X Manejo intrahospitalario en Unidad de Cuidados

Grave neumonía (fiebre, tos, disnea, Intensivos o Intermedios.
 taquipnea) más uno de los
Neumonía siguientes:
grave -Frecuencia respiratoria >30
respiraciones/min.
-Dificultad respiratoria severa.
-SpO2<93% en aire ambiente.

Biomarcadores a realizar:
X Linfocitos (Hemograma).
X LDH.
X PCR.
X DIMERO D.
X FERRITINA.
X TROPONINA.

Enfermedad Síndrome de Dificultad X Manejo intrahospitalario en Unidad de Cuidados

critica Respiratoria Aguda – SDRA. Intensivos.
Sepsis.
Choque séptico.

Biomarcadores a realizar:
X Linfocitos (Hemograma).
X LDH.
X PCR.
X DIMERO D.
X FERRITINA.
X TROPONINA.

Asintomático Diagnostico por búsqueda activa X No requiere tratamiento.

de casos o contactos estrechos
no protegidos.
X No se requieren biomarcadores pronostico.
X Se debe indicar aislamiento por 10 días desde la toma
de la muestra para rt-PCR.
X No es necesario realizar control de detección de
anticuerpos o prueba de rt-PCR, como un requisito para
reincorporarse al trabajo.

Recomendaciones en caso de hospitalizar en sala general o unidad

de cuidados intermedios pacientes con sospecha o diagnostico
COVID-19.
INDICACIONES GENERALES.
 1. Hospitalizar por Medicina Interna.
2. Definir nivel de severidad del paciente.
3. Establecer National Early Warning Score (NEWS-2) como predictor de severidad y mortalidad
por COVID-19.
Modified NEWS score for use in COVID-19 (Liao et al).
NEWS-2 modificada debe realizarse en todos los pacientes para determinar su riesgo de
mortalidad y enfermedad grave.

*Edad (≥65 vs <65 años), mortalidad OR 6.17, (IC 95% 3.26-11.67), p<.001

Wu CH, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in
Wuhan, ChinaJAMA Intern Med. doi:10.1001/jamainternmed.2020.0994. Published online March 13, 2020.

La escala NEWS fue construida y validada en pacientes con infección por el virus de la influenza A/H7N9 y se recomienda como una
herramienta objetiva para decidir nivel de atención. En 2007 un reporte del Acute Medicine Task Force of The Royal College,
London, UK, recomendó la utilización de la escala NEWS en los servicios de urgencias. Un estudio que evaluó una base de datos con
198.755 signos vitales obtenidos de 35.585 pacientes, demostró que esta escala tiene una buena capacidad para discriminar
pacientes en riesgo para un desenlace combinado de paro cardiaco, ingreso no anticipado a UCI o muerte dentro de las primeras 24
horas de atención; de esta manera genera una gran oportunidad para el establecimiento temprano de una intervención clínica que
cambie el pronóstico del paciente. La escala NEWS-2 modificada incluye la variable edad (<65 o ≥65 años). El nivel de atención que
requiere el paciente con diagnóstico de infección por COVID-19, se establece a través de una escala de puntuación así:

- Score 0-1 punto: Manejo domiciliario, aislamiento obligatorio, tratamiento sintomático, recomendaciones generales, signos y
sintomas de alarma. Realizar Pulsioximetria cada 6 a 12 horas (si se encuentra disponible).
- Score 2-4 puntos: Manejo en salas de hospitalización, área COVID-19. Realizar Pulsioximetria cada 6 horas.
- Score 5-6 puntos: Manejo en UCI, área COVID-19.
- Score ≥ 7 puntos sin condición extremadamente grave o irreversible y con alta posibilidad de recuperación: Traslado a UCI, área
COVID-19.
- Score ≥ 7 puntos con condición extremadamente grave y con datos de irreversibilidad o enfermedad terminal: No ingresar a UCI y
trasladar a salas de hospitalización con acompañamiento familiar y consulta a experto en bioética y cuidados paliativos.
Como alternativa a la escala NEWS-2 modificada se podría utilizar el score de riesgo COVID-19-GRAM, descrito con datos de 1.590
pacientes en 575 hospitales de China. Esta fue una cohorte retrospectiva, multicéntrica, en la que se recogieron un total de 72
variables entre demográficas, médicas, clínicas (signos y síntomas), imagenológicas y de resultados de laboratorios. Utilizando la
metodología de regresión LASSO (Least Absolute Shrinkageand Selection Operator) construyen un modelo de regresión
multivariable resultando en un score de riesgo predictivo para desarrollar enfermedad critica en pacientes con COVID-19
confirmado al momento de la admisión. De las72 variables iniciales 10 fueron predictores independientes estadísticamente
significativos para el desarrollo de enfermedad crítica. Estas variables fueron: anormalidad radiologica (OR: 3,39; 95% IC: 2,14-5,38;
p < 0,001), edad (OR: 1,03; 95% IC: 1,01-1,05; p = 0,002), hemoptisis (OR: 4,53; 95% IC: 1,36-15,1; p = 0,01), disnea (OR: 1,88; 95%
IC: 1,18-3,01; p = 0,01), disminución del estado de conciencia (OR: 4,71; 95% IC: 1,39-15,9; p = 0,01), número de comorbilidades
(OR: 1,60; 95% IC: 1,27-2,0; p < 0,001), historia de cáncer (OR: 4,07; 95% IC: 1,23-13,4; p = 0,02), relación neutrófilos-linfocitos (OR:
1,06; 95% IC: 1,02-1,10; p = 0,003), LDH (OR: 1,002; 95% IC: 1,001-1,002; p < 0,001) y bilirrubina directa (OR: 1,15;95% IC: 1,06-1,24;
p = 0,001). El valor promedio de la AUC para predecir enfermedad crítica en esta cohorte de pacientes fue de 0,88 (95% IC: 0,85-
0,91); muy superior al compararlo con el score CURB-65 cuyo valor predictivo para la misma cohorte tuvo una AUC de 0,75 (95% IC:
0,70-0,80). Esta diferencia se dio con un valor de p < 0,01.

Calculadora COVID-19-GRAM: http://118.126.104.170/

Liao, X., Wang, B. & Kang, Y. Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the
experience in Sichuan Province, China. Intensive Care Med 46, 357–360 (2020). https://doi.org/10.1007/s00134-020-05954-2

https://www.mdcalc.com/national-early-warning-score-news-2#evidence

Myrstad M, et al. National Early Warning Score 2 (NEWS2) on admission predicts severe disease and in-hospital mortality from
Covid-19 – a prospective cohort study. Scand J Trauma Resusc Emerg Med. 2020; 28: 66. Published online 2020 Jul 13.
doi: 10.1186/s13049-020-00764-3

Accini JL, et al. Actualización de la Declaración de consenso en medicina critica para la atención multidisciplinaria del paciente con
sospecha o confirmación diagnóstica de COVID-19 [Updated Consensus statement on critical medicine for the multidisciplinary care
of the patient with a suspected or confirmed diagnosis of COVID-19]. Acta Colombiana de Cuidado Intensivo. 2020; 20: 1-112.
doi: 10.1016/j.acci.2020.09.004

4. Revisar reportes de paraclínicos que identifican pacientes de mal pronóstico:

- Linfopenia (menor de 800 células/µl)
Wang K, et al. 15-day mortality and associated risk factors for hospitalized patients with COVID-19 in Wuhan, China:
an ambispective observational cohort study. Intensive Care Med (2020) 46:1472–1474.
https://doi.org/10.1007/s00134-020-06047-w

El conteo de linfocitos superior a 1.064 células/µl fue un factor protector frente a la enfermedad grave
(OR 0,99; p=0,001). Otros resultados asociados con la mortalidad y la gravedad fueron la elevación de
las enzimas hepáticas por encima de 100 UI/L, el aumento de la LDH (>470 UI/L) y de la proteína C
reactiva.

Motta JC, et al. Factores pronósticos en pacientes hospitalizados con diagnóstico de infección por SARS-CoV2 en
Bogotá, Colombia. Biomédica. 2020;40(Supl.2):116-30. https://doi.org/10.7705/biomedica.5764

Relación Neutrófilos/Linfocitos:

According to the NLR and age stratifcation, the incidence of critical ill patients with NLR≥3.13 and aged ≥50 years
was 50%, and 9.1% in aged ≥50 years and NLR<3.13 patients.

Liu J, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the
early stage. J Transl Med 18, 206 (2020). https://doi.org/10.1186/s12967-020-02374-0
- Dímero D elevado (mayor a 1000 ng/ml o ug/L)
Mortalidad: OR 18.42; 95% IC 2.64–128.55
Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a
retrospective cohort study. Lancet 2020; 395(10229): 1054–1062.

The effect of various potential risk factors on patients with severe COVID-19 at admission.

Li X, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. Journal of Allergy and
Clinical Immunology, Volume 146, Issue 1, 2020, Pages 110-118. https://doi.org/10.1016/j.jaci.2020.04.006

Dynamical changes of the risk factors in the patients with COVID-19 during hospitalization
Huang Y, et al. (2020) A cohort study of 676 patients indicates D-dimer is a critical risk factor for the
mortality of COVID-19. PLoS ONE 15(11): e0242045. https://doi.org/10.1371/journal.pone.0242045

A total of 176 patients with confirmed COVID-19 diagnosis were included. On presentation, the unadjusted odds for
the need of IMV (OR 2.5, 95% CI 1.3–4.8, p = 0.012) and upgrade to ICU (OR 3.2, 95% CI 1.6–6.5, p = 0.002) were
significantly higher for patients with CRP (>101 mg/dl). Similarly, the unadjusted odds of in-hospital mortality were
significantly higher in patients with high CRP (>101 mg/dl) and high D-Dimer (>501 ng/ml), compared to
corresponding low CRP (<100 mg/dl) and low D-Dimer (<500 ng/ml) groups on day-7 (OR 3.5, 95% CI 1.2–10.5, p =
0.03 and OR 10.0, 95% CI 1.2–77.9, p = 0.02), respectively. Both high D-Dimer (>501 ng/ml) and high CRP (>101
mg/dl) were associated with increased need for upgrade to the ICU and higher requirement for IMV on day-7 of
hospitalization. A multivariate regression model mirrored the overall unadjusted trends except that adjusted odds
for IMV were high in the high CRP group on day 7 (aOR 2.5, 95% CI 1.05–6.0, p = 0.04).

Ullah W, et al. Predictability of CRP and D-Dimer levels for in-hospital outcomes and mortality
of COVID-19. Journal of Community Hospital Internal Medicine Perspectives, 10:5, 402-408.
DOI: 10.1080/20009666.2020.1798141
 Alternativa al Dimero D: Fibrinogeno mayor a 900 mg/dL.

- PCR elevada (mayor a 41.8 mg/L)

Mortalidad: Sensibilidad 88.89 % - Especificidad 72.73% - VPP 66.67 % - VPN 91.35 % - OR 4.394; 95%
IC 1.924–10.033; p < 0.001
Liu F, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin
Virol. 2020 Jun; 127: 104370.

Huang H, et al. Prognostic Factors for COVID-19 Pneumonia Progression to Severe Symptoms Based on Earlier
Clinical Features: A Retrospective Analysis. Front. Med. 7:557453. doi: 10.3389/fmed.2020.557453

A meta-analysis by Huang et al. described nearly three times increased risk of mortality amongst patients with
CRP ≥10mg/L.

Huang I, et al. Creactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: A meta-
analysis. Ther Adv Respir Dis 2020; 14:1753466620937175.

In a study by Luo et al. CRP >41.4mg/L was 90.5% sensitive and 77.6% specific for mortality amongst hospitalised
patients.

Luo X, et al. Prognostic value of C-reactive protein in patients with COVID-19. Clin Infect Dis 2020; ciaa641. doi:
10.1093/cid/ciaa641.

“Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L,
interquartile range (IQR) 53–169]. CRP concentrations above the median value were associated with VTE [8.3%
vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61–3.36], AKI (43.0% vs. 28.4%; aOR 2.11,
95% CI 1.76–2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37–3.37), and mortality (32.2% vs. 17.8%;
aOR 2.59, 95% CI 2.11–3.18), compared with CRP below the median. A dose response was observed between
CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were
consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the
greatest risk of adverse outcomes.”

Smilowitz NR, et al. C-reactive protein and clinical outcomes in patients with COVID-19, European Heart Journal,
 2021;, ehaa1103, https://doi.org/10.1093/eurheartj/ehaa1103

- LDH elevada (mayor a 353.5 UI/L)

LDH mayor a 359.5 UI/L; Mortalidad: Sensibilidad 93.8% - Especificidad 88.2% - OR: 40.50; 95% IC 3.35-
449.28; p= 0.003
Li C, et al. Elevated Lactate Dehydrogenase (LDH) level as an independent risk factor for the severity and mortality
of COVID-19. Aging (Albany NY). 2020; 12(15): 15670-15681. doi: 10.18632/aging.103770

LDH mayor a 353.5 UI/L; Mortalidad: Sensibilidad 94.9% - Especificidad 89.2% - OR: 5.985; 95% IC
1.498-23.905; p= 0.011
Dong X, et al. Prognostic value of lactate dehydrogenase for in-hospital mortality in severe and critically ill patients
with COVID-19. Int J Med Sci 2020; 17(14):2225-2231. doi: 10.7150/ijms.47604

LDH mayor a 445 UI/L; Mortalidad: OR: 2; 95% IC 1.21-3.30; p= 0.007

Li X, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. Journal of Allergy and
Clinical Immunology, Volume 146, Issue 1, 2020, Pages 110-118. https://doi.org/10.1016/j.jaci.2020.04.006

Tortonese S, et al. COVID-19 in Patients on Maintenance Dialysis in the Paris Region. Kidney Int Rep (2020) 5, 1535–
1544. https://doi.org/10.1016/j.ekir.2020.07.016

Bartziokas K, et al. Lactate dehydrogenase, COVID-19 and mortality. Med Clin (Barc). 2020.
https://doi.org/10.1016/j.medcli.2020.07.043

Henry BM, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality:
A pooled analysis. Am J Emerg Med. 2020 Sep;38(9):1722-1726. doi: 10.1016/j.ajem.2020.05.073

Acharya D, et al. Mortality Rate and Predictors of Mortality in Hospitalized COVID-19 Patients with Diabetes.
Healthcare 2020, 8, 338; doi: 10.3390/healthcare8030338

Muldani R, et al. COVID-19: Correlation Between CRP and LDH to Disease Severity and Mortality in Hospitalized
COVID-19 Patients. Med Hosp 2020; vol 7 (1A): 144–149. https: //doi.org/10.36408/mhjcm.v7i1A.467

Velavan TP, et al. Mild versus severe COVID-19: Laboratory markers. International Journal of Infectious Diseases 95
(2020) 304–307. https://doi.org/10.1016/j.ijid.2020.04.061

Hu J, et al. Combination of serum lactate dehydrogenase and sex is predictive of severe disease in patients with
COVID-19, Medicine: October 16, 2020 - Volume 99 - Issue 42 - p e22774.
doi: 10.1097/MD.0000000000022774

Malik P, et al. Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis. BMJ
Evidence-Based Medicine. Published Online First 15 September 2020. doi: 10.1136/bmjebm-2020-111536
 Yu T, et al. Association Between Clinical Manifestations and Prognosis in Patients with COVID-19. Clinical
Therapeutics/Volume 42, Number 6, 2020. https://doi.org/10.1016/j.clinthera.2020.04.009

Bonetti G, et al. Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of
Valcamonica, Italy. Clin Chem Lab Med 2020; 58(7): 1100–1105. https://doi.org/10.1515/cclm-2020-0459

Ferritina elevada (mayor a 723 ng/ml o ug/L)

Evaluation of different coordinates for these curves revealed that CRP ≥45.5 mg/l had sensitivity of 86.36% and
specificity of 88.89% for predicting mortality. Similarly, serum ferritin ≥723 ng/ml at admission had a sensitivity of
95.45% and specificity of 86.57% for predicting mortality; whereas, LDH ≥428.5 U/l had sensitivity of 90.91%
and specificity of 80.56% for predicting mortality.

Arshad AR, et al. Association of Inflammatory Markers with Mortality in COVID-19 Infection. J Coll Physicians Surg
Pak 2020; 30(Supp2): S158-S163.
https://jcpsp.pk/article-detail/association-of-inflammatory-markers-with-mortality-in-covid19-infection

Ayanian S, et al. The association between biomarkers and clinical outcomes in novel coronavirus pneumonia in a US
cohort. Biomark. Med. (2020) 14(12), 1091–1097. Published Online:17 Jul 2020. https://doi.org/10.2217/bmm-
2020-0309

Herold et al. Documented, serum ferritin an AUC of 0.750 to predict need for mechanical ventilation
using a cut-off of 1285 ng/ml.

Herold T, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy
Clin Immunol 2020; 146(1):128-36. e124. doi: 10.1016/j.jaci.2020.05.008.
5. Habitación individual o traslado a zona hospitalaria para pacientes con diagnostico o
sospecha de COVID-19.
6. Aislamiento de contacto – gotas.
Se recomienda seguir las precauciones estándar más precauciones por contacto (bata
antifluido y guantes) y por gotas (mascarilla quirúrgica y gafas o visores protectores), en
caso de tener contacto a menos de dos metros del paciente, cuando no se hagan
procedimientos generadores de aerosoles.
Respirador N95 o su equivalente, cuando se realicen procedimientos generadores
de aerosoles.
7. Dieta según características del paciente por nutricionista clínica.
8. Se recomienda permanecer el mayor tiempo posible en decúbito prono.
9. Suplencia de Oxigeno por cánula nasal convencional o de alto flujo o mascara facial con
bolsa de reservorio según sea el caso.

Se recomienda no suministrar de forma rutinaria oxígeno si la saturación de oxígeno es

≥ 93%, y no se evidencian signos clínicos de dificultad respiratoria durante la
monitorización continua del patrón respiratorio.

Se recomienda colocar mascarilla quirúrgica por encima de la cánula nasal en el

paciente con sospecha o diagnóstico de COVID-19 y mantener una distancia mínima de
2 metros con otros pacientes.

Se propone iniciar la oxigenoterapia por cánulas de bajo flujo y ajustar el flujo (máximo
5 L) hasta alcanzar la SaO2 objetivo ≥ 93%; si el paciente se encuentra en estado crítico
iniciar con mascarilla con bolsa de reservorio (a 10-15 L/min). Una vez que el paciente
esté estable, el objetivo de oxigenación es mantener niveles de SaO2 >90% en pacientes
no embarazadas y entre 92-95% en pacientes embarazadas.

Valores normales OXIMETRIA DE PULSO – Colombia:

Un estudio en Colombia evaluó la SaO2 en 264 hombres y mujeres sanas
entre 18 y 30 años en altitudes entre 970 m y 2600 m sobre el nivel del mar,
encontrando pocas diferencias, pero siendo menor a 2600 m (SaO2 promedio hombres
93,6 % vs 94,8% mujeres 93,6% vs 96,4%). Hay que tener en cuenta que en adultos
mayores la PaO2 y SaO2 tiende a disminuir con la edad. En Bogotá, la presión arterial de
oxigeno (PaO2) puede pasar de 68-70 mmHg en menores de 30 años a 62-60 mmHg en
hombres y mujeres mayores de 70 años, esto corresponde a una SaO2 calculada de 94%
y 92%, respectivamente.
En Medellín a 1538 m sobre el nivel del mar, un estudio de 76 adultos sanos entre 20 y
45 años encontró una PaO2 media 80 mmHg, (IC95%: 79,7-81,5) que corresponde a una
SaO2 calculada de 96%, similar a la hallada en el estudio anteriormente mencionado
(1520 m: 95,5%).
 A pesar de no tener evidencia suficiente para definir cuándo sospechar hipoxemia en las
diferentes alturas y en diferentes edades, sugerimos guiarnos por los datos que
tenemos y los conceptos fisiológicos mencionados y recomendamos que, a menos de
2200 m de altitud, sospechar hipoxemia cuando la SpO2 es menor de 92% y definir
desaturación y probable hipoxemia significativa cuando la SpO2 es menor de 88%. A
2600 m sugestivo de hipoxemia SpO2 menor de 90% e hipoxemia significativa y pensar
en usar oxigeno cuando la SpO2 es menor de 85-86%.

USO E INTERPRETACIÓN DE LA OXIMETRIA DE PULSO. Convenio 519 de 2015.

Bogotá D.C. agosto del 2016
https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENT/uso-
interprtn-oximetria-pulso.pdf

10. Tapón venoso o líquidos endovenosos Lactato de Ringer 30-60 cc/hora.

Se recomienda un manejo conservador de líquidos para evitar un balance positivo que
podría deteriorar la oxigenación.
11. Verificar historial de alergias a medicamentos del paciente.
12. Monitorizar Saturación arterial de Oxigeno con pulso oximetría cada 12 horas.
13. Control de signos vitales y avisar cambios.
14. Curva térmica.
15. Control de líquidos administrados y eliminados, evitar sobrecarga hídrica de los
pacientes.
16. Recomendaciones generales y signos de alarma.
17. En caso de deterioro clínico (respiratorio o hemodinámico) presentar caso en la UCI.
18. En caso de pacientes con hipertensión arterial crónica de base, indicar antihipertensivos
si tensión arterial es mayor de 130/80 mm Hg.
No se recomienda suspender o cambiar ARAII o IECA si es del caso.
19. Gestionar con epidemiologia hospitalaria elementos de protección personal (EPP) para
equipo sanitario a cargo de paciente en zona hospitalaria, según indicaciones del
protocolo establecido.
20. Notificar caso y contactos estrechos comunitarios a epidemiologia hospitalaria para
indicaciones de aislamiento preventivo y toma de muestras rt-PCR o prueba rápida para
detección de antígenos (PRDA).
A. Persona asintomática con o sin factores de riesgo que es contacto estrecho no
conviviente de un caso confirmado con COVID-19:
 • Dejar en aislamiento, insistir en medidas de prevención y notificación temprana en
caso de aparecer síntomas.
• Tomar rt-PCR o PRDA dentro de los 7 a 10 días del contacto estrecho.
- Si rt-PCR o PRDA es positiva y paciente persiste asintomático: continuar aislamiento
por 10 días desde la toma de la muestra, en caso de pacientes con inmunosupresión
de base se sugiere continuar aislamiento por 15 días desde la toma de la muestra.
- Si rt-PCR o PRDA es negativa y paciente se encuentra asintomático, puede reiniciar
sus actividades sociales y laborales con medidas de prevención (monitoreo diario de
síntomas, uso continuo de tapabocas, lavado frecuente de manos, y
distanciamiento social).
Recomendación CDC 02-12-2020:
Quarantine can end after Day 7 if a diagnostic specimen tests negative and if no symptoms were
reported during daily monitoring. The specimen may be collected and tested within 48 hours
before the time of planned quarantine discontinuation (e.g., in anticipation of testing delays), but
quarantine cannot be discontinued earlier than after Day 7.

 With this strategy, the residual post-quarantine transmission risk is estimated to be about
5% with an upper limit of about 12%.

- Si no se logra realizar la rt-PCR o PRDA y persiste asintomático, se recomienda

aislamiento domiciliario por 10 a 14 días desde el momento de la exposición.
Si a los 10 dias de aislamiento no se han presentado síntomas puede finalizar la
cuarentena, reiniciar actividades sociales y laborales con medidas de prevención
(monitoreo diario de síntomas, uso continuo de tapabocas, lavado frecuente de
manos, y distanciamiento social).
Recomendación CDC 02-12-2020:
Quarantine can end after Day 10 without testing and if no symptoms have been reported during
daily monitoring.

 With this strategy, residual post-quarantine transmission risk is estimated to be about 1%

with an upper limit of about 10%.

For instance, at Day 10 with symptom monitoring but without diagnostic testing, the estimated residual post-quarantine
transmission risk was 1.4% (range 0.1%-10.6%). However, with the addition of diagnostic testing of a specimen collected
up to 48 hours before Day 10, the estimated post-quarantine transmission risk was reduced to 0.3% (range 0.0%-2.4%) for
RT-PCR testing, and 1.1% (0.1%-9.5%) for antigen testing with a test that had a diagnostic sensitivity of 70%.
Modeled estimates of post-quarantine transmission risk quarantine duration. The light blue bars
indicate the daily post-quarantine transmission risk if there is no clinical evidence of COVID-19
elicited during daily symptom monitoring. The dark blue bars indicate the post-quarantine
transmission risk with the addition of a negative RT-PCR result from a specimen collected 24-48
hours prior.
https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-options-to-reduce-
quarantine.html

B. El núcleo familiar que es contacto estrecho debe permanecer en aislamiento

estricto por 10 a 14 días, a partir del último día de la exposición. No se realizará
toma de muestra a personas asintomáticas dentro del núcleo familiar, dado que se
consideran casos probables por nexo epidemiológico.
Si a los 10 dias de aislamiento no se han presentado síntomas puede finalizar la
 cuarentena, reiniciar sus actividades sociales y laborales con medidas de prevención
(monitoreo diario de síntomas, uso continuo de tapabocas, lavado frecuente de
manos, y distanciamiento social).

“A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated
household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI,
4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index
cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95%
CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other
family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) tan in households
with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%).”

Madewell ZJ, et al. Household Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Netw
Open. 2020;3(12): e2031756. doi:10.1001/jamanetworkopen.2020.31756

“27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the
transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days.
Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly
more likely to be
infected than children aged 2–5 years (odds ratio [OR] 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same
exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58,
1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases
were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts,
and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI
0·24–0·26] to 0·12 [0·10–0·13]) and by 63% among secondary cases (from 0·17 [0·16–0·18] to 0·063 [0·057–0·070]).
Using the transmission model on data available after Feb 1, we estimated that individuals with asymptomatic infections were about 80% less likely to
infect others than symptomatic cases.”

Fang Li, et al. Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a
retrospective observational study. Lancet Infect Dis 2021. Published Online January 18, 2021.
https://doi.org/10.1016/S1473-3099(20)30981-6

“The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of
individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these
baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all
transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from
presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of
these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with
infection but without symptoms.”

Johansson MA, Quandelacy TM, Kada S, et al. SARS-CoV-2 Transmission From People Without COVID-19 Symptoms.
JAMA Netw Open. 2021;4(1): e2035057. doi:10.1001/jamanetworkopen.2020.35057

Options to Reduce Quarantine for Contacts of Persons with SARS-CoV-2 Infection Using Symptom Monitoring and
Diagnostic Testing. Updated Dec. 2, 2020.
https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-options-to-reduce-quarantine.html

21. Según reportes de estudios microbiológicos realizar los ajustes que sean del caso en la
terapia antimicrobiana.
- Si reporte rt-PCR o PRDA en aspirado traqueal o hisopado nasofaríngeo para SARS
CoV-2 es negativo y cuadro clínico- imagenológico es compatible con COVID-19, enviar
nueva muestra de aspirado traqueal o secreciones traqueobronquiales con 24 a 72 h de
diferencia y solicitar anticuerpos IgG-IgM SARS-CoV-2 si paciente tiene más de 11 días
de evolución con respecto al inicio de los síntomas.
- Si se descarta coinfección por Influenza Virus, suspender Oseltamivir VO.
- Si se descarta coinfección bacteriana, suspender antimicrobianos IV – VO.
22. En caso de considerar egreso, notificar previamente a la secretaria de salud
departamental o distrital según sea el caso y EPS del paciente. Se debe gestionar
 traslado a casa en ambulancia no medicalizada (a cargo de la EPS) o vehículo destinado
para tal fin por la secretaria de salud, si el paciente no cuenta con vehículo particular
para su traslado o su familia y convivientes se encuentran en aislamiento preventivo.
23. En caso de egresar indicar incapacidad médica para reposo relativo y aislamiento
obligatorio en casa de 10 a 20 días contados a partir del inicio de los síntomas:
En caso de pacientes con síntomas leves a moderados: 10 a 14 días.
En caso de pacientes con síntomas severos: 20 días.
En caso de pacientes con inmunosupresión de base: 20 días.

En cuanto a lo relacionado con el reintegro social y laboral de casos con síntomas leves
a moderados, este se puede dar si se cumplen 3 requisitos:
- Aislamiento por un mínimo de 10 días contados a partir del inicio de los síntomas.
- Ausencia de fiebre por más de 24 a 72 h sin el uso de medicamentos antipiréticos.
- Mejoría de síntomas respiratorios (tos y disnea) o gastrointestinales (diarrea).
- No es necesario realizar control de detección de anticuerpos o prueba de rt-PCR /
PRDA, como un requisito para reincorporarse al trabajo.

Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. December 3, 2020

N Engl J Med 2020; 383:2291-2293. DOI: 10.1056/NEJMc2031364

Chanu Rhee, MD, MPH, Sanjat Kanjilal, Meghan Baker, MD, ScD, Michael Klompas, MD, MPH, Duration of
SARS-CoV-2 Infectivity: When is it Safe to Discontinue Isolation?. Clinical Infectious Diseases, ciaa1249,
https://doi.org/10.1093/cid/ciaa1249
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1249/5896916#.X0VyC-Zwiap.twitter

Singh D, et al. Viral RNA Shedding and Transmission Potential of Asymptomatic and Pauci-symptomatic
COVID-19 Patients, Open Forum Infectious Diseases, ofaa599, https://doi.org/10.1093/ofid/ofaa599

“We studied the pattern and duration of viral RNA shedding in 32 asymptomatic and 11 paucisymptomatic coronavirus disease 2019
(COVID-19) cases. Viral RNA shedding in exhaled breath progressively diminished and became negative after six days of a positive
reverse transcription polymerase chain reaction (RT-PCR) test. Therefore, the duration of isolation can be minimised to six days.”

Duration of Isolation and Precautions for Adults with COVID-19, Updated Oct. 19, 2020.
https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html
Duration of Isolation and Precautions for Adults with COVID-19, Updated July 17, 2020.
https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html?s=09

Criteria for Return to Work for Healthcare Personnel with Suspected or Confirmed COVID-19 (Interim
Guidance), Updated May 5, 2020.
https://www.cdc.gov/coronavirus/2019-ncov/hcp/return-to-work.html

ADENDO: ACTUALIZACIÓN CONSENSO 27/06/2020 CONSENSO COLOMBIANO DE ATENCIÓN,

DIAGNÓSTICO Y MANEJO DE LA INFECCIÓN POR SARS-COV-2/COVID-19 EN ESTABLECIMIENTOS DE
ATENCIÓN DE LA SALUD: RECOMENDACIONES BASADAS EN CONSENSO DE EXPERTOS E INFORMADAS EN
LA EVIDENCIA ACIN-IETS.
https://www.revistainfectio.org/index.php/infectio/article/view/895

LINEAMIENTOS PARA EL USO DE PRUEBAS MOLECULARES RT-PCR Y PRUEBAS DE ANTÍGENO Y

SEROLÓGICAS PARA SARS-CoV-2 (COVID-19) EN COLOMBIA, Código GIPS21, Versión 05.
https://www.minsalud.gov.co/Ministerio/Institucional/Procesos%20y%20procedimientos/
GIPS21.pdf

Se recomienda que los pacientes con infección SARS CoV-2/ COVID-19 pueden ser dados de alta
y continuar aislamiento en casa si cumplen los siguientes criterios:
► Ausencia de fiebre ≥ 24 horas sin antipiréticos
y
►Ausencia de dificultad respiratoria con saturación de oxígeno >90% al aire ambiente
por más de 48 horas sin alteraciones del ritmo cardíaco.
y
► No requiere hospitalización por otras patologías
y
► Tolerancia a la vía oral
24. Recomendaciones para el manejo de la LACTANCIA MATERNA si es del caso:
Se sugiere, en caso de no ser posible la extracción manual de la leche, el neonato sea
amamantado, teniendo en cuenta realizar una limpieza previa del área de las mamas y
pezones con jabón, y abundante agua, higienizar de manos previo a la lactancia y usar
mascarilla convencional por parte de la madre.
25. Se recomienda que el neonato asintomático hijo de madre sintomática, permanezca en
aislamiento de la madre en habitación individual con cuidador sano o de no disponer
del mismo, en la unidad neonatal, mientras cumple los cuidados rutinarios para el
egreso.
26. Recomendaciones adicionales egreso MADRE – RECIEN NACIDO: Se recomienda al
egreso continuar el aislamiento de la madre y el recién nacido por 28 días, con las
medidas indicadas de higiene de manos antes de tocar al recién nacido, o de extraerse
leche, uso permanente de mascarillas quirúrgicas estándar. Evitar hablar especialmente
durante el amamantamiento o extracción de la leche y mantener las medidas de
desinfección rutinaria de las superficies con las que entre en contacto.
27. En caso de realizarse un procedimiento generador de aerosoles, el personal no podrá
ingresar durante 3 a 4 horas después de la realización del procedimiento a menos que
ingrese con protección contra aerosoles.
28. Se recomienda el uso de equipo médico exclusivo para los casos sospechosos o
confirmados de infección por SARS CoV-2/COVID-19 (Fonendoscopio,
 esfigmomanómetro, termómetro) con desinfección posterior a cada uso.
29. Se recomienda que el familiar o cuidador del paciente con infección por SARS CoV-2 /
COVID-19 que cumpla criterios de acompañamiento debe ser único, sin comorbilidades
y menor de 60 años.
Diligenciar solicitud de consentimiento informado escrito para el acompañamiento de
pacientes con infección sospechada o confirmada por SARS CoV-2 / COVID-19.
30. Se recomienda restricción absoluta de visitas de familiares de pacientes infectados por
SARS CoV-2 / COVID-19 en las unidades de cuidado intensivo, servicios de urgencias y
servicios de hospitalización salvo en las siguientes situaciones:
► Pacientes pediátricos
► Pacientes adultos con dependencia o discapacidad que ameriten acompañante
permanente según criterio de los médicos tratantes.
La movilización del acompañante está absolutamente restringida.
31. Se recomienda en la institución donde fallece el paciente permitir un momento de
despedida a 1 o 2 familiares designados quienes no tengan factores de riesgo ni sean
mayores de 60 años, con los EPP apropiados (mascarilla quirúrgica, bata, guantes). No
se permitirá tocar al fallecido, debiéndose mantener la distancia de dos metros del
cuerpo y un tiempo de exposición inferior a 15 minutos.
En caso de pacientes que fallezcan dentro de los primeros 26 dias de la enfermedad con
respecto al inicio de los síntomas se deben seguir las orientaciones para el manejo, traslado
y disposición final de cadáveres por SARS-CoV-2
(COVID-19) -Versión 05 / Código GIPG08. MINISTERIO DE SALUD Y PROTECCIÓN SOCIAL. Bogotá,
junio de 2020.
https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/ED/VSP/manejo-cadaveres-covid-19f.pdf
Si el paciente fallece luego del dia 26 de enfermedad con respecto al inicio de los
síntomas el cadáver puede ser manejado sin las restricciones indicadas para COVID-19
ya que no se han documentado virus viables con cultivos positivos luego de 26 dias de
evolución de la enfermedad.
“Post mortem study: One study on alveolar specimens from 68 elderly deceased
reported postmortem studies on lung tissues from six cases were available for viral
isolation. The evaluation showed viable SARS-CoV-2 in all six cases - in one case on day
26 from symptom onset.”
Jefferson T, et al. Viral cultures for COVID-19 infectious potential assessment – a systematic
review, Clinical Infectious Diseases, ciaa1764. https://doi.org/10.1093/cid/ciaa1764

ANTIMICROBIANOS EMPIRICOS DIRIGIDOS CONTRA BACTERIAS ASOCIADAS A

NEUMONIA ADQUIRIDA EN LA COMUNIDAD.
Se recomienda terapia antibiótica empírica en los pacientes con sospecha de neumonía
bacteriana acorde a guías nacionales o guías institucionales.
No se deben indicar antibióticos de forma sistemática.
En caso de iniciar antimicrobianos se deben evaluar estudios microbiológicos solicitados
cada 24 h para definir la necesidad de continuar con estos o suspenderlos si es del caso.
Factores que sugieren coinfección bacteriana (al ingreso hospitalario):
Variables Características
Temperatura T>38.5© que persista por más de 72 h.
Síntomas Tos con expectoración mucopurulenta.
Hemograma Leucocitosis con neutrofilia.
Radiografía Consolidación lobar (especialmente en la primeras 2 semanas).
Tomografía
Comorbilidade Enfermedad renal crónica moderada a severa.
s 26 (44.1%) vs 423 (25.7%) OR 2.19 (IC 95%, 1.35-3.57) p 0.002
Presentación *Sepsis: 52 (88.1%) vs 1208 (73.4%) OR 2.55 (IC 95%, 1.28-5.08), p 0.008
clínica **Sepsis severa: 35 (59.3%) vs 446 (27.1%) OR 3.62 (IC 95%, 2.16-6.07),
p <.001
***Shock séptico: 17 (28.8%) vs 121 (7.4%) OR 4.60 (IC 95%, 2.65-8.00),
p <.001
Biomarcadores Proteína C Reactiva (PCR):
Biomarcador asociado con severidad y pronostico en COVID-19.
No es un biomarcador específico para coinfección bacteriana en COVID-19 teniendo
en cuenta relación con IL-6.
26.2 mg/dl (14.9-123.0) vs 18.5 mg/dl (7.1-90.0), p 0.15 (coinfección bacteriana vs
no coinfección bacteriana).
Procalcitonina (PCT):
Biomarcador asociado con severidad, pronostico y coinfección bacteriana en COVID-
19.
Punto de corte Interpretación
ng/ml
≤0.10 Es improbable la presencia de coinfección bacteriana
(VPN 98.3%).
<0.25 Muy bajo riesgo de coinfección bacteriana.
<0.50 Bajo riesgo de coinfección bacteriana
(>96% de los casos leves).
≥0.50 Alto riesgo de coinfección bacteriana y complicaciones
asociadas a COVID-19.
 -Coinfección bacteriana: 19 (55.9%) vs 186 (21.2%) OR 4.99 (IC
95%, 1.87-13.33) p 0.001, VPP 9.3% (coinfección bacteriana vs
no coinfección bacteriana).
-Complicaciones asociadas a COVID-19: OR 4.76; IC 95%, 2.74-
8.29
>1.0 Muy alto riesgo de coinfección bacteriana y complicaciones
asociadas a COVID-19.
PCT también se puede elevar en SDRA, compromiso renal severo, choque
cardiogénico y falla orgánica múltiple.
En caso de iniciar antibióticos por coinfección bacteriana, si PCT control disminuye a
<0.5 ng/ml y/o reducción es ≥ 80% con respecto a PCT basal, se debe evaluar la
posibilidad de suspender antimicrobianos.
Requiere MIPRES, CÓDIGO CUPS 906841.

“The role of procalcitonin in identifying community-associated bacterial infections among patients with
coronavirus disease 2019 is not yet established. In 2443 patients with 148 bacterial co-infections, mean
procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/mL,
p=0.0091) and with bacteremia (34.25 ± 85.01 ng/mL, p=0.0125) than without infection (2.00 ±15.26
ng/mL). Procalcitonin (cutoff 0.25 or 0.50 ng/mL) did not reliably identify bacterial co-infections, but
may be useful in excluding bacterial infection.”

May M, et al. Limited Utility of Procalcitonin in Identifying Community-Associated Bacterial

Infections in Patients Presenting with Coronavirus Disease 2019. Antimicrobial Agents and
Chemotherapy Jan 2021, AAC.02167-20; DOI: 10.1128/AAC.02167-20

Relación Ferritina ng/ml /Procalcitonina ng/ml ≥877:

- Neumonia COVID-19 Vs Neumonia Bacteriana.
- 4037.5 vs 802, p<0.001
- Sensibilidad 85% / Especificidad 56% / VPP 93.2% / LR 1.92
- OR: 11.27, CI: 4-31.2, p<0.001.

“Serum ferritin levels are unaffected by elevated plasma levels of acute-phase

inducing cytokines tumor necrosis factor-alpha (TNF) or Interleukin-6 (IL-6) in
healthy volunteers. The association of viral infection of cells with cytolysis and
liberation of intracellular ferritin into the blood is consistent with the substantial
elevation of blood ferritin reported in COVID-19 patients In contrast to COVID-19,
bacterial pathogenesis does not necessitate host cell lysis since most typical
bacterial pneumonia pathogens do not require intracellular invasion to replicate. We
believe it is useful to think of circulating ferritin as a biomarker indicating cytolysis
and suggest an analogy with circulating levels of cardiac isoenzymes (often Troponin
proteins) as indicators of cardiomyocyte lysis or damage.”
 Gharamti A, et al. Diagnostic utility of a Ferritin-to-Procalcitonin Ratio to
differentiate patients with COVID-19 from those with Bacterial Pneumonia: A
multicenter study, Open Forum Infectious Diseases, 2021; ofab124,
https://doi.org/10.1093/ofid/ofab124

Presepsina (PSP):
Biomarcador asociado con severidad, pronostico y coinfección bacteriana en COVID-
19.
Punto de corte Interpretación
pg/ ml
<250 Es improbable la presencia de coinfección bacteriana y
complicaciones asociadas a COVID-19.
<400 Bajo riesgo de coinfección bacteriana y complicaciones
asociadas a COVID-19.
≥800 Alto riesgo de coinfección bacteriana y complicaciones
asociadas a COVID-19.
≥1000 Muy alto riesgo de coinfección bacteriana y complicaciones
asociadas a COVID-19.
Requiere MIPRES, CÓDIGO CUPS 906850.

* Sepsis, deben cumplirse al menos dos de los siguientes criterios:

Temperatura >38°C o <36°C - Frecuencia cardiaca>90/min - Frecuencia respiratoria >20/min - Leucocitos >12000/L o <4000/L o
>10% cayados.
**Sepsis severa, sepsis asociada con disfunción de órganos:
Presión arterial sistólica <90 mm Hg - Lactato sérico >2 mmol/L - Plaquetas <100000/L - Bilirrubinas >2 mg/dL - Creatinina >2 mg/dL
-
Soporte ventilatorio.
***Shock séptico, sepsis severa con requerimiento de vasopresores.

Revisión de la literatura:
Langford BJ et al: “co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI
0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall
proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection
was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-
19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%).”

Rawson TM et al: “For COVID-19, 62/806 (8%) patients were reported as experiencing
bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of
broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary
analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy.”

Lansbury L, et al: “Thirty studies including 3834 patients were included. Overall, 7% of hospitalised
COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183). A higher proportion of ICU
patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, versus
4%, 95% CI 1-9). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and
Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014),
with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-
infections.”

Kim D, et al: “Of the 116 specimens positive for SARS-CoV-2, 24 (20.7%) were positive for 1 or more
additional pathogens, compared with 294 of the 1101 specimens (26.7%) negative for SARS-CoV-2
(difference, 6.0% [95% CI, –2.3% to 14.3%]). The most common co-infections were rhinovirus/enterovirus
(6.9%), respiratory syncytial virus (5.2%), and non–SARS-CoV-2 Coronaviridae (4.3%).”

Chen X, et al: “The report shows that when SARS-CoV-2 and influenza A virus were coinfected,
lymphocytes were increased, and C-reactive protein was often detected while the trend of lymphocytes
was the opposite of SARS-CoV-2 infection alone.”
“Zuo et al. (2020) analyzed the changes of fecal fungi in 30 Hong Kong COVID-19 patients during
hospitalization showed that compared with healthy controls, the pathogenic fungi such as Candida spp.
and Aspergillus spp. were significantly enriched in patients, and the intestinal fungal dysregulation could
be continued until 12 days after the patient’s nasopharyngeal sample was cleared of SARS-CoV-2.”
“Moreover, the bacterial and fungal coinfection was associated with a 2.5-fold increase in the risk of
death in SARS-CoV-2 (Martins-Filho et al. 2020) indicating that there is a certain interaction between
bacteria or fungi and SARS-CoV-2.”

Lehmann CJ, et al: “Co-infection was identified in 12 (3.7%) patients, 7 (1.2%) of which were bacterial
infections. Despite low frequency of co-infection, antibiotic use was high 222 (69%). Co-infection was
more frequent in patients admitted to the ICU 7/17 (41%, p<0.005) but not for non-survivors 2/22 (9%,
p=0.17).

Vaughn VM, et al: “In 38 Michigan hospitals, early empiric antibacterials were prescribed to 56.6% (965/1705) of
patients hospitalized with COVID-19 while 3.5% (59/1705) had a confirmed community onset bacterial co-infection.
Among hospitals, empiric antibacterial use varied from 27% to 84%.
Community-onset bacterial co-infections were confirmed in 3.5% (59/1705) of all patients, including 1.8% (31/1705)
who had a positive blood culture and 1.7% (29/1705) who had a bacterial respiratory pathogen identified (from
respiratory culture or non-culture diagnostic test). Community-onset bacterial infections occurred in 4.9% (47/965) of
patients who received early empiric antibacterial therapy vs. 1.6% (12/740) of those who did not (P<.001), of which
33.3% (4/12) were subsequently started on antibiotics. Patients were more likely to have a community-onset
bacterial infection if they were older, had a lower body mass index, had kidney disease, were admitted from a skilled
nursing facility, were more severely ill (e.g., admitted to intensive care), or had more signs of a bacterial infection
(e.g., higher white blood cell count).
Though 55.9% (19/34) of patients with a community-onset bacterial co-infection had a procalcitonin >0.5 ng/mL, so
did 21.2% (186/876) of those without a community-onset bacterial co-infection. Thus, the positive predictive value of
a procalcitonin >0.5 ng/mL was 9.3% for community-onset bacterial coinfection. In contrast, the negative predictive
value of a procalcitonin ≤0.1 ng/mL was 98.3%.
Compared to patients without a confirmed community-onset bacterial infection, those with a confirmed infection
had a longer length of stay (median 7 [IQR 4-10] vs. 5 days [3-8], P=0.003) and had higher in-hospital mortality (47.5%
[28/71] vs. 18.0% [297/1634], P<.001).
Nearly half (45.9%, 783/1705) of patients had respiratory PCR testing while only 0.5% (9/1705) had an identified
community-onset viral co-infection. There was no difference in early empiric antibiotic use in those with an identified
community-onset viral co-infection vs. those without (66.7% vs. 56.5%, P=0.74).
Of patients with COVID-19 who were prescribed empiric antibacterials and had their COVID19 test return before the
end of their hospitalization, 453/832 (54.4%) had their antibacterials stopped within 1 day after COVID-19 tests
returned positive. Of the 379 that had antibacterials continued, only 28 (7.4%) had a confirmed community-onset
bacterial coinfection.
For every patient we identified as having a bacterial infection, nearly 20 without an identified infection also received
empiric antibacterial therapy.”

Somers et al: “In an observational analysis by Somers et al of 154 patients with severe COVID-19 infection
requiring mechanical ventilation at Michigan Medicine: 40% developed a bacterial superinfection, with 32%
developing bacterial pneumonia. The median time to development of infection was 8-10 days after initiation of
mechanical ventilation.”

Zhou et al: “In the study of adult patients by Zhou et al:

15% of hospitalized COVID-19 patients developed a secondary bacterial infection (definition: clinical symptoms
or signs of pneumonia or bacteremia with a positive culture).
The median time to secondary bacterial infection was 17 days (13 to 19 days).
Of all COVID-19 patients in their cohort, 79% had a WBC <10000.
Only 1% of survivors developed a secondary bacterial infection, yet the median duration of fever in survivors
was 12 days and cough persisted for 19 days. Thus, ‘just in case’ treatment of bacterial infection can result in
prolonged durations of therapy.”

Khurana et al: “A total of 151 (13%) patients had secondary infections (56 -37% were ICU patients), and most got
infected within the first 14 days of hospital admission. Patients aged >50 years developed severe symptoms (p
0.0004) and/or had a fatal outcome (p 0.0005). The in-hospital mortality was observed in 50/151 (33%) COVID-19
patients with secondary infections. It was found to be statistically significant that in 24% of the total in-hospital
mortalities were attributable to a subsequent secondary infection. K. pneumoniae (33.3%) was the predominant
pathogen, followed by A. baumannii (27.1%). The overall resistance was up to 84%. Majority of the organisms were
multidrug-resistant (MDR) harbouring MDR genes.”
“The highest and lowest rates of secondary infections were found in patients aged between 38 and 60 years, and
below 20 years, respectively. Most co-infections occurred within the first two weeks of hospital admission, with an
average of 10.43 days.”
“Of the total 290 clinical samples, the most predominant were blood samples (126, 42.8%) followed by urine (62, 21.8%),
Endotracheal aspirate (ET)/Bronchoalveolar lavage (BAL) samples (53, 18.6%), pus (27, 9.1%), and others (22, 7.7%). Among the
bacterial (n 96) isolates, K. pneumoniae (32, 33.3%), was the most common organism, followed by A. baumannii (26, 27.1%), E. coli
(16, 16.7%), and P. aeruginosa (11, 11.5%).
Positive blood cultures were identified in 58/126 (46%) samples. Among these, K. pneumoniae and A. baumannii were the most
common isolates. Of the total 58 organisms isolated 19 were classified as contaminants; 12/19 (63%) Coagulase-negative
Staphylococcus aureus (CONS) (4/12 Methicillin-resistant MR-CONS, 8/12 Methicillin-sensitive MS-CONS).”
Significant growth was seen in 18/62 urine cultures, with Candida spp (9/18, 50%) being the predominant pathogen followed by P.
mirabilis in 3/18 (16.7%). Contaminants (a mixture of Gram-negative/positive organisms) /insignificant growth was seen in 24/62
(38%). A positive ET/BAL sample culture was found in 44/53 (83%) samples including endotracheal aspirates and bronchoalveolar
lavage samples, and 12/44 were classified as contaminants (a mixture of Gram-negative/positive organisms or upper respiratory
flora). K. pneumoniae and A. baumannii were the most commonly isolated pathogens.
From the sputum sample of one of the patients, Ascaris lumbricoides was also isolated.
Of the total 27 pus samples, 22 (81.5%) were culture positive, including 10 contaminants (a mixture of Gram-negative/positive
organisms). Escherichia coli (5/22, 23%) was the predominant organism isolated from pus samples.
Zaninotto M, et al: “PSP measurement during the hospitalization (from 2 to 7 days after admission)
demonstrated statistically significant higher values (Mann-Whitney test) in patients who died (median,
IQR = 1047, 763–1240; vs 417, 218–679 ng/L, p < 0.05) as well as in patients staying in ICU during all time
of hospitalization (median, IQR = 1069, 695–2299; vs 408, 202–660 ng/L, p < 0.001). According to ROC
curve analysis, the AUC of presepsin values in predicting mortality was 0.72 (p < 0.05). Furthermore, the
study of the relationship (Spearman correlation test) between PSP and different biochemical parameters
reflecting inflammation, has evidenced statistically significant but poor correlations with CRP (r = 0.59, p <
0.001), LDH (r = 0.52, p < 0.001) and stronger with PCT (r = 0.72, p < 0.001) values. Despite this
correlation, PCT showed values higher than 0.5 μg/L only in 2 out of 6 died patients (33%), and in 11 out
of 45 patients studied (24%).”

Khurana S, et al. Profile of co-infections & secondary infections in COVID-19 patients at a dedicated
COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance, Indian Journal
of Medical Microbiology, 2020. https://doi.org/10.1016/j.ijmmb.2020.10.014.

https://www.sciencedirect.com/science/article/pii/S0255085720300177
Claritromicina
- Dosis: 500 mg IV cada 12 h, diluir en 500 ml de Lactato de Ringer y pasar en perfusión
de 1 h, cuando las condiciones clínicas lo permitan considerar terapia secuencial oral
con 500 mg VO cada 12 h para completar 5 a 10 días de tratamiento según evolución.
- Precauciones: Se deben vigilar interacciones medicamentosas.
- Dosis en pacientes con disminución en la TFG:
30-60 ml/min Dosis sin cambios.
500 mg cada 12 h.
30-60 ml/min y uso Disminuir dosis en un 50%.
concomitante con Atazanavir 500 mg cada 24 h.
o Ritonavir.
< 30 ml/min Disminuir dosis en un 50%.
500 mg cada 24 h.
< 30 ml/min y uso Disminuir dosis en un 75%.
concomitante con Atazanavir 250 mg cada 24 h.
o Ritonavir.
Pacientes en diálisis Disminuir dosis en un 50%.
peritoneal 500 mg cada 24 h.
Pacientes en hemodiálisis Disminuir dosis en un 50%.
intermitente 500 mg cada 24 h.
Los días que corresponda sesión de hemodiálisis
administrar la dosis de Claritromicina al finalizar esta.
Pacientes en terapia de Dosis sin cambios.
reemplazo renal continuo 500 mg cada 12 h.
- Alternativa: Azitromicina 500 mg VO cada 24 h (en pacientes con intolerancia a
Claritromicina).
- Presentación disponible:
Claritromicina viales x 500 mg, tabletas x 500 mg, suspensión 250 mg/ 5 ml.
Azitromicina tabletas 500 mg, suspensión 200 mg/ 5 ml.

DOSIS DE MACROLIDOS PARA PACIENTES CON PESO MENOR A 40 KG:

Azitromicina: 26-35 kg: 300 mg VO día; 36-45 kg: 400 mg VO día; ≥ 46 kg: 500 mg VO día.
Claritromicina: 7.5 mg/kg IV/VO cada 12 horas (max: 500 mg/dosis).
Ceftriaxona
 - Dosis: 2 g IV cada 12 h por 2 dosis y luego continuar con 2 g IV cada 24 h para completar
5 a 10 días de tratamiento según evolución.
- Alternativa: Ampicilina Sulbactam 1,5 a 3 g IV cada 6 h.
- Situaciones especiales:
En caso de factores de riesgo para Pseudomona aeruginosa o bacilos gram negativos
resistentes considerar Cefepime 2 g IV cada 8 h (diluir en 100 a 250 ml de SSN y pasar
en perfusión de 1 a 4 h) o Piperacilina Tazobactam 4,5 g IV cada 6 h (diluir en 100 a 250
ml de SSN y pasar en perfusión de 1 a 4 h) para completar 7 a 10 días de tratamiento
según evolución.
- Presentación disponible:
Ceftriaxona viales x 1 g.
Ampicilina Sulbactam viales x 1,5 g.
Cefepime viales x 1 y 2 g.
Piperacilina Tazobactam viales x 4,5 g.
Referencias bibliograficas:
Dahal D, et al. Antimicrobial resistance during the COVID-19 pandemic: the missing patient
perspective, JAC-Antimicrobial Resistance, Volume 3, Issue 1, March 2021, dlab030,
https://doi.org/10.1093/jacamr/dlab030

Khurana S, et al. Profile of co-infections & secondary infections in COVID-19 patients at a

dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial
resistance, Indian Journal of Medical Microbiology, 2020.
https://doi.org/10.1016/j.ijmmb.2020.10.014.

https://www.sciencedirect.com/science/article/pii/S0255085720300177

Langford BJ et al., Bacterial co-infection and secondary infection in patients with COVID-19: a
living rapid review and meta-analysis, Clinical Microbiology and Infection.
https://doi.org/10.1016/j.cmi.2020.07.016

https://www.clinicalmicrobiologyandinfection.com/action/showPdf?pii=S1198-743X
%2820%2930423-7

Metlay JP, et al. Treatment of Community-Acquired Pneumonia During the Coronavirus Disease
2019 (COVID-19) Pandemic. Ideas and Opinions, 18 August 2020.
https://doi.org/10.7326/M20-2189

https://www.acpjournals.org/doi/pdf/10.7326/M20-2189

Rawson TM, et al. Bacterial and fungal co-infection in individuals with coronavirus: A rapid
review to support COVID-19 antimicrobial prescribing. Clinical Infectious Diseases, ciaa530,
https://doi.org/10.1093/cid/ciaa530

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa530/5828058

Lansbury L, et al. Co-infections in people with COVID-19: a systematic review and meta-analysis.
J Infect. 2020;81(2):266-275. doi: 10.1016/j.jinf.2020.05.046
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255350/

Kim D, et al. Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens.
JAMA. 2020;323(20):2085–2086. doi:10.1001/jama.2020.6266

https://jamanetwork.com/journals/jama/fullarticle/2764787

Orozco-Hernández JP, et al. (2020). Coinfección por SARS-CoV-2 y rinovirus-enterovirus en una

paciente adulta joven críticamente enferma en Colombia. Biomédica, 40(Supl. 2).
https://doi.org/10.7705/biomedica.5516

https://revistabiomedica.org/index.php/biomedica/article/view/5516

Chen, X., Liao, B., Cheng, L. et al. The microbial coinfection in COVID-19. Appl Microbiol
Biotechnol (2020). https://doi.org/10.1007/s00253-020-10814-6

https://link.springer.com/article/10.1007/s00253-020-10814-6#citeas
Lehmann CJ, et al. Community Acquired Co-infection in COVID-19: A Retrospective
Observational Experience, Clinical Infectious Diseases, ciaa902,
https://doi.org/10.1093/cid/ciaa902

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa902/5865452

Stochino C, et al. Clinical characteristics of COVID-19 and active tuberculosis co-infection in an

Italian reference hospital. Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.01708-
2020).

https://covidaba.com/wp-content/uploads/2020/06/Clinical-characteristics-of-COVID-19-and-
active-tuberculosis-co-infection-in-an-Italian-reference-hospital.pdf

Denggao P, et al. The role of procalcitonin in early differential diagnosis of suspected children
with COVID-19. medRxiv 2020.04.07.20057315;
doi: https://doi.org/10.1101/2020.04.07.20057315

https://www.medrxiv.org/content/10.1101/2020.04.07.20057315v3

Hays R, Pierce D, Giacomin P, Loukas A, Bourke P, McDermott R (2020) Helminth coinfection and
COVID-19: An alternate hypothesis. PLoS Negl Trop Dis 14(8): e0008628.
https://doi.org/10.1371/journal.pntd.0008628

https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008628

Chao-Ping Wu, et al. Recognition and management of respiratory coinfection and secondary
bacterial pneumonia in patients with COVID-19. Cleveland Clinic Journal of Medicine Jun 2020,
DOI: 10.3949/ccjm.87a.ccc015
https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc015

Benmalek R, et al. Bacterial co-infections and superinfections in COVID-19: a case report of right
heart infective endocarditis and literature review. Pan African Medical Journal. 2020;35(2):40.
[doi: 10.11604/pamj.supp.2020.35.2.23577]

https://www.panafrican-med-journal.com/content/series/35/2/40/full/

Fukada A, et al. (2020), Presepsin as a predictive biomarker of severity in COVID‐19: A case

series. J Med Virol. doi:10.1002/jmv.26164

https://onlinelibrary.wiley.com/action/showCitFormats?doi=10.1002%2Fjmv.26164

Zaninotto M, et al. Presepsin in risk stratification of SARS-CoV-2 patients. Clinica Chimica Acta
507 (2020) 161–163. https://doi.org/10.1016/j.cca.2020.04.020

https://www.sciencedirect.com/science/article/pii/S0009898120301753

Lippi G, et al (2020). Laboratory abnormalities in patients with COVID-2019 infection, Clinical

Chemistry and Laboratory Medicine (CCLM), 58(7), 1131-1134. doi:
https://doi.org/10.1515/cclm-2020-0198

https://www.degruyter.com/view/journals/cclm/58/7/article-p1131.xml

Vaughn VM, et al. Empiric Antibacterial Therapy and Community-onset Bacterial Co-infection in
Patients Hospitalized with COVID-19: A Multi-Hospital Cohort Study, Clinical Infectious Diseases,
ciaa1239, https://doi.org/10.1093/cid/ciaa1239

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1239/5895253

Somers EC, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19.

https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with
COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 11 [Online ahead of
print].

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

TERAPIA ANTIVIRAL EMPIRICA DIRIGIDA CONTRA INFLUENZA VIRUS A/B.

Se recomienda terapia antiviral empírica en los pacientes con sospecha de neumonía
por Influenza virus.
Se debe indagar sobre historia de vacunación contra Influenza virus 2020.
Oseltamivir
- Dosis: 75 mg VO cada 12 h durante 5 a 10 días según evolución.
- Presentación disponible: Capsulas x 75 mg.

Información complementaria:
“− PHE analysis of data from the latter part of the 2019-20 influenza season in England found
the risk of testing positive for SARS-CoV-2 was 68% lower among influenza positive cases,
suggesting possible pathogenic competition between the two viruses
− Patients infected with both viruses had a risk of death 5.92 (95% CI 3.21-10.91) times greater
than among those with neither influenza nor SARS-CoV-2, suggesting possible synergistic
effects in coinfected individuals.
− The odds of ICU admission, ventilator use or death was greatest among coinfected patients
when compared with patients with either SARS-CoV-2 or influenza infection.”

Clinical guide for the management of critical care for adults with COVID-19 during
the Coronavirus pandemic. Association of Anaesthetists, FICM, ICS, Royal College of
Anaesthetists. 28 October 2020, Version 4 | icmanaesthesiacovid-19.org

TERAPIA ANTIFUNGICA EN CASO DE ASPERGILOSIS PULMONAR O CANDIDIASIS

INVASIVA ASOCIADA A COVID-19
Despite all of the limitations previously given, the following statement can be made for critically ill patients with COVID-19: multiple
pulmonary nodules or lung cavitation should prompt thorough investigation for IPA, as they are rarely seen with COVID-19 alone
and have been described in a small proportion of patients with CAPA to date. Frequently observed radiological features of IPA, such
as the halo sign, are not sufficient to define CAPA without mycological evidence. This feature is insufficient because the halo sign
suggests local infarction, and an intrinsic part of severe COVID-19 is in-situ thrombosis due to endotheliopathy.
Galactomannan in bronchoalveolar lavage has been the main diagnostic test to diagnose secondary IPA in patients with severe
viral infection, although validation in patients with histologically confirmed COVID-19 is still scarce. Detection of galactomannan in
bronchoalveolar lavage does not prove tissue invasion, and the likelihood of infection is increased if circulating galactomannan is
detected. Unfortunately, the diagnostic yield of serum galactomannan is low in CAPA as, at best, 20% of patients showed positive
results, and proven CAPA cases have been reported with negative serum galactomannan.
TERAPIA ANTIVIRAL EMPIRICA DIRIGIDA CONTRA SARS-CoV-2.
Lopinavir/Ritonavir – Atazanavir/Ritonavir – Darunavir/Ritonavir
Evidencia actual no apoya el uso de inhibidores de la proteasa en pacientes con COVID-19:
- Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY)
Trial on lopinavir-ritonavir, 29 June 2020.
https://www.recoverytrial.net/news/no-clinical-benefit-from-use-of-lopinavir-ritonavir-in-hospitalised-
covid-19-patients-studied-in-recovery

- WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19.

https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-
ritonavir-treatment-arms-for-covid-19
Cloroquina o Hidroxicloroquina
Evidencia actual no apoya el uso de antimalaricos en pacientes con COVID-19:
- Tang W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019:
open label, randomised controlled trial. BMJ 2020; 369.
doi: https://doi.org/10.1136/bmj.m1849 (Published 14 May 2020).

- Mahévas M, et al. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require
oxygen: observational comparative study using routine care data. BMJ 2020; 369.
doi: https://doi.org/10.1136/bmj.m1844 (Published 14 May 2020).

- Rosenberg ES, et al. Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital
Mortality in Patients With COVID-19 in New York State. JAMA. Published online May 11, 2020.
doi:10.1001/jama.2020.8630.

- Qaseem A, et al. Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With
Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American
College of Physicians (Version 1). Ann Intern Med. 2020.
doi:10.7326/M20-1998.

- Mehra M, et al. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19:
a multinational registry analysis. www.thelancet.com. Published online May 22, 2020.
https://doi.org/10.1016/S0140-6736(20)31180-6.

- Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY)
Trial on hydroxychloroquine, 5 June 2020.
https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-
evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-
use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19

- Ladapo JA, et al. Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of
COVID-19 Infection, Hospitalization, and Death: Meta-Analysis. medRxiv 2020.09.30.20204693;
doi: https://doi.org/10.1101/2020.09.30.20204693
Plasma de convalecientes
Evidencia actual no apoya el uso de Plasma de convalecientes en pacientes con COVID-19:

- Janiaud P, et al. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With
COVID-19: A Systematic Review and Meta-analysis. JAMA. 2021;325(12):1185–1195.
doi: 10.1001/jama.2021.2747

- Trial Update: Recruitment for the CONCOR-1 trial is now complete.

https://concor1.ca/

- Simonovich VA, et al. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. NEJM,
 November 24, 2020. DOI: 10.1056/NEJMoa2031304
https://www.nejm.org/doi/full/10.1056/NEJMoa2031304

- Li L, Zhang W, Hu Y, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in

Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(5):460–
470. doi:10.1001/jama.2020.10044 https://jamanetwork.com/journals/jama/fullarticle/2766943?
guestAccessKey=d237da83-8a4a-43b6-877d-
f284137dce8b&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-
jama&utm_term=mostread&utm_content=olf-widget_08072020&s=03
Ivermectina
Evidencia actual no apoya el uso de Ivermectina en pacientes con COVID-19:

- Popular Drug Does Not Alleviate Mild Covid-19 Symptoms, Study Finds.
https://www.nytimes.com/2021/03/04/science/coronavirus-ivermectin-treatment.html?smid=tw-share

- Why You Should Not Use Ivermectin to Treat or Prevent COVID-19.

https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-treat-or-prevent-
covid-19?s=09

- López-Medina E, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild
COVID-19: A Randomized Clinical Trial. JAMA. Published online March 04, 2021. doi:
10.1001/jama.2021.3071

- Castañeda-Sabogal A, et al. Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and
meta-analysis. medRxiv 2021.01.26.21250420; doi: https://doi.org/10.1101/2021.01.26.21250420.

- The COVID-19 Treatment Guidelines Panel’s Statement on the Use of Ivermectin for the Treatment of
COVID-19. Last Updated: January 14, 2021. https://www.covid19treatmentguidelines.nih.gov/statement-
on-ivermectin/?s=09

- Chaccour C, et al. The effect of early treatment with ivermectin on viral load, symptoms and humoral
response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized
clinical trial, EClinicalMedicine (2021), https://doi.org/10.1016/j.eclinm.2020.100720

- Babalola OA, et al. Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised
controlled double blind dose response study in Lagos. medRxiv 2021.01.05.21249131; doi:
https://doi.org/10.1101/2021.01.05.21249131

- Advertencia: La ivermectina no debe ser usada para el tratamiento de COVID-19, OPS/OMS.

https://coronavirus.gob.mx/wp-content/uploads/2020/06/OPS_Declaracion_sobre_ivermectina_para_COVID-19.pdf

- Ivermectin is effective for COVID-19: meta analysis of 26 studies. Covid Analysis, November 26, 2020
(Version 6, December 16, 2020) @CovidAnalysis. https://ivmmeta.com/?
fbclid=IwAR3pm4r5ngYtEQ52OXcme4ZGDyWVinsKrZ_WM787-0A8edbpbqAfhFvQA8Y

- Soto-Becerra P, et al. Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among

hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a
nationwide Healthcare System in Peru. medRxiv 2020.10.06.20208066; doi:
https://doi.org/10.1101/2020.10.06.20208066

- Recomendación sobre el uso de ivermectina para el tratamiento de la COVID-19

https://iris.paho.org/bitstream/handle/10665.2/52379/OPSIMSCDECOVID-19200033_spa.pdf?
sequence=1&isAllowed=y

- López Reboiro M.L, et al. COVID-19 y Argumentum ad ignorantiam o «no todo vale». Revista Clínica
 Española, Available online 4 May 2020. https://doi.org/10.1016/j.rce.2020.04.013
https://www.sciencedirect.com/science/article/pii/S0014256520301223?via%3Dihub

- Schmith V. D, et al. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of
COVID‐19. Clinical Pharmacology & Therapeutics. https://doi.org/10.1002/cpt.1889
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.1889

- Mohiuddin ABT, et al. A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin

therapy on COVID19 patients. DOI: https://doi.org/10.21203/rs.3.rs-38896/v1

- Mudatsir M, et al. Antiviral Activity of Ivermectin Against SARS-CoV-2: An Old-Fashioned Dog with a New
Trick—A Literature Review. Sci. Pharm. 2020, 88, 36; doi:10.3390/scipharm88030036

Nitazoxanida
Evidencia actual no apoya el uso de Nitazoxanida en pacientes con COVID-19:

Rocco PM, et al. Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial. European
Respiratory Journal Jan 2020, 2003725; DOI: 10.1183/13993003.03725-2020

Kelleni MT. Nitazoxanide/azithromycin combination for COVID-19: A suggested new protocol for early Management.
Pharmacological Research 157 (2020) 104874. https://doi.org/10.1016/j.phrs.2020.104874

Mahmoud DB, et al. Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?. J Genet Eng
Biotechnol. 2020 Dec; 18: 35. Published online 2020 Jul 28. doi: 10.1186/s43141-020-00055-5

Martins-Filho PL, et al. Potential role for nitazoxanide in treating SARS-CoV-2 infection. Am J Physiol Lung Cell Mol
Physiol 319: L35–L36, 2020; doi:10.1152/ajplung.00170.2020.

Khatri M, et al. Nitazoxanide/Camostat combination for COVID-19: An unexplored potential therapy. Chem. Biol. Lett.
2020, 7(3), 192‐196. http://pubs.iscience.in/journal/index.php/cbl/article/view/1085

Azitromicina o Doxiciclina.
Evidencia actual no apoya el uso de Azitromicina o Doxiciclina en pacientes con COVID-19:

Chalmers JD, et al. Management of hospitalised adults with coronavirus disease-19 (COVID-19): A European
Respiratory Society living guideline. European Respiratory Journal Jan 2021, 2100048; DOI: 10.1183/13993003.00048-
2021
https://erj.ersjournals.com/content/early/2021/03/07/13993003.00048-2021

Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical
course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Published: March 04,
2021. DOI: https://doi.org/10.1016/S0140-6736(21)00461-X

PRINCIPLE trial finds no benefit from antibiotics, azithromycin and doxycycline for COVID-19 patients.
https://www.nihr.ac.uk/news/principle-trial-finds-no-benefit-for-antibiotics-azithromycin-and-doxycycline-for-covid-
19-patients/26680?s=09

RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19. Statement from the Chief
Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on azithromycin, 14 December
2020. https://www.recoverytrial.net/news/recovery-trial-finds-no-benefit-from-azithromycin-in-patients-
hospitalised-with-covid-19?s=09

Horby PW, et al. Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-
label, platform trial. medRxiv 2020.12.10.20245944. doi: https://doi.org/10.1101/2020.12.10.20245944
Furtado, R. H. M., et al (2020). Azithromycin in addition to standard of care versus standard of care alone in the
treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical
trial. The Lancet. doi:10.1016/s0140-6736(20)31862-6.

Oldenburg, C. E., & Doan, T. (2020). Azithromycin for severe COVID-19. The Lancet. doi:10.1016/s0140-
6736(20)31863-8.

Fiolet, T., et al. (2020). Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19
patients: a systematic review and meta-analysis. Clinical Microbiology and Infection. doi: 10.1016/j.cmi.2020.08.022.

Rodríguez-Molinero A, et al. (2020) Observational study of azithromycin in hospitalized patients with COVID-19. PLoS
ONE 15(9): e0238681. https://doi.org/10.1371/journal.pone.0238681.

Cavalcanti AB, et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. NEJM July 23,
2020. DOI: 10.1056/NEJMoa2019014.

Inmunoglobulina Intravenosa
Evidencia actual no apoya el uso de IGIV en pacientes con COVID-19:

Accini JL, et al. Actualización de la Declaración de consenso en medicina critica para la atención multidisciplinaria del paciente con
sospecha o confirmación diagnóstica de COVID-19 [Updated Consensus statement on critical medicine for the multidisciplinary care
of the patient with a suspected or confirmed diagnosis of COVID-19]. Acta Colombiana de Cuidado Intensivo. 2020; 20:1-112. doi:
10.1016/j.acci.2020.09.004

Famotidina – Inhibidor SARSCoV-2 papain-like protease (PLpro) / protease (3CLpro).

Evidencia actual no apoya el uso de Famotidina en pacientes con COVID-19:

https://www.idsociety.org/globalassets/idsa/practice-guidelines/covid-19/treatment/idsa-
covid-19-gl-tx-and-mgmt-v3.3.0.pdf

Yeramaneni S, et al. Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158
Hospitalized Patients With Coronavirus Disease 2019 From a Large Healthcare System. Gastroenterology 2021; 160:
919–921. DOI: https://doi.org/10.1053/j.gastro.2020.10.011

Remdesivir - No disponibilidad en Colombia.

Estudio solidaridad no reporto beneficios en mortalidad, requerimiento de ventilación mecánica o estancia

hospitalaria (estudio controlado – aleatorizado), n: 11330 pacientes, Remdesivir 2750 pacientes.
Estudio ACTT-1 reporto disminución de la progresión de pacientes con requerimiento de oxigeno a ventilación
mecánica o ECMO (estudio controlado – aleatorizado), n: 1062 pacientes (Remdesivir 13% vs. Placebo 23%; IC 95%, -
15 to -4), no se demostró reducción en mortalidad al dia 29 (Remdesivir 11.4% vs. Placebo 15.2%; OR 0.73 [IC 95%
0.52-1.03]; p=0.07).

Consenso Europeo no recomienda el uso de Remdesivir en pacientes con COVID-19 que requieran ventilación
mecánica.
Chalmers JD, et al. Management of hospitalised adults with coronavirus disease-19 (COVID-19): A European
Respiratory Society living guideline. European Respiratory Journal Jan 2021, 2100048; DOI: 10.1183/13993003.00048-
2021
https://erj.ersjournals.com/content/early/2021/03/07/13993003.00048-2021

No se encontro beneficio adicional con Tocilizumab o el anticuerpo monoclonal LY-CoV555.

Roche provides update on the phase III REMDACTA trial of Actemra/RoActemra plus Veklury in patients with severe
COVID-19 pneumonia.
The REMDACTA clinical trial of Actemra/RoActemra plus Veklury did not meet its primary endpoint of improved time
to hospital discharge for patients with severe COVID-19 pneumonia or its key secondary endpoints compared to
Veklury alone.
https://www.roche.com/media/releases/med-cor-2021-03-11.htm?s=03

“Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among
hospitalized patients who had Covid-19 without end-organ failure.”

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19 - ACTIV-3/TICO LY-CoV555 Study Group.
March 11, 2021. N Engl J Med 2021; 384:905-914. DOI: 10.1056/NEJMoa2033130

Referencias bibliográficas:

Touafchia A, et al. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety
concerns, Clinical Microbiology and Infection, https://doi.org/10.1016/j.cmi.2021.02.013

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19 List of authors.
ACTIV-3/TICO LY-CoV555 Study Group. December 22, 2020.
DOI: 10.1056/NEJMoa2033130

“Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy
among hospitalized patients who had Covid-19 without end-organ failure”

WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial
Results. December 2, 2020. DOI: 10.1056/NEJMoa2023184

“At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive
remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including
651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through
treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8;
interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was
already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients
receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI],
0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its
control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146
of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients
receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11).
No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or
hospitalization duration.”

U.S. Food and Drug Administration Approves Gilead’s Antiviral Veklury® (remdesivir) for Treatment of
COVID-19. https://www.gilead.com/news-and-press/press-room/press-releases/2020/10/us-food-and-
drug-administration-approves-gileads-antiviral-veklury-remdesivir-for-treatment-of-covid19

Pan H, et al. Repurposed antiviral drugs for COVID-19 –interim WHO SOLIDARITY trial results
WHO Solidarity trial consortium, medRxiv 2020.10.15.20209817; doi:
https://doi.org/10.1101/2020.10.15.20209817

“In 405 hospitals in 30 countries 11,266 adults were randomized, with 2750 allocated Remdesivir, 954
Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study
drug. Compliance was 94-96% midway through treatment, with 2-6% crossover. 1253 deaths were reported
(at median day 8, IQR 4-14). Kaplan-Meier 28-day mortality was 12% (39% if already ventilated at
randomization, 10% otherwise). Death rate ratios (with 95% CIs and numbers dead/randomized, each drug
vs its control) were: Remdesivir RR=0.95 (0.81-1.11, p=0.50; 301/2743 active vs 303/2708 control),
Hydroxychloroquine RR=1.19 (0.89-1.59, p=0.23; 104/947 vs 84/906), Lopinavir RR=1.00 (0.79-1.25, p=0.97;
148/1399 vs 146/1372) and Interferon RR=1.16 (0.96-1.39, p=0.11; 243/2050 vs 216/2050). No study drug
definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics),
initiation of ventilation or hospitalisation duration.”

Burwick RM, et al. Compassionate Use of Remdesivir in Pregnant Women with Severe Covid-19, Clinical
Infectious Diseases, ciaa1466, https://doi.org/10.1093/cid/ciaa1466

Maldarelli GC, et al. Remdesivir Treatment for Severe COVID-19 in Third-Trimester Pregnancy: Case Report
and Management Discussion, Open Forum Infectious Diseases, Volume 7, Issue 9, September 2020,
ofaa345, https://doi.org/10.1093/ofid/ofaa345

Beigel JH, et al. Remdesivir for the Treatment of Covid-19 — Final Report. October 8, 2020. DOI:
10.1056/NEJMoa2007764
 1. Sub-group “n” values add up to 1,051 instead of 1,062 because 11 Patients did not have a severity baseline
score recorded
2. Clinical Status was a pre-specified key secondary endpoint, and disease progression was a pre-specified
secondary endpoint
3. From 15 days to 10 days, an increased recovery rate of 29% compared with placebo; rate ratio for recovery
1.29; 95% CI 1.12-1.49; p<0.001
4. From 18 days to 11 days; rate ratio 1.31; 95% CI 1.12-1.52; severe disease was defined as requiring
mechanical ventilation, requiring oxygen, a SpO2 ≤ 94% on room air, or tachypnea (respiratory rate ≥24
breaths/min)
5. Incidence of new use of oxygen (36% remdesivir vs. 44% in placebo), new high-flow oxygen (17%
remdesivir vs. 24% placebo), and new mechanical ventilation or ECMO (13% remdesivir vs. 23% placebo)
were all lower in those patients treated with remdesivir compared with placebo
6. Compared with placebo, remdesivir treatment effect was maintained at Day 15 through Day 29 (OR: 1.50;
95% CI 1.2-1.9; P<0.001)
7. 11.4% mortality in patients treated with remdesivir vs. 15.2% with placebo at Day 29; HR 0.73 [95% CI
0.52-1.03]; p=0.07
8. Post-hoc sub-group analysis performed across all sub-groups (not accounting for multiplicity); 70%
reduction in mortality compared with placebo (HR 0.30 [95% CI 0.14-0.64]); remdesivir treatment group
n=232, placebo group n=203

In the randomized, double-blind, placebo-controlled ACTT-1 trial, Remdesivir significantly improved time to recovery
as compared to placebo – by five days in the overall study population (10 vs. 15 days; rate ratio, 1.29; 95% CI, 1.12 to
1.49; p<0.001) and seven days in patients who required oxygen support at baseline (11 vs. 18 days; rate ratio, 1.31;
95% CI, 1.12 to 1.52). As a secondary endpoint, Remdesivir also reduced disease progression in patients needing
oxygen, resulting in a significantly lower incidence of new mechanical ventilation or ECMO (13% vs. 23%; 95% CI, -15
to -4). In the overall patient population, there was a trend toward reduced mortality with Remdesivir compared with
placebo at Day 29 (11.4% vs. 15.2%, HR 0.73; 95% CI, 0.52 to 1.03).

The ACTT-1 trial results are complemented by results of two Phase 3 open-label trials of Remdesivir conducted in
adult patients with severe and moderate COVID-19. The SIMPLE-Severe trial, conducted in hospitalized patients who
required supplemental oxygen and who were not mechanically ventilated, found that a five-day or a 10-day
treatment course of Veklury achieved similar clinical outcomes (odds ratio 0.75; 95% CI, 0.51 to 1.12). The SIMPLE-
Moderate trial, conducted in hospitalized patients who did not require supplemental oxygen, showed statistically
improved clinical outcomes with a five-day treatment course of Remdesivir compared with standard of care (odds
ratio 1.65; 95% CI, 1.09 to 2.48; p=0.017). The odds of improvement in clinical status with the 10-day treatment
course of Remdesivir versus standard of care were also favorable, trending toward but not reaching statistical
significance (odds ratio 1.31; 95% CI, 0.88 to 1.95).

The incidence of adverse events associated with Remdesivir was similar to placebo in the ACTT-1 trial. Rates of
serious adverse events (SAEs) were numerically higher in the placebo group compared with the Remdesivir group.
Treatment discontinuation, all-cause grade 3 and 4 adverse events (AEs) and laboratory abnormalities were similar
across groups. In the SIMPLE-Severe trial, the most common adverse reactions occurring in at least 5% of subjects in
either the Remdesivir 5-day or 10-day group, respectively, were nausea (5% vs 3%), AST increased (3% vs 6%), and
ALT increased (2% vs 7%). In the SIMPLE-Moderate trial, the most common adverse reaction occurring in at least 5%
of subjects in the Remdesivir groups was nausea (7% in the 5-day group, 4% in the 10-day group).

Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-
controlled, multicentre trial. Lancet 2020; 395(10236): 1569-78.

Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med 2020.

Spinner CD, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate
COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(11):1048–1057. doi:10.1001/jama.2020.16349

Bhimraj A, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients
with COVID-19. Published by IDSA on 4/11/2020. Last updated, 9/25/2020.
https://www.idsociety.org/globalassets/idsa/practice-guidelines/covid-19/treatment/idsa-covid-19-gl-tx-and-mgmt-
v3.3.0.pdf

PROTOCOLO FARMACOCLÍNICO DEL USO DE REMDESIVIR (VEKLURY®) EN EL TRATAMIENTO DE LA ENFERMEDAD POR

COVID-19 EN EL SISTEMA NACIONAL DE SALUD. DIRECCIÓN GENERAL DE CARTERA COMÚN DE SERVICIOS DEL SNS Y
FARMACIA. Aprobado por la Comisión Permanente de Farmacia 08/09/2020.
https://www.mscbs.gob.es/profesionales/farmacia/valtermed/docs/
20200908_Protocolo_farmacoclinico_remdesivir2.pdf

REMDESIVIR TREATMENT PROTOCOL. NHS 22/09/2020.

https://www.uhb.nhs.uk/coronavirus-staff/clinical-info-pathways/clinical-info-pathways-downloads/c138-remdesivir-
treatment-protocol.pdf

Rochwerg B, et al. Remdesivir for severe covid-19: a clinical practice guideline. BMJ 2020; 370:m2924.
doi: https://doi.org/10.1136/bmj.m2924 (Published 30 July 2020).

Gebrie D, et al. Efficacy of remdesivir in patients with COVID-19: a protocol for systematic review and meta-analysis
of randomised controlled trials. BMJ Open 2020; 10: e039159. doi:10.1136/bmjopen-2020-039159

Halimi V, et al. The use of remdesivir outside of clinical trials during the COVID-19 pandemic. J of Pharm Policy and
Pract 13, 61 (2020). https://doi.org/10.1186/s40545-020-00258-8

Gonzales-Zamora JA, et al. Successful treatment with Remdesivir and corticosteroids in a patient with COVID-19-
associated pneumonia: A case report. Medwave 2020; 20(7): e7998 doi: 10.5867/medwave.2020.07.7998

Hospital Wide. Version 1.8 REMDESIVIR ACCESS PROGRAMS 06/17/2020.

https://www.chkd.org/uploadedFiles/Documents/COVID-19/remdesivir%20CHKD%20guideline%204-3.pdf

Carothers C, Birrer K, Vo M. Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in
COVID-19: a case series [published online October 2, 2020]. Pharmacotherapy. doi: 10.1002/PHAR.2464.

INTERIM CLINICAL GUIDANCE FOR ADULTS WITH SUSPECTED OR CONFIRMED COVID-19 IN BELGIUM.
18 September 2020; Version 13. Amendments on the 22 September 2020.
https://covid-19.sciensano.be/sites/default/files/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf

COVID-19 Scientific Advisory Group Rapid Response Brief. Key Research Question: What is the evidence for
effectiveness of Remdesivir as a treatment for COVID-19 disease?
https://www.albertahealthservices.ca/assets/info/ppih/if-ppih-covid-19-sag-effectiveness-of-remdesivir-rapid-
review.pdf

Remdesivir for treating hospitalised patients with suspected or confirmed COVID-19. Evidence review: COVID-19:
Remdesivir (June 2020) – NICE.
https://www.nice.org.uk/advice/es27/evidence/evidence-review-pdf-8771329261

INPATIENT GUIDANCE FOR TREATMENT OF COVID-19 IN ADULTS AND CHILDREN. Michigan Medicine – University of
Michigan. https://www.med.umich.edu/asp/pdf/adult_guidelines/COVID-19-treatment.pdf

State of West Virginia Remdesivir Protocol for Use of West Virginia’s Allocation of Remdesivir Solution for Injection
(Version 1). West Virginia Remdesivir Protocol (Version 1); May 15, 2020.
https://growthzonesitesprod.azureedge.net/wp-content/uploads/sites/861/2020/05/WV-Remdesivir-Protocol-
Version-1.0-05152020.pdf

Frediansyah A, et al. Remdesivir and its antiviral activity against COVID-19: A systematic review. Clinical Epidemiology
and Global Health, Available online 7 August 2020. https://doi.org/10.1016/j.cegh.2020.07.011

CLINICAL MANAGEMENT PROTOCOL: COVID-19. Government of India - Ministry of Health and Family Welfare
Directorate General of Health Services (EMR Division) - Version 5 - 03.07.20.
https://www.mohfw.gov.in/pdf/UpdatedClinicalManagementProtocolforCOVID19dated03072020.pdf

Favipiravir
Evidencia actual no apoya el uso de Favipravir en pacientes con COVID-19:

Agrawal U et al., Favipiravir: A new and emerging antiviral option in COVID-19, Medical Journal Armed Forces India,
https://doi.org/10.1016/j.mjafi.2020.08.004

Kaptein SJF, et al. Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas
hydroxychloroquine lacks activity. Proceedings of the National Academy of Sciences Oct 2020, 202014441; DOI:
10.1073/pnas.2014441117

Takahashi H, et al. Case studies of SARS-CoV-2 treated with favipiravir among patients in critical or severe condition.
International Journal of Infectious Diseases 100 (2020) 283–285. DOI:https://doi.org/10.1016/j.ijid.2020.08.047

Molnupiravir: Estudios en fase II/III.

https://www.dw.com/es/estudio-f%C3%A1rmaco-antiviral-molnupiravir-bloquea-la-transmisi%C3%B3n-del-covid-19-
en-24-horas/a-55858724

Cox RM, et al. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2
transmission in ferrets. Nat Microbiol 6, 11–18 (2021). https://doi.org/10.1038/s41564-020-00835-2

Maraviroc
Evidencia actual no apoya el uso de Maraviroc en pacientes con COVID-19:

Risner KH, et al. Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture.
bioRxiv 2020.08.12.246389; doi: https://doi.org/10.1101/2020.08.12.246389

TERAPIA ANTI-INFLAMATORIA
Se recomiendan dosis bajas de esteroides sistémicos en casos de pacientes con SaO2<93% o
que requieran suplencia de Oxigeno.
NO SE DEBEN UTILIZAR ESTEROIDES EN PACIENTES SIN REQUERIMIENTO DE OXIGENO.
Dexametasona
- Dosis: 6 mg/día IV o VO durante 6 a 10 días según evolución (en pacientes menores de
 40 kg, 0.15 mg/kg/día IV o VO).
Ajustar dosis según peso del paciente:
80-100 kg: 8 mg día.
>100 kg: 10 mg día.
- Alternativas en casos de no poder utilizar Dexametasona (hipersensibilidad o efectos
adversos):
Metilprednisolona 32-40 mg/día IV o VO, fraccionar cada 12-24 horas, (en pacientes
menores de 40 kg, 0.8 mg/kg IV día).
Hidrocortisona 50 mg cada 6-8 h IV, (en pacientes menores de 40 kg, 1 mg/kg q 12 h IV).
Prednisona 40-50 mg/día VO, fraccionar cada 12-24 horas, (en pacientes menores de 40
kg, 1 mg/kg/día VO).

Corticosteroids Other Than Dexamethasone:

If dexamethasone is not available, alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone
can be used.
For these drugs, the total daily dose equivalencies to dexamethasone 6 mg (oral or intravenous [IV]) are:
Prednisone 40 mg - Methylprednisolone 32 mg - Hydrocortisone 160 mg.
Long-acting corticosteroid: dexamethasone; half-life: 36 to 72 hours, administer once daily.
Intermediate-acting corticosteroids: prednisone and methylprednisolone; half-life: 12 to 36 hours, administer once daily
or in two divided doses daily.
Short-acting corticosteroid: hydrocortisone; half-life: 8 to 12 hours, administer in two to four divided doses daily.
Dexamethasone is a moderate cytochrome P450 (CYP) 3A4 inducer.
https://www.covid19treatmentguidelines.nih.gov/immunomodulators/corticosteroids/

- Precaución:
1. Se debe indicar profilaxis Estrongiloidiasis (síndrome de hiperinfestación) con
Ivermectina solución 0.6% a dosis de 200 ug/kg/día VO por 1 a 2 días (1 gota/kg/día
VO por 1 a 2 días) en pacientes procedentes de zonas rurales o zonas urbanas con
deficiencias higiénicas y sanitarias o en pacientes con eosinofilia al ingreso
hospitalario; las contraindicaciones para el uso de Ivermectina son: Embarazo,
Lactancia, Edad menor de 1 año, y peso menor de 15 kg; no se recomienda el uso de
Albendazol como alternativa a la Ivermectina teniendo en cuenta estudios que
demuestran menor eficacia.
2. Se debe descartar neumonía por Influenza virus teniendo en cuenta aumento de
mortalidad relacionada con el uso de esteroides sistémicos.
- Presentación disponible:
Dexametasona Viales x 4 mg y 8 mg / Tabletas x 0,75 mg y 4 mg; no requiere MIPRES.
Metilprednisolona viales x 500 mg / Tabletas x 4 mg y 16 mg; no requiere MIPRES.
Hidrocortisona viales x 100 mg; no requiere MIPRES.
Prednisolona tabletas x 5 (metabolito activo) – Prednisona tabletas x 50 mg
(profármaco); no requiere MIPRES.
Ivermectina solución oral 0,6%, frasco x 5 ml (150 gotas); requiere MIPRES.
- Referencias bibliograficas:
A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive
usual care. Overall, 482 patients (22.9%) in the dexamethasone group and
1110 patients (25.7%) in the usual care group died within 28 days after randomization
(age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93;
P<0.001). The proportional and absolute between-group differences in mortality
varied considerably according to the level of respiratory support that the patients
were receiving at the time of randomization. In the dexamethasone group, the
incidence of death was lower than that in the usual care group among patients
receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95%
CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical
ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among
 those who were receiving no respiratory support at randomization (17.8% vs. 14.0%;
rate ratio, 1.19; 95% CI, 0.92 to 1.55).

The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19.

February 25, 2021. N Engl J Med 2021; 384:693-704.
DOI: 10.1056/NEJMoa2021436

196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the
previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold
for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20
fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25
fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical
ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical
ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3
days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15
fewer per 1000, 30 fewer to 6 more, low certainty).
Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty),
mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical
ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and
most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes,
including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000,
110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low
certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of
death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions
was low or very low.

Siemieniuk R A, et al. Drug treatments for covid-19: living systematic review and network meta-
analysis BMJ 2020; 370: m2980. doi:10.1136/bmj.m2980

https://www.jwatch.org/na53062/2021/01/28/who-should-get-steroids-covid-19?
ijkey=P3mi2dtI4

Chaccour C, et al. The effect of early treatment with ivermectin on viral load, symptoms and humoral
response inpatients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized
clinical trial, EClinicalMedicine (2021), https://doi.org/10.1016/j.eclinm.2020.100720EClinicalMedicine 000
(2021) 100720Contents lists available atScienceDirectEClinicalMedicinejournal
homepage:https://www.journals.elsevier.com/eclinicalmedicine

“A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with
data
from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day
mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000
patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease
(moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast,
Systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty
evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic
corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be
minor (indirect evidence).”

“Timing—The timing of therapy from onset of symptoms was discussed by the panel. The RECOVERY
investigators reported a subgroup analysis suggesting that the initiation of therapy seven days or more
after symptom onset may be more beneficial than treatment initiated within seven days of symptom onset.
A post hoc subgroup analysis within the prospective meta-analysis did not support this hypothesis. While
some panel members believed that postponing systemic corticosteroids until after viral replication is
contained by the immune system may be reasonable, many noted that, in practice, it is often impossible to
ascertain symptom onset and that signs of severity often appear late (that is, denote a co-linearity between
severity and timing). The panel concluded that, given the evidence, it was preferable to err on the side of
administering corticosteroids when treating patients with severe or critical covid-19 (even if within 7
days of symptoms onset) and to err on the side of not giving corticosteroids when treating patients with
non-severe disease (even if after 7 days of symptoms onset).”

Lamontagne F, et al. Practice Update to living WHO guideline on drugs for covid-19. BMJ 2020; 371 doi:
https://doi.org/10.1136/bmj.m4475 (Published 20 November 2020)

https://www.bmj.com/content/371/bmj.m4475

Arabi, Y.M., Chrousos, G.P. & Meduri, G.U. The ten reasons why corticosteroid therapy reduces mortality in
severe COVID-19. Intensive Care Med (2020). https://doi.org/10.1007/s00134-020-06223-y

https://link.springer.com/article/10.1007/s00134-020-06223-y

Dequin P, Heming N, Meziani F, et al. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support
Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. Published online September
02, 2020. doi:10.1001/jama.2020.16761

https://jamanetwork.com/journals/jama/fullarticle/2770276

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between
Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A
Meta-analysis. JAMA. Published online September 02, 2020. doi:10.1001/jama.2020.17023

https://jamanetwork.com/journals/jama/fullarticle/2770279

Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY)
Trial on dexamethasone, 16 June 2020.

https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_v2final.pdf

Boggild AK, et al. on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT). CATMAT
statement on disseminated strongyloidiasis: Prevention, assessment and management guidelines. Can
Comm Dis Rep 2016; 42:12-19. https://doi.org/10.14745/ccdr.v42i01a03

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864421/pdf/CCDR-42-012.pdf

Fardet L, et al. Severe strongyloidiasis in corticosteroid-treated patients. Clinical Microbiology and Infection.
Volume 12, Issue 10, October 2006, Pages 945-947.
https://www.sciencedirect.com/science/article/pii/S1198743X1462022X

Henriquez‐Camacho C, et al. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis

infection. Cochrane Database of Systematic Reviews 2016, Issue 1. Art. No.: CD007745.
DOI: 10.1002/14651858.CD007745.pub3
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007745.pub3/full

Vasquez-Rios G, et al. Strongyloides stercoralis infection after the use of emergency corticosteroids: a case
report on hyperinfection syndrome. J Med Case Reports 13, 121 (2019). https://doi.org/10.1186/s13256-
019-2022-y
https://link.springer.com/content/pdf/10.1186/s13256-019-2022-y.pdf

Hailu T, et al. Efficacy of Single Dose Ivermectin Against Strongyloides stercoralis Infection Among Primary
School Children in Amhara National Regional State. Infect Dis (Auckl). 2020; 13: 1178633720932544. doi:
 10.1177/1178633720932544
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297470/

Thomas MC, Costello SA. Disseminated strongyloidiasis arising from a single dose of dexamethasone before
stereotactic radiosurgery. Int J Clin Pract. 1998;52(7):520-521.
https://pubmed.ncbi.nlm.nih.gov/10622101/

Buonfrate D, Gobbi F Treatment for chronic Strongyloides stercoralis infection: moderate-to-low evidence

shows that ivermectin is more effective and tolerable than albendazole and thiabendazole, respectively
BMJ Evidence-Based Medicine 2016; 21:102.

https://ebm.bmj.com/content/21/3/102

Perlas Clínicas. Controversias: Esteroides y desparasitación ¿una estrategia válida para todos los pacientes?

https://extension.medicinaudea.co/index.php/programas/item/307-controversias-esteroides-y-
desparasitacion

En caso de pacientes con contraindicaciones para el uso de esteroides se recomienda

evaluar la posibilidad de Baricitinib (Inhibidor quinasa Janus) 4 mg via oral cada 24 h por
14 días (o hasta egreso hospitalario) mas Remdesivir IV.

Infectious Diseases Society of America Guidelines on the Treatment and Management

of Patients with COVID-19 Published by IDSA on 4/11/2020. Last updated, 2/10/2021.

https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-
management/

“Double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized

adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or
placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical
status at day 15.
A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to
control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval
[CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01
to 1.32; P=0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI,
1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to
recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51;
95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control
group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the
combination group than in the control group (16.0% vs. 21.0%; difference, −5.0 percentage points; 95% CI,
−9.8 to −0.3; P=0.03), as were new infections (5.9% vs. 11.2%; difference, −5.3 percentage points; 95% CI,
−8.7 to −1.9; P=0.003).”

Kalil AC, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
December 11, 2020. DOI: 10.1056/NEJMoa2031994

Tocilizumab.
Evidencia aportada por estudios RECOVERY y REMAP-CAP apoyan uso de Tocilizumab en un
subgrupo definido de pacientes.

Estudio RECOVERY:
Recovery es un proyecto de investigación en tratamientos para la COVID-19 que conduce varios experimentos clínicos aleatorizados,
de etiqueta abierta y adaptativos. Incluye pacientes hospitalizados (131 sitios en el Servicio Nacional de Salud en el Reino Unido) con
sospecha clínica o infección por SARS-CoV-2 confirmada. Ha reclutado más de 38 mil participantes desde el 19 de marzo de 2020.
Hasta 21 días después de ingresar al proyecto, un subgrupo de 4 116 pacientes con evidencia clínica de la COVID-19 progresivo
(saturación de oxígeno <92% al ambiente o recibiendo oxigenoterapia y proteína C reactiva ≥75 mg/L) fueron aleatorizados a recibir
tocilizumab adicional al tratamiento estándar (n=2 022) o solo tratamiento estándar (n=2 094).

La edad promedio de los participantes fue de 63.6 (DE 13.7) años y al igual que las otras características demográficas registradas
fueron comparables entre los grupos. Al momento de la aleatorización 562 (14%) pacientes recibían ventilación mecánica invasiva,
1686 (41%) soporte ventilatorio no invasivo y 1868 (45%) oxigeno suplementario. La mediana de proteína C reactiva fue 143 mg/L
(RIQ 107-204) y 3 375 (82%) de los pacientes habían recibido corticoesteroides al momento de la aleatorización.

Los principales hallazgos con el uso de tocilizumab fueron:

- Los pacientes asignados a tocilizumab presentaron una menor mortalidad a 28 días comparados con los de tratamiento
estándar (29% vs 33%; RR 0.86, IC95% 0.77-0.96). Este efecto fue independiente del momento de inicio de la terapia y
similar en todos los subgrupos preespecificados, incluido el nivel de soporte ventilatorio en el momento de la
aleatorización.
- En un análisis exploratorio incluyendo solo pacientes con prueba positiva para SARS-CoV-2 (n=3 858), el resultado sobre
mortalidad fue similar (RR 0.87, IC95% 0.78-0.98).
- Los pacientes asignados a tocilizumab tuvieron tasa de supervivencia a 28 días en comparación con el tratamiento
estándar (54% vs 47%; RR 1.22, IC95% 1.12-1.34).
- El uso de tocilizumab se asoció con una reducción del riesgo del desenlace compuesto de inicio de ventilación mecánica
invasiva o muerte (33% vs 38%; RR 0.85, IC95% 0.78-0.93).
- La asignación al grupo de tocilizumab redujo el uso de hemodiálisis o hemofiltración (5%, vs 7%; RR 0.75, IC95% 0.59-
0.96).
- El uso de tocilizumab no tuvo ningún efecto significativo en:
<Requerimiento de soporte ventilatorio (no invasivo o ventilación mecánica invasiva), entre los pacientes que no tenían soporte
ventilatorio en el momento de la aleatorización.
<En contraste, en los pacientes con ventilación mecánica invasiva en el momento de la aleatorización, no tuvo efecto en la tasa de
extubación exitosa.
No se identificó un exceso de muertes por otras infecciones ni diferencias en la frecuencia de arritmias cardiacas mayores.
Solo se reportaron tres eventos adversos serios en pacientes asignados a tocilizumab: una otitis externa, una bacteremia por
Staphylococcus aureus y un absceso pulmonar. Todos se resolvieron con el tratamiento estándar.
El uso de dexametasona se asoció con una reducción en mortalidad por todas las causas a 28 días.

https://cardioinfantil.org/recados-unidad-sintesis-transferencia/tocilizumab-y-covid-19/

Estudio REMAP-CAP:

Tocilizumab redujo la mortalidad del 35,8 por ciento al 27,3 por ciento en comparación con la atención estándar: una reducción
absoluta del 8,5 porciento y una reducción relativa de mortalidad del 24 porciento.
IDSA Guidelines on the Treatment and Management of Patients with COVID-19.
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
“DESIGN: Observational multicenter cohort study. SETTING: A total of 23 acute care hospitals in
four states. PATIENTS: One-hundred eighteen patients admitted between March 13, 2020, and
April 16, 2020. Eighty-one patients received tocilizumab, and 37 were untreated and served as a
control group. MEASUREMENTS AND MAIN RESULTS: The main outcome was mortality and was
analyzed by timing of tocilizumab dosing. Early dosing was defined as a tocilizumab dose
administered prior to or within 1 day of intubation. Late dosing was defined as a dose
administered greater than 1 day after intubation. A control group that was treated only with
standard of care, and without tocilizumab, was used for comparison. Early tocilizumab therapy
was associated with a statistically significant decrease in mortality as compared to patients
who were untreated (p = 0.003). Dosing tocilizumab late was associated with an increased
mortality compared with the untreated group (p = 0.006). CONCLUSIONS: Early tocilizumab
administration was associated with decreased mortality in critically ill severe acute respiratory
syndrome coronavirus-2 patients, but a potential detriment was suggested by dosing later in a
patient’s course.”

Petrak, RM, et al. Early Tocilizumab Dosing Is Associated With Improved Survival in Critically Ill Patients Infected With Severe Acute
Respiratory Syndrome Coronavirus-2, Critical Care Explorations: April 2021 - Volume 3 - Issue 4 - p e0395
doi: 10.1097/CCE.0000000000000395

CÓDIGO ATC L04AC07

Financiado con recursos de la UPC para uso en artritis reumatoide refractaria a tratamiento con fármacos anti-
reumáticos modificadores de la enfermedad (FARME) no biológicos. En otros usos no Financiados según indicaciones
autorizadas se prescribe vía: MIPRES - Codigo CUPS 08394; 5064 [TOCILIZUMAB] 20mg/1ml.

Medicamento regulado, circular numero 10 de 2020, precio de venta máximo de los proveedores $825.859 y precio
de venta máximo al paciente $ 883.667 (200 mg).
https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/MET/circular-10-de-
2020.pdf

No aprobación INVIMA para su uso en pacientes con COVID-19:

https://www.invima.gov.co/documents/20143/1266661/
Acta+No+53+de+2013+SEMPB+final.pdf/96c2b56a-44c9-ec79-8303-60f0de9bc459?
t=1561674575621

http://web.sivicos.gov.co/registros/pdf/1355835_2015040356.pdf

https://pospopuli.minsalud.gov.co/PospopuliWeb/paginas/resultadomedicamentos.aspx?
value=H4sIAAAAAAAEAGNgZGBg
%2bA8EIBoE2EAM2eT8lMz0fFsjQwtztaTS4sLS1JRE25L85MyczKpSbgAxxsvFNQAAAA%3d%3d

Sentencias Corte Suprema de Justicia Colombia para Medicamentos no

soportados por INVIMA:
Sentencia T-1214 de 2008: “… el alcance del registro del INVIMA no puede
interpretarse como un criterio excluyente sobre la idoneidad de los
medicamentos.
Sentencia T- 425 de 2013: “En principio, debe prevalecer el criterio del médico
tratante respecto de la idoneidad del tratamiento médico que se le debe prestar
a las personas, porque este es el profesional que cuenta con los conocimientos
médico científicos...

Tomado de: https://twitter.com/dkastresana

Para definir uso de Tocilizumab en pacientes con COVID-19 se recomienda discusión del caso
por parte de una Junta multidisciplinaria con al menos participación de 3 especialidades
(hematología, infectología, medicina interna, pediatría, neumología, cuidado intensivo,
reumatología, urgenciología, inmunología clínica).

Consenso colombiano de atención, diagnóstico y manejo de la infección por

SARS-COV-2/COVID-19 en establecimientos de atención de la salud Recomendaciones basadas
en consenso de expertos e informadas en la evidencia ACIN-IETS. ADENDO: ACTUALIZACIÓN
CONSENSO 27/06/2020. Tocilizumab, pagina 5.

http://revistainfectio.org/index.php/infectio/article/view/895/982
Indicaciones:
Pacientes COVID-19 hospitalizados:
A. Sala general, con deterioro respiratorio progresivo.
B. UCI, dentro de las primeras 24 horas de ingreso a UCI por deterioro respiratorio.
y
Tiempo de evolución entre 7-21 dias.
Hipoxia: Saturación de Oxigeno < 92% (FiO2 21%).
Inflamación sistémica:
PCR ≥75 mg/L, punto de corte ideal seria 100 mg/L.
o
PCR > 50 mg/L, si su valor se duplicó en las últimas 24 a 48 h.
o
IL 6 > 40 pg/mL, requiere MIPRES, INTERLEUQUINA 6 CÓDIGO CUPS 906853.

Niveles elevados de IL 6 se asocian a LDH > 250 UI/ml, recuento absoluto de linfocitos < 600
células/mm3 y niveles de Dímero D mayores a 1500 ng/ml.

Contraindicaciones:
- Recuento absoluto de neutrófilos menor a 500 células/ uL.
- Recuento plaquetario menor a 50000 células/ uL.
- Transaminasas ALT/AST elevadas más de 5 veces con respecto al límite superior del
valor de referencia (hombres 29-33 U/L, mujeres 19-25 U/L).
- Diverticulitis activa.
- Enfermedad inflamatoria intestinal u otra condición que predisponga a perforación
intestinal.
- Tuberculosis activa.
- Sobreinfección bacteriana o fúngica activa.
- Historia de reacciones alérgicas severas con los anticuerpos monoclonales.
- Embarazo.

Precauciones:
- Monitorizar ALT/AST, Hemograma, PCR, LDH, Dímero D y Ferritina de forma diaria
durante 5 días.
- El riesgo de sobreinfecciones en pacientes con VMI se aumenta 2 a 3 veces con el uso
de Tocilizumab (54% vs. 26%; p<0.001) - medRxiv 2020.05.29.20117358.
 - Se debe vigilar progresión a sHLH – Linfohistiocitosis hemofagocitica secundaria
(presentación severa del síndrome de liberación de citoquinas: pancitopenia,
hipertrigliceridemia, hiperferritinemia, aumento de LDH e hipofibrinogenemia) - CHEST
2020; 158(1): e15-e19.

Dosis:
- Dosis basada en el peso del paciente:
>90 kg: 800 mg.
>65 - ≤90 kg: 600 mg.
>40 kg - ≤65 kg: 400 mg.
≤40 kg: 8 mg/kg.
- Diluir en 100 a 150 ml de SSN y pasar en perfusión de 60 a 90 minutos.
- Segunda dosis a las 12 a 24 horas según evolución (Recovery 29% de los pacientes
requirieron 2 dosis).
- No se requiere ajuste de la dosis en pacientes con disminución de la Tasa de Filtración
Glomerular.
- En pacientes con Hemodiálisis realizar la sesión correspondiente al menos 4 horas antes
de la administración de Tocilizumab.
- Se debe continuar con la administración de Dexametasona IV.
- Presentación comercial: viales 80, 200, y 400 mg (20 mg/ml).

Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19
Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in
the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen
therapy) and evidence of systemic inflammation (C-reactive protein [CRP] ≥75 mg/L) were eligible for
randomisation to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of
400 mg to 800 mg (depending on weight) given intravenously. A second dose could be given 12 to 24
hours later if the patient’s condition had not improved. The primary outcome was 28-day mortality,
assessed in the intention-to-treat population.
Findings Between 23 April 2020 and 24 January 2021, 4116 adults were included in the assessment of
tocilizumab, including 562 (14%) patients receiving invasive mechanical ventilation, 1686 (41%) receiving
non-invasive respiratory support, and 1868 (45%) receiving no respiratory support other than oxygen.
Median CRP was 143 [IQR 107-204] mg/L and 3385 (82%) patients were receiving systemic corticosteroids
at randomisation. Overall, 596 (29%) of the 2022 patients allocated tocilizumab and 694 (33%) of the
2094 patients allocated to usual care died within 28 days (rate ratio 0·86; 95% confidence interval [CI]
0·77-0·96; p=0·007). Consistent results were seen in all pre-specified subgroups of patients. In particular,
a clear mortality benefit was seen in those receiving systemic corticosteroids. Patients allocated to
tocilizumab were more likely to be discharged from hospital alive within 28 days (54% vs. 47%; rate ratio
1·22; 95% CI 1·12-1·34; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline,
patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical
ventilation or death (33% vs. 38%; risk ratio 0·85; 95% CI 0·78-0·93; p=0·0005).

In terms of outcomes, patients randomized to Tocilizumab had clinically meaningful Δ:

-decreased 28 day mortality (29 vs 33%; NNT 25)
-lower likelihood of requiring IMV (12 vs 15%; NNT 33)
-lower likelihood of requiring RRT (5 vs 7%; NNT 50)
-shorter hospital LOS (median 20 vs 28 days)
The RECOVERY trial contains over three times as many deaths as all the previous trials
combined. When all 8 trials are considered together, allocation to Tocilizumab is associated with
a 13% proportional reduction in 28-day mortality (death rate ratio 0·87, 95% CI 0·79-0·96,
p=0·005
https://threadreaderapp.com/thread/1360057691700424707.html?s=09

CRP was chosen as the biomarker for inflammation in this study since it is widely used and
affordable worldwide, it is correlated with serum IL-6 levels, and early clinical studies of COVID-
19 had reported it to be associated with severity and prognosis, with a value of >50 mg/L
associated with severe disease and a level of around 75 mg/L distinguishing fatal from non-fatal
cases.

One concern is that Tocilizumab can cause arrythmias & increase the risk of secondary infections.
Notably there was no increase in cardiac arrythmias, unexplained mortality, or infection related mortality.
This suggests that a single dose of Tocilizumab does not have major side effects.

Patients enrolled in the main RECOVERY trial and with clinical evidence of a hyperinflammatory
state may be considered for a second randomisation if they meet the following criteria:
• Randomised into the main RECOVERY trial no more than 21 days ago
• Clinical evidence of progressive COVID-19:
- Oxygen saturation <92% on room air or requiring oxygen (or in children, significant systemic
disease with persistent pyrexia, with or without evidence of respiratory involvement); and
- C-reactive protein (CRP) ≥75 mg/L.
• No medical history that might, in the opinion of the attending clinician, put the patient at
significant risk if they were to participate in this aspect of the RECOVERY trial
Contraindications and cautions Tocilizumab
- Known hypersensitivity to tocilizumab.
- Evidence of active TB infection.
- Clear evidence of active bacterial, fungal, viral, or other infection (besides COVID19).
Dose of Tocilizumab was determined by body weight (800 mg if weight >90kg; 600 mg if weight
>65 and ≤90 kg; 400 mg if weight >40 and ≤65 kg; and 8mg/kg if weight ≤40 kg). A second dose
could be given 12 to 24 hours later if, in the opinion of the attending clinician (29% received 2
doses in Tocilizumab arm).
Tocilizumab by intravenous infusion
Tocilizumab should be given as a single intravenous infusion over 60 minutes in 100 ml sodium
chloride 0.9%. A second dose may be given ≥12 and <24 hours later if, in the opinion of the
attending clinician, the patient’s condition has not improved.

COVINTOC trial.

“Among the subset of patients who had severe COVID-19 at baseline, the proportions of
patients who had disease progression (ie, died) up to day 28 were 16% (eight of 50) in the
tocilizumab group and 34% (14 of 41) in the standard care group, with a difference of –18·15 (–
37·79 to 2·43; p=0·044”

“180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab
group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group
inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses.
One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not
receive any study medication and was not included in the modified intention-to-treat population but was still
included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group
completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients
in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference –3·71 [95% CI –18·23
to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard
care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event
was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were
reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were
no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and
15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study.”
Tocilizumab plus standard care versus standard care in patients in India with moderate to
severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label,
multicentre, randomised, controlled, phase 3 trial.
Lancet Respir Med 2021. Published Online March 4, 2021. https://doi.org/10.1016/
S2213-2600(21)00081-3

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00081-3/fulltext

Roche actualiza los datos sobre el ensayo clínico fase III REMDACTA con Actemra/RoActemra
más Veklury, en pacientes con neumonía grave asociada a COVID-19 / 11.03.2021

https://www.roche.es/es_es/comunicacion/actualidad/2021/Marzo/Roche-REMDACTA-
Actemra-RoActemra-Veklury-COVID-19.html

IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Published by
IDSA on 4/11/2020. Last updated, 2/22/2021.
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-
management/?s=09

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a

randomised, controlled, open-label, platform trial. RECOVERY Collaborative Group. Posted
February 11, 2021. https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1?s=09

Tocilizumab reduces deaths in patients hospitalised with COVID-19.

https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-
covid-19?s=09

RANDOMISED EVALUATION OF COVID-19 THERAPY (RECOVERY).

https://www.recoverytrial.net/files/recovery-protocol-v13-0-2021-01-26.pdf

Statistical Analysis Plan - Version 2.0 - Date: 04 November 2020

Aligned with protocol version: 10.1, 01 November 2020
https://www.recoverytrial.net/files/recovery-sap-v2-0_2020-11-04.pdf/

Veiga VC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or
critical coronavirus disease 2019: randomised controlled trial BMJ 2021; 372 doi:
https://doi.org/10.1136/bmj.n84 (Published 20 January 2021).

Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised
patients with severe COVID-19 associated pneumonia.

https://www.roche.com/investors/updates/inv-update-2020-07-29.htm

Stone JH, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. Published on
October 21, 2020, at NEJM.org. DOI: 10.1056/NEJMoa2028836

Zhang Chi, et al. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor
antagonist tocilizumab may be the key to reduce mortality. International Journal of
Antimicrobial Agents 55 (2020) 105954. https://doi.org/10.1016/j.ijantimicag.2020.105954

https://www.sciencedirect.com/science/article/pii/S0924857920301047

Sciascia S, et al. Pilot prospective open, single-arm multicentre study on off-label use of
tocilizumab in severe patients with COVID-19. Clinical and Experimental Rheumatology 2020;
38: 529-532.

https://www.clinexprheumatol.org/abstract.asp?a=15723

Fu, B., et al. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med
18, 164 (2020). https://doi.org/10.1186/s12967-020-02339-3

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02339-3

Guaraldi G, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study.
Lancet Rheumatol 2020, Published Online June 24, 2020. https://doi.org/10.1016/S2665-
9913(20)30173-9

https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30173-9/fulltext

Xiaoling Xu, et al. Proceedings of the National Academy of Sciences May 2020, 117 (20) 10970-
10975; doi: 10.1073/pnas.2005615117

https://www.pnas.org/content/117/20/10970.short

Luo, P, et al. Tocilizumab treatment in COVID‐19: A single center experience. J Med Virol. 2020;
92: 814– 818. https://doi.org/10.1002/jmv.25801

https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25801

Alzghari SK, et al. Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review. J
Clin Virol. 2020 Jun; 127: 104380. Published online 2020 Apr 21.
doi: 10.1016/j.jcv.2020.104380

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194791/

Cala-García JD, et al. Recovery of COVID-19 acute respiratory distress syndrome with
tocilizumab: successful outcome in two critically ill patients. Future Medicine, Published
Online:14 Jul 2020. https://doi.org/10.2217/imt-2020-0154

https://www.futuremedicine.com/doi/10.2217/imt-2020-0154#.XxQ-XMdmTfo.twitter

Iwamoto, M, et al. Effective and safe administration of tocilizumab to a patient with rheumatoid
arthritis on haemodialysis. Rheumatol Int 31, 559–560 (2011). https://doi.org/10.1007/s00296-
010-1430-5
https://link.springer.com/article/10.1007/s00296-010-1430-5#citeas

Fontana F, et al. COVID-19 pneumonia in a kidney transplant recipient successfully treated with
tocilizumab and hydroxychloroquine. Am J Transplant. 2020; 20:1902–1906.
https://doi.org/10.1111/ajt.15935

https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.15935

Morrison AR, et al. Acute hypertriglyceridemia in patients with COVID‐19 receiving tocilizumab.
J Med Virol. 2020;1–2. https://doi.org/10.1002/jmv.25907

https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25907

De Luna G, et al. Rapid and severe Covid-19 pneumonia with severe acute chest syndrome in a
sickle cell patient successfully treated with tocilizumab. Am J Hematol. 2020; 95:876–878.
https://doi.org/10.1002/ajh.25833

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ajh.25833

Mihai C, et al. COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD.
Annals of the Rheumatic Diseases 2020; 79: 668-669. http://dx.doi.org/10.1136/annrheumdis-
2020-217442

https://ard.bmj.com/content/79/5/668.abstract

Zhang X, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated
with tocilizumab. Blood Adv. 2020 Apr 14; 4(7): 1307–1310. Published online 2020 Apr 3. doi:
10.1182/bloodadvances.2020001907

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160284/

Cellina M, et al. Favorable changes of CT findings in a patient with COVID-19 pneumonia after
treatment with tocilizumab. Diagn Interv Imaging. 2020;101(5): 323-324.
doi: 10.1016/j.diii.2020.03.010

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270926/
Michot JM, et al. Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related
respiratory failure: a case report. Annals of Oncology (2020).
doi: https://doi.org/10.1016/j.annonc.2020.03.300.

https://www.annalsofoncology.org/article/S0923-7534(20)36387-0/pdf

Somers EC, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19.
medRxiv 2020.05.29.20117358; doi: https://doi.org/10.1101/2020.05.29.20117358

https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1

Radbel J, et al. Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A

Cautionary Case Report. CHEST 2020; 158(1): e15-e19.
https://doi.org/10.1016/j.chest.2020.04.024

https://www.sciencedirect.com/science/article/abs/pii/S0012369220307649

Sarilumab.
Evidencia actual no apoya uso de Sarilumab.

Lescure FX, et al. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a
randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2021 Published
Online March 4, 2021. https://doi.org/10.1016/ S2213-2600(21)00099-0

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00099-0/fulltext

Sanofi and Regeneron provide update on Kevzara® (sarilumab) Phase 3 U.S. trial in COVID-19
patients.
https://www.sanofi.com/-/media/Project/One-Sanofi-Web/Websites/Global/Sanofi-COM/
Home/media-room/press-releases/2020/2020-07-02-22-30-00-2057183-en.pdf

What is the role of the IL-6 inhibitor sarilumab (Kevzara) in the treatment of coronavirus disease
2019 (COVID-19)?
https://www.medscape.com/answers/2500114-197456/what-is-the-role-of-the-il-6-inhibitor-
sarilumab-kevzara-in-the-treatment-of-coronavirus-disease-2019-covid-19

Anticuerpos Monoclonales

No disponibles en Colombia.

Monoclonal Antibodies.
https://www.idsociety.org/covid-19-real-time-learning-network/therapeutics-and-
interventions/monoclonal-antibodies/?s=09

Guidelines
Among ambulatory care patients, IDSA guidelines suggest the use of bamlanivimab/etesivimab
in patients with mild to moderate COVID-19 who are at high risk for progression to severe
disease.

The guidelines note that for patients at high risk for progression to severe disease, the data are
strongest for bamlanivimab/etesevimab. Bamlanivimab monotherapy or casirivimab/imdevimab
may have similar clinical benefit, but data are more limited.
The FDA EUA defines high risk patients as meeting at least one of the following criteria: 
Have a body mass index ≥35; 
Have chronic kidney disease; 
Have diabetes; 
Have immunosuppressive disease; 
Are currently receiving immunosuppressive treatment; 
Are ≥65 years of age; 
Are ≥55 years of age AND have cardiovascular disease, OR hypertension, OR chronic obstructive
pulmonary disease/other chronic respiratory disease; 
Are 12 – 17 years of age AND have BMI ≥85th percentile for their age and gender based on CDC
growth charts, OR sickle cell disease, OR congenital or acquired heart disease, OR
neurodevelopmental disorders, for example, cerebral palsy, OR a medical-related technological
dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not
related to COVID-19), OR asthma, reactive airway or other chronic respiratory disease that
requires daily medication for control.   
Among hospitalized patients with severe COVID-19, IDSA recommends against bamlanivimab
monotherapy.

NIH guidelines recommend the use of bamlanivimab 700 mg plus etesevimab 1,400 mg for
outpatients with mild to moderate COVID-19 who are at high risk of clinical progression.

NIH recommends against the use of bamlanivimab 700 mg plus etesevimab 1,400 mg for
patients who are hospitalized because of COVID-19, except in a clinical trial. However, they
state the combination should be considered for persons with mild to moderate COVID-19 who
are hospitalized for a reason other than COVID-19 but who otherwise meet the EUA criteria.

Lilly's bamlanivimab (LY-CoV555) administered with etesevimab (LY-CoV016) receives FDA

emergency use authorization for COVID-19
February 9, 2021
Monoclonal antibodies that bind to overlapping epitopes of the SARS-CoV-2 spike protein. These
antibodies target the receptor binding domain of the viral spike protein, potentially blocking viral cell
entry.
- Bamlanivimab and etesevimab administered together authorized for treatment of recently diagnosed,
mild to moderate COVID-19 in patients who are high risk for progression to severe COVID-19
- FDA authorizes shortened infusion time for both of Lilly's neutralizing antibody therapies authorized for emergency use
INDIANAPOLIS, Feb. 9, 2021 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization
(EUA) for investigational bamlanivimab (LY-CoV555) 700 mg and etesevimab (LY-CoV016) 1400 mg together, Eli Lilly and Company
(NYSE: LLY) announced today. This therapy is authorized for the treatment of mild to moderate COVID-19 in patients aged 12 and
older who are at high risk for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab and etesevimab should be
administered together via a single intravenous infusion as soon as possible after a positive COVID-19 test and within 10 days of
symptom onset.

In addition, the FDA has authorized infusion times for bamlanivimab alone and bamlanivimab and etesevimab together to be as
short as 16 or 21 minutes, respectively – a significant reduction from the previously authorized time of 60 minutes. This decision has
been made in response to feedback received from front-line nurses and doctors administering these infusions and are aimed at
reducing the burden on the healthcare system.

The EUA is based on Phase 3 data from the BLAZE-1 trial, announced January 26, 2021, which demonstrated bamlanivimab and
etesevimab together reduced the risk of COVID-19 hospitalizations and death by 70 percent. These data replicate earlier results,
published in The Journal of the American Medical Association, in a much larger group of patients. Additionally, the outcomes seen
with bamlanivimab and etesevimab together are consistent with the reduction in risk of hospitalization or ER visits seen with
bamlanivimab alone. The most common adverse event more often reported for patients receiving bamlanivimab and etesevimab
together versus placebo was nausea on the day of infusion.

While Phase 2 and Phase 3 trials evaluated a range of doses of bamlanivimab alone and bamlanivimab and etesevimab together,
data demonstrated consistent and similar clinical effects among all doses studied. Additionally, initial results from an ongoing Phase
2 study provide viral load and pharmacodynamic/pharmacokinetic data which demonstrated bamlanivimab 700 mg and etesevimab
1400 mg together produced similar effects to those observed in the Phase 3 trial with bamlanivimab 2800 mg and etesevimab 2800
mg together. Together, these data provide confidence in the authorized dose, which expands available supply to help more patients
without sacrificing potential efficacy.

No disponible en Colombia.
https://investor.lilly.com/news-releases/news-release-details/lillys-bamlanivimab-ly-cov555-
administered-etesevimab-ly-cov016?s=09

Colchicina.
Evidencia actual no apoya uso de Colchicina en pacientes con COVID-19:

RECOVERY trial closes recruitment to colchicine treatment for patients hospitalised with COVID-
19. 5 March 2021.

https://www.recoverytrial.net/news/recovery-trial-closes-recruitment-to-colchicine-treatment-
for-patients-hospitalised-with-covid-19

ColCorona. PREGUNTAS FRECUENTES. https://es.colcorona.net/faq?s=09

Randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by

polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned
to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30
days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.

Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the
patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79;
95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-
confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the
colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In
these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99)
for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and
0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in
the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients
(P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups
(P<0.0001).

Tardif JC, et al. Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19. medRxiv
2021.01.26.21250494; doi: https://doi.org/10.1101/2021.01.26.21250494

“Colchicine interrupts microtubule assembly which is required for cellular processes such as maintenance of cell
shape, intracellular trafficking, cell signaling, migration and division. Its anti-inflammatory effects are primarily due to
inhibiting neutrophil recruitment, chemotaxis, adhesion, mobilization, superoxide production and inflammasome
activation. Colchicine has also exhibited anti-viral properties in vitro through interruption of the tubular network
required by some viruses for replication.

Some viruses require the microtubule network for their replication cycle including viral entry, intracellular transport,
virion assembly and exit. Colchicine has been shown to interrupt hepatitis C, flaviviruses and varicella-zoster
replication in vitro and respiratory syncytial virus (RSV) replication in mice. However, other viruses such as herpes
simplex (HSV) do not depend on the cytoskeleton for replication and are potentially unaffected by colchicine.

Pre-clinical studies have suggested that colchicine treatment can in fact decrease macrophage infiltration and lead to
increased viral load in both the heart and pancreas of coxsackievirus B3 infected mice leading to increased mortality.”

McEwan T, Robinson PC. A systematic review of the infectious complications of colchicine and
the use of colchicine to treat infections. Semin Arthritis Rheum. 2020 Dec 17;51(1):101-112.
doi: 10.1016/j.semarthrit.2020.11.007

Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of Colchicine vs Standard Care on
Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With
Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open.
2020;3(6): e2013136. doi:10.1001/jamanetworkopen.2020.13136

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593

COVID and Colchicine. 16 Feb 2021

https://foamcast.org/2021/02/16/covid-and-colchicine/

N-Acetilcisteína.
Evidencia actual no apoya uso de N-Acetilcisteína en pacientes con COVID-19:

A Study of N-acetylcysteine in Patients with COVID19 Infection. https://www.cancer.gov/about-

cancer/treatment/clinical-trials/search/v?id=NCI-2020-03373

Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease.

https://clinicaltrials.gov/ct2/show/NCT04419025
Inpatients:
N-acetylcystine (NAC) 25 mg/kg PO (rounded up to the nearest 600 mg) q4hrs until discharge
N-acetylcysteine (NAC) 1200 mg PO BID x 1 week post-discharge
Outpatients:
- N-acetylcysteine (NAC) 2400 mg PO x 1 then 1200 mg PO BID x 2 weeks

N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19

April 14, 2020. https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-
evidence-for-effectiveness-in-treating-covid-19/

Pan Luo, et al. Perspectives for the Use of N-acetylcysteine as a Candidate Drug to Treat COVID-
19, Mini-Reviews in Medicinal Chemistry (2021) 21: 268.
https://doi.org/10.2174/1389557520666201027160833

Puyo C, et al. Case Report: Use of hydroxychloroquine and N-acetylcysteine for treatment
of a COVID-19 patient [version 2; peer review: 2 not approved] F1000Research 2020, 9:491
https://doi.org/10.12688/f1000research.23995.2

Methods. This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency
Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory
failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an
oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21
g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation.
Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and
mortality.
Results. Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex,
comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest
computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation
and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was
observed in secondary endpoints.
Conclusions. Administration of NAC in high doses did not affect the evolution of severe COVID-19.

Garcia de Alencar JC, et al. COVID Register Group, Double-blind, Randomized, Placebo-
controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome
Caused by Coronavirus Disease 2019 (COVID-19), Clinical Infectious Diseases, 2020;, ciaa1443,
https://doi.org/10.1093/cid/ciaa1443

De Flora S, et al. Rationale for the use of N‐acetylcysteine in both prevention and adjuvant
therapy of COVID‐19. The FASEB Journal. 2020; 34: 13185–13193. First published: 11 August
2020. https://doi.org/10.1096/fj.202001807

Vial 300 mg/ 3 ml, diluir en 50 a 100 ml de SSN o DAD 5% y pasar en perfusión de 15 a 30
minutos.
Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk
Manag. 2020; 16: 1047-1055. Published 2020 Nov 2. doi:10.2147/TCRM.S273700
PROFILAXIS TROMBOEMBOLICA
ENOXAPARINA – HEPARINA SC.
La tromboprofilaxis solo esta recomendada en pacientes que requieran hospitalización por
COVID-19.
No se recomienda la indicación generalizada de anticoagulación plena teniendo en cuenta
reportes de estudios observacionales con aumento de la mortalidad:

“When comparing treatments through multivariable analysis, risk of inhospital mortality was 2.3 times greater in
patients receiving preemptive therapeutic anticoagulation (95% CI = 1.0–4.9; p = 0.04). Additionally, the average
treatment effects were higher (β = 0.11, p = 0.01) in the therapeutic group.”

Motta, JK, et al. Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in Coronavirus Disease 2019,
Critical Care Explorations: December 2020 - Volume 2 - Issue 12 - p e0309. doi: 10.1097/CCE.0000000000000309

Evidencia actual no apoya el uso adicional de antiagregación plaquetaria con Acido Acetil Salicilico.
Se han descrito múltiples eventos trombóticos que incluyen el sistema venoso y arterial:
trombosis venosa profunda (TVP), embolia pulmonar (EP), infarto de miocardio, isquemia
mesentérica, isquemia de miembros inferiores, y accidente cerebro vascular.
A pesar de la tromboprofilaxis, la tasa de ETV (trombosis venosa profunda o embolia pulmonar)
en pacientes críticos reportada es de 5-10%. Bajo profilaxis la incidencia de ETV en pacientes
con COVID-19 no en área crítica varía entre 0.9% a 12.5% y en unidad de cuidados intensivos
(UCI) está entre el 16-35%. Por otro lado, se detectó mediante ultrasonido 25% de trombosis
asintomática, así como EP en ausencia de TVP. Considerando estos hallazgos, se ha insistido
que, ante el súbito deterioro clínico de un paciente, caracterizado por hipoxemia, la sospecha
de embolia pulmonar debe ser alta. Así como el empeoramiento de la relación ventilación
perfusión, la pérdida del reflejo vasoconstrictor por hipoxia que perpetúan el síndrome de
distrés respiratorio agudo (SDRA) deben orientarnos a marcada trombosis pulmonar
microvascular.

Revisión de la literatura:
“Cui et al reported that D-dimer levels also correlated with risk of venous thromboembolism: a level of
3.0 μg/mL had a sensitivity of 70.0%, specificity of 96.7%, and positive predictive value of 87.5%.
Maatman et al reported that standard prophylaxis against venous thromboembolism failed in 29 of 109
patients in the intensive care unit, and of those in whom it failed, all had D-dimer levels greater than 3.0
μg/mL.”
“Some evidence indicates that elevated D-dimer levels may predict higher risk of venous
thromboembolism despite standard prophylaxis. In a study of 240 critically ill patients with COVID-19,
Maatman et al reported a 28% rate of venous thromboembolism in patients receiving standard
prophylaxis. Elevated D-dimer (> 2.6 μg/mL) predicted venous thromboembolism with a sensitivity of
89.7%. The authors concluded that standard prophylactic anticoagulant doses may be insuffi cient to
prevent venous thromboembolism in high-risk patients.”
“Paranjpe et al, in an observational report of 2,773 patients with COVID-19 admitted to a single institution
in New York, found that those treated with full anticoagulation (786 patients, 28%) had a similar mortality
rate (22.5%) vs those treated with prophylaxis only (22.8%). But among mechanically ventilated patients,
in-hospital mortality was 29.1% for those treated with anticoagulation vs 62.7% for patients who did not
receive anticoagulation. Despite this dramatic reduction of mortality, the authors advise caution in
applying these findings, given the serious limitations of the report, ie, its observational nature and lack of
information on illness severity and indications for anticoagulation.”
“Piazza et al, thrombotic complications occurred in 2.6% of 229 non– critically ill hospitalized patients and
in 35.3% of 170 hospitalized critically ill patients.”
“Lodigiani et al, Among 388 patients hospitalizedwith COVID-19 (16% were critically ill), despite low-
molecular-weight heparin (LMWH) thromboprophylaxis in all patients in the intensive care unit and in
75% of those not in intensive care, symptomatic VTE occurred in 4.4% of patients, ischemic stroke in
2.5%, and MI in 1.1%”
“Zaid et al, A study of 115 patients with COVID-19 (71 with nonsevere and 44 with severe disease)
documented the presence of SARS-CoV-2 RNA in platelets and high platelet associated cytokine levels.”
“Nicolai et al, In vitro assays performed on peripheral blood samples in 3 patients with COVID-19
documented excessive platelet and neutrophil activation, assessed by degranulation and integrin IIb-IIIa
activation and immunofluorescence, compared with samples from 5 healthy control patients.”
“Roberts et al, The extent to which SARS-CoV-2 increases the risk of thromboembolism is unclear. AUK-
based study of 1877 hospital discharges related to COVID-19 and 18 159 related to non–COVID-19
medical illness did not differ in rates of hospital-associated VTE (4.8/1000 vs 3.1/1000; odds ratio, 1.6
[95% CI, 0.77-3.1]; P = .20). The high rate of VTE in COVID-19 may be less specific to the virus and
predominantly due to the overall illness severity and complications.”

DOSIS DE ENOXAPARINA SC

Dimero D Enoxaparina SC
< 3000 ng/ml Profilaxis estándar (0.5 mg/kg q 24 h)
40 mg día
Se debe continuar Enoxaparina SC hasta el egreso hospitalario.
≥ 3000 ng/ml Profilaxis alta intensidad (0.5 mg/kg q 12 h)
40 mg q 12 h
Fenotipo protrombotico en Se debe continuar Enoxaparina SC hasta el egreso hospitalario.
COVID-19. International Society on Thrombosis and Hemostasis
recomienda extender tromboprofilaxis hasta por 30 dias en
pacientes con alto riesgo de trombosis y bajo riesgo de
complicaciones hemorrágicas.
Evento trombotico Anticoagulación plena
confirmado 1 mg/kg q 12 h
Trombosis asociada a catéter: 6 semanas.
Tromboembolismo venoso:
12 semanas.
Sospecha de Anticoagulación plena
Tromboembolismo venoso 1 mg/kg q 12 h
Pacientes de alto riesgo Profilaxis alta intensidad (0.5 mg/kg q 12 h):
complicaciones por COVID-19 - Edad mayor de 65 años.
- COVID-19 critico.
- Cancer.
- Tromboembolismo venoso previo.
- Trombofilia.
- Inmovilización prolongada.
Se debe continuar Enoxaparina SC luego de egreso hospitalario según
evolución del caso.
 a IV heparin ACS nomogram: initial dose 60-U/kg bolus, then 12-18 U/kg/hour; target aPTT
49–67 seconds; target heparin anti-Xa 0.2–0.5 units/mL.
b AKI definition: doubling of creatinine in 48 hours or anuria.
Referencias bibliograficas:

Motta, JK, et al. Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in Coronavirus
Disease 2019, Critical Care Explorations: December 2020 - Volume 2 - Issue 12 - p e0309.
doi: 10.1097/CCE.0000000000000309

Piazza G, et al. Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19. JAMA.
Published online November 23, 2020. doi:10.1001/jama.2020.23422

Mucha SR, et al. Coagulopathy in COVID-19: Manifestations and management. Cleveland Clinic Journal of Medicine
August 2020, 87 (8) 461-468; DOI: https://doi.org/10.3949/ccjm.87a.ccc024
Morejon P. Coagulopatía y covid-19. http://www.siacardio.com/novedades/covid-19/coagulopatia-y-covid-19/

Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus
pneumonia. J Thromb Haemost 2020; 18(6):1421–1424. DOI: 10.1111/jth.14830
Maatman TK, et al. Routine venous thromboembolism prophylaxis may be inadequate in the hypercoagulable state of
severe coronavirus disease 2019. Crit Care Med 2020 May 27; 10.1097/CCM.0000000000004466.
DOI: 10.1097/CCM.0000000000004466

Paranjpe I, et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients
with COVID-19. J Am Coll Cardiol 2020 May 5; S0735-1097(20)35218-9. doi: 10.1016/j.jacc.2020.05.001

Paiter JH, et al. COVID-19 and Hypercoagulable State: A New Therapeutic Perspective. Arq. Bras. Cardiol. vol.114 no.5
São Paulo May 2020 Epub June 01, 2020. https://doi.org/10.36660/abc.20200308

Klok FA, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;
191:145–147. https://doi.org/10.1016/j.thromres.2020.04.013

Poissy J, et al. Pulmonary Embolism in Patients With COVID-19. Circulation. 2020; 142:184–6.
https://doi.org/10.1161/CIRCULATIONAHA.120.047430

Piazza G, et al. Registry of arterial and venous thromboembolic complications in patients with COVID-19. J Am Coll
Cardiol. 2020; 76(18):2060-2072. doi: 10.1016/j.jacc.2020.08.070

Zaid Y, et al. Platelets can associate with SARS-Cov-2 RNA and are hyperactivated in COVID-19. Circ Res. 2020.
doi: 10.1161/CIRCRESAHA.120.317703

Nicolai L, et al. Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and
coagulopathy. Circulation. 2020;142(12):1176- 1189. doi: 10.1161/CIRCULATIONAHA.120.048488

Lodigiani C, et al; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19
patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020; 191: 9-14.
doi: 10.1016/j.thromres.2020.04.024

Roberts LN, et al. Postdischarge venous thromboembolism following hospital admission with COVID-19. Blood. 2020;
136(11): 1347-1350. doi: 10.1182/blood.2020008086

Spyropoulos AC, et al; Subcommittee on Perioperative, Critical Care Thrombosis, Haemostasis of the Scientific,
Standardization Committee of the International Society on Thrombosis and Haemostasis. Scientific and
Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous
thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020; 18(8): 1859-1865.
doi: 10.1111/jth.14929

Moores LK, et al. Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST
Guideline and Expert Panel Report. Chest. 2020; 158: 1143-1163. doi: 10.1016/j.chest.2020.05.559

Wilner A. Anticoagulation for COVID-19: More Harm than Good? https://www.medscape.com/viewarticle/938013?

src=wnl_tp10n_201112_mscpedit&uac=251203AR&impID=2670371&faf=1&s=03

Multivitaminicos:
- Estudios clínicos no muestran beneficios con alta dosis de Zn y Acido ascórbico.

Thomas S, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on
Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The
COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2021; 4(2): e210369.
doi: 10.1001/jamanetworkopen.2021.0369

- Evidencia circunstancial asocia casos severos de COVID-19 con hipovitaminosis D.

Evidencia actual no apoya el uso sistematico de Vitamina D en pacientes con COVID-19:

“Study was undertaken as continuous prospective observational study of 6 weeks. Participants were
COVID-19 patients of age group 30–60 years admitted during the study period of 6 weeks. Study included
either asymptomatic COVID-19 patients (Group A) or severely ill patients requiring ICU admission (Group
B). Serum concentration of 25 (OH)D, were measured along with serum IL-6; TNFα and serum ferritin.
Standard statistical analysis was performed to analyze the differences. Current Study enrolled 154
patients, 91 in Group A and 63 patients in Group B. The mean level of vitamin D (in ng/mL) was 27.89 ±
6.21 in Group A and 14.35 ± 5.79 in Group B, the difference was highly significant. The prevalence of
vitamin D deficiency was 32.96% and 96.82% respectively in Group A and Group B. Out of total 154
patients, 90 patients were found to be deficient in vitamin D (Group A: 29; Group B: 61). Serum level of
inflammatory markers was found to be higher in vitamin D deficient COVID-19 patients viz. IL-6 level (in
pg/mL) 19.34 ± 6.17 vs 12.18 ± 4.29; Serum ferritin 319.17 ± 38.21 ng/mL vs 186.83 ± 20.18 ng/mL; TNFα
level (in pg/mL) 13.26 ± 5.64 vs 11.87 ± 3.15. The fatality rate was high in vitamin D deficient (21% vs
3.1%). Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in
vitamin D deficient COVID-19 patients”

Vitamin D is usually acknowledged for the maintenance of bone health and calcium–phosphorus metabolism, many
other roles like stimulation of insulin production, effects on myocardial contractility have been recently discovered.
Vitamin D plays an essential role in the immune system. Vitamin D interferes with the majority of the immune
systems cells such as macrophages, B and T lymphocytes, neutrophils and dendritic cells. The T and B lymphocytes
can form the active metabolite of vitamin D, 1,25(OH)2D3 which inhibits T cell proliferation and activation. Beside
this, vitamin D inhibits the production of pro-inflammatory cytokines and enhance the production of anti-
inflammatory cytokines.
Vitamin D inhibits the adaptive immune system and promotes the innate immune system which balances the
immune response and provides an overall anti-inflammatory response.

Jain A, et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its
correlation with inflammatory markers. Sci Rep 10, 20191 (2020). https://doi.org/10.1038/s41598-020-
77093-z

Meltzer DO, et al. Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-
19 Test Results. JAMA Netw Open. 2021;4(3): e214117. doi:10.1001/jamanetworkopen.2021.4117

Mansur JL, et al. “Vitamin D high doses supplementation could represent a promising alternative to
prevent or treat COVID-19 infection.” “El suplemento con altas dosis de vitaminaD podría representar una
alternativa promisoria para prevenir o tratar la infección por COVID-19.” Clinica e investigacion en
arteriosclerosis: publicacion oficial de la Sociedad Espanola de Arteriosclerosis vol. 32,6 (2020): 267-277.
doi: 10.1016/j.arteri.2020.05.003

“Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable—
links with ethnicity, obesity, age and institutionalization; latitude association; evidence from
experimental models of respiratory pathogens; preliminary reports of associations with COVID-19
severity in hospitalized patients; basic biology studies showing extensive vitamin D impacts on the
immune system underlying various anti-viral and anti-inflammatory responses; vitamin D responsive
genes altered in lung lymphocytes from COVID-19 patients.”

Griffin G, et al. Vitamin D and COVID-19: evidence and recommendations for supplementation. R. Soc.
open sci. 7: 201912. http://doi.org/10.1098/rsos.201912

Annweiler C, et al. COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older
patients (COVIT-TRIAL): study protocol for a randomized controlled trial. Trials 21, 1031 (2020).
https://doi.org/10.1186/s13063-020-04928-5

“Toxicity can include non-specific symptoms such as anorexia, weight loss, polyuria and heart
arrhythmias. The primary toxicity concern is elevated serum calcium concentration which can
lead to vascular and tissue calcification with subsequent damage to kidneys, blood vessels and
the heart. Risks are minimal, especially at recommended doses and most reports suggest a
toxicity threshold for vitamin D of 10,000 to 40,000 International Units per day (IU/d) and serum
concentrations of 200-240 ng/mL. for that severe toxicity to occur. Those doses and
concentrations are not recommended but highlight the fact that at more reasonable doses and
concentrations discussed below toxicity is not a big concern for most patients.
There are a limited number of foods that are sources of these compounds. Vitamin D-2 is found
mostly in mushrooms and fortified foods such as cereal. Vitamin D-3 is found primarily in
animal-based foods such as fish, liver, eggs and America's old favorite, cod-liver oil.”

Simonson W. Vitamin D dosing considerations in COVID-19. Geriatr Nurs. 2020; 41(5): 648-649.
doi: 10.1016/j.gerinurse.2020.08.011

Rastogi A, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a
randomised, placebo-controlled, study (SHADE study). Postgraduate Medical Journal Published
Online First: 12 November 2020. doi: 10.1136/postgradmedj-2020-139065

COVID-19 rapid guideline: vitamin D. NICE guideline. Published: 17 December 2020.

www.nice.org.uk/guidance/ng187

“There is an overlap between groups at risk of vitamin D deficiency and groups at high risk of
severe COVID-19, with a complex relationship of lower socioeconomic status and nutritional
status. Low vitamin D levels may be a marker of poor health so whether low vitamin D levels are
a cause of COVID-19 or a reflection of health status is a point of debate.
There is no high quality evidence that suggests taking vitamin D supplements is specifically
effective in the prevention or treatment of COVID-19.
For general health, it is important to have adequate vitamin D levels regardless of the effects on
COVID-19. The recommended daily intake for Canadians ranges from 400-800 IU (10-20 mcg)
daily depending on stage of life, with a tolerable upper intake level of 1,000-4,000 IU (25-100
mcg) daily.”

COVID-19 Scientific Advisory. Group Rapid Evidence Brief. January 7, 2021.

Vitamin D in the Treatment and Prevention of COVID-19.

https://www.albertahealthservices.ca/assets/info/ppih/if-ppih-covid-19-sag-rapid-review-
vitamin-d-treatment-and-prevention-covid-19.pdf
MEDICACION GENERAL.
- Dipirona 1 g IV cada 6 h o Acetaminofén 500 a 1000 mg VO cada 6 h en caso de dolor o
fiebre.
- Tramadol 50 mg IV cada 6 h en caso de dolor persistente.
- Metoclopramida 10 mg IV o VO cada 8 h en caso de nauseas o vómitos, previa
hidratación del paciente.
- Omeprazol 20 a 40 mg VO 30 minutos predesayuno (o 40 mg IV cada 24 h) o Famotidina
10 a 20 mg VO cada 12 horas o Sucralfate 1 g VO 3 veces al día, 1 h antes de los
alimentos, administrar antimicrobianos 2 h antes o 4 h después del Sucralfate para
disminuir riesgo de interacciones.
Indicar Famotidina o Inhibidores de bomba de protones en pacientes con factores de
riesgo para sangrado gastrointestinal: ventilación mecánica por ≥48 h, coagulopatía,
terapia de reemplazo renal, hepatopatía, y múltiples comorbilidades.

Famotidina en pacientes con Insuficiencia Renal:

Aclaramiento de creatinina > 10 ml/min: no se requieren ajustes en las dosis.
Creatinina ≤ 10 ml/min reducir las dosis en un 50% (o, alternativamente espaciar las
dosis al doble).
Famotidina no requiere MIPRES:
https://pospopuli.minsalud.gov.co/PospopuliWeb/paginas/resultadomedicamentos.aspx?
value=H4sIAAAAAAAEAGNgZGBg%2bA8EIBoE2EAM
%2beT8lMz0fFtjYzMztaTS4sLS1JRE27TE3PySzJTMvERuAByZdcw3AAAA
- Dihidrocodeina bitartrato jarabe 12,1 mg/ 5 ml a dosis de 5 ml VO cada 8 h o 7.5 ml VO
cada 12 h en caso de tos seca persistente, se deben vigilar interacciones
medicamentosas.
o
Acetaminofén/Codeína tabletas 325 mg/8-30 mg a dosis de 8-30 mg VO cada 6 a 8 h en
caso de tos seca persistente, se deben vigilar interacciones medicamentosas.

En caso no respuesta a codeína, se sugiere inicio Morfina, usar la mínima dosis

requerida para proveer alivio y titular de acuerdo a su necesidad. En caso de falla renal
o intolerancia se puede considerar el uso de Oxicodona o Hidromorfona IV/SC.

Dosis recomendadas de Morfina: Tos 1- 2 mg IV/SC cada 6 - 8 h - Disnea o dolor 2- 3 mg

IV/SC cada 6 h.
- Difenhidramina jarabe 12,5 mg/ 5 ml o Clorfeniramina jarabe 2 mg/ 5 ml a dosis de 10 a
20 ml vía oral en las noches en caso de insomnio persistente, se deben vigilar
interacciones medicamentosas.
- Bisacodilo 5 a 10 mg vía oral en las noches en caso de estreñimiento persistente.
- Loperamida 2 mg vía oral cada 8 h en caso de diarrea persistente, se deben vigilar
interacciones medicamentosas.
- Hidróxido de Aluminio suspensión a dosis de 30 ml vía oral en caso de síntomas
acidopépticos o tabletas 234 mg a dosis de 2 tabletas vía oral en caso de síntomas
acidopépticos.
- Salbutamol 100 ug/puff mas Bromuro de Ipratropium 20 ug/puff para utilizar con
inhalocamara en caso de broncoespasmo.
 No Micronebulizar por alto riesgo de generar aerosoles.
- Evitar AINES de forma sistémica en pacientes hospitalizados por COVID-19.
- Recomendaciones para el manejo del Delirium
• Para el manejo no farmacológico se recomienda identificar y tratar posibles causas,
incluyendo la oxigenoterapia para tratamiento de hipoxemia.
• En adultos:
► Delirium hiperactivo, se recomienda uso de Haloperidol vía IV/SC, usar la mínima
dosis requerida para proveer alivio y titular de acuerdo con su necesidad, considerar
uso por horario cada 8 horas si el síntoma es persistente.
► Delirium con predominio de insomnio por intranquilidad o agitación nocturna,
considerar uso de Quetiapina o Levomepromazina.

PARACLINICOS DE INGRESO / SEGUIMIENTO:

1. Gases arteriales con Lactato.
2. Hemograma.
3. BUN – Creatinina.
4. Ionograma (Sodio – Cloro – Potasio).
5. Calcio – Magnesio – Fosforo (opcional).
6. TGO – TGP – Bilirrubinas – Fosfatasa alcalina.
7. GGT (opcional).
8. Albumina – Globulinas – Proteínas totales (opcional).
9. Glicemia.
10. TP – TPT.
11. LDH.
12. Ferritina.
13. Dímero D.
14. Fibrinógeno (opcional).
15. IL-6 (opcional).
16. VSG.
17. PCR.
18. CPK total – MB.
19. Troponina I o T (opcional).
20. Péptidos natriuréticos BNP o NT-proBNP (opcional).
21. 25-hidroxicolecaliferol (25-OH-D3) (opcional).
22. Extendido de sangre periférica (opcional).
23. Procalcitonina sérica (opcional).
24. Presepsina (opcional).
25. Uroanálisis.
26. Microalbuminuria (opcional).
27. Electrocardiograma convencional.
28. Hemocultivos N.2, tomar al mismo tiempo en sitios de punción diferentes con agujas
diferentes.
29. Gram –cultivo aerobios – antibiograma en esputo (si paciente presenta tos con
expectoración).
Se recomienda no usar el uso del esputo inducido por el alto riesgo de formación de
aerosoles.
30. Baciloscopia seriada de esputo con cultivo para Micobacterias (si paciente presenta tos
con expectoración), (opcional).
 Se recomienda no usar el uso del esputo inducido por el alto riesgo de formación de
aerosoles.
31. Tamizar infecciones crónicas ocultas:
- VIH EIA o ELISA.
- VHB antígeno de superficie.
- VHB anticore total (opcional).
- VHC anticuerpos totales.
- VDRL sérico (opcional).
- Anticuerpos contra Treponema pallidum (opcional).
32. Antígeno Influenza (prueba rápida) en aspirado traqueal o hisopado nasofaríngeo o
Hipofaríngeo.
Muestra de aspirado traqueal debe ser tomada idealmente por Terapia Respiratoria.
33. Rt-PCR en aspirado traqueal para SARS-CoV-2. En caso de no posibilidad de aspirado
traqueal, tomar muestra de hisopado nasofaríngeo. Muestra de aspirado traqueal debe
ser tomada idealmente por Terapia Respiratoria.
Código CUPS 90.8.8.56 Identificación de otro virus (específica) por pruebas
moleculares rt-PCR.

No se requiere rt-PCR control.

Como alternativa al rt-PCR se podría utilizar la prueba inmunocromatográfica rápida

para la detección de antígeno SARS CoV 2 en-Hisopado nasofaríngeo e Hipofaríngeo (en
pacientes con síntomas de menos de 11 días de evolución).
CÓDIGO CUPS 906340 SARS CoV 2 [COVID-19] ANTÍGENO.

Se recomienda que las muestras clínicas tomadas para el diagnóstico de COVID-19 se conserven
a temperatura entre -2 a 8◦C, y luego de las 48 horas deben permanecer congeladas a una
temperatura de -70◦C.
El transporte de las muestras debe realizarse con geles o pilas congeladas, teniendo en cuenta
que temperaturas superiores a 8°C degradan la partícula viral.

En caso de muerte, se recomienda realizar la toma de muestra postmorten por hisopado

nasofaríngeo dentro de las primeras seis horas posteriores al fallecimiento.
Se debe también remitir entre 5 a 10 ml de sangre total en tubo con anticoagulante (EDTA/tapa
de color lila), obtenida mediante punción cardiaca con jeringa de 10 ml provista de aguja 18G o
20G, el tiempo de la toma de la muestra no debe ser mayor de 60 minutos postmorten. La
punción cardíaca se realiza en el sexto o séptimo espacio intercostal izquierdo, sobre la línea
mamaria o sobre la línea media entre la línea mamaria y la línea axilar anterior.

Orientaciones para el manejo, traslado y disposición final de cadáveres por SARS-CoV-2

(COVID-19) -Versión 05 / Código GIPG08. MINISTERIO DE SALUD Y PROTECCIÓN SOCIAL. Bogotá,
junio de 2020.
https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/ED/VSP/manejo-cadaveres-covid-19f.pdf

34. SARS-CoV-2 IgG – IgM (prueba rápida para detección de anticuerpos) si tiempo de
evolución es de 11 días o más con respecto al inicio de los síntomas.
La evidencia actual no recomienda realizar este tipo de estudios en pacientes con
tiempo de evolución con respecto al inicio de los síntomas menor a 11 días.
Código CUPS 90.6.2.70 SARS CoV 2 [COVID-19] ANTICUERPOS IgG.
 Código CUPS 90.6.2.71 SARS CoV 2 [COVID-19] ANTICUERPOS IgM.
35. Panel Respiratorio FILMARRAY™ o Anyplex™ II RV16 Detection en aspirado traqueal o
hisopado nasofaríngeo o hipofaríngeo (CODIGO CUPS 908859: IDENTIFICACION
SIMULTANEA DE MULTIPLES PATOGENOS POR PRUEBAS MOLECULARES), en pacientes
con neumonía grave, SDRA, sepsis o choque séptico para evaluar diagnóstico
diferencial de SARS- CoV-2/COVID-19 e identificar coinfecciones virales o bacterianas.
Muestra de aspirado traqueal debe ser tomada idealmente por Terapia Respiratoria.
Para información complementaria consultar en:
https://www.biomerieux.com.co/diagnostico-clinico/panel-respiratorio-filmarraytm
http://www.seegene.com/assays/anyplex2_rv16_detection

36.Mycoplasma pneumoniae IgM/IgG en suero (opcional).

37.Legionella pneumophila antígeno urinario (opcional).
38.Streptococcus pneumoniae antígeno urinario (opcional).
39.Radiografía de Tórax postero-anterior y lateral.
40.TAC de tórax simple en los siguientes escenarios:
- Pacientes con presentación severa de la enfermedad.
- Pacientes con sospecha de neumonía por COVID-19.
- Pacientes con radiografía de tórax normal o con alteraciones radiológicas inespecíficas a
quien se desea descartar un diagnóstico alterno.
- Pacientes con curso clínico no esperado, para detectar complicaciones y se considera
que debería implicar cambios en la conducta terapéutica.
41. Paraclínicos seriados:
- c/ 1 a 2 dias: Hemograma – BUN – Creatinina – Ionograma – PCR – LDH.
- c/ 2 a 3 dias: Dímero D (opcional)– Fibrinogeno (opcional) – Ferritina (opcional)– Procalcitonina
(opcional) – Presepsina (opcional).
- c/ 3 a 4 días: TGO – TGP – TP (opcional) – TPT (opcional).
- Electrocardiograma según evolución clínica del paciente.
- Gases arteriales con lactato control según evolución clínica del paciente.
- Radiografía de Tórax postero-anterior y lateral control según evolución clínica del paciente.
Recomendaciones en caso de pacientes que requieran TRAQUEOSTOMIA:

Se recomienda la realización de la traqueostomía cuando este indicada, en los pacientes COVID-19 sospechosos y confirmados
con pronóstico razonable de vida, después del 5 o 7 día de ventilación, previa valoración y consenso por el equipo quirúrgico y de
cuidado intensivo, asegurando que las condiciones clínicas, ventilatorias y hemodinámicas se encuentren controladas.

Se recomienda no esperar la negativización de la rt-PCR SARS-CoV-2 para realizar la traqueostomía en el paciente con diagnóstico de
COVID-19, ya que no se ha documentado excreción viral efectiva con cultivos positivos luego de la tercera semana de enfermedad.

Accini JL, et al. Actualización de la Declaración de consenso en medicina critica para la atención multidisciplinaria del paciente con
sospecha o confirmación diagnóstica de COVID-19 [Updated Consensus statement on critical medicine for the multidisciplinary care
of the patient with a suspected or confirmed diagnosis of COVID-19]. Acta Colombiana de Cuidado Intensivo. 2020; 20: 1-112.
doi: 10.1016/j.acci.2020.09.004

Complicaciones asociadas a COVID-19:

- Survival from in-hospital cardiac arrest in COVID-19 patients is 20% in those under 45
years of age, but 3% in those aged 80 or more.
- AKI requiring renal replacement therapy (RRT) is reported in >25% of COVID-19 patients
admitted to critical care, with a median duration of use being 8 days.
 - Seizures may occur in about 0.5% of hospitalised patients.
- Stroke (perhaps 1%, due largely to large vessel thrombotic/embolic occlusion) and
reduced consciousness (<15%) tend to occur late in the disease. Critical illness per se can
cause an axonal motor neuropathy.

Referencias bibliográficas:

- Chalmers JD, et al. Management of hospitalised adults with coronavirus disease-19

(COVID-19): A European Respiratory Society living guideline. European Respiratory Journal
Jan 2021, 2100048; DOI: 10.1183/13993003.00048-2021

https://erj.ersjournals.com/content/early/2021/03/07/13993003.00048-2021

- COVID-19 Clinical management: living guidance, 25 January 2021. WHO REFERENCE

NUMBER: WHO/2019-nCoV/clinical/2021.1

https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1

- Lamontagne F, et al. Practice Update to living WHO guideline on drugs for covid-19. BMJ
2020; 371 doi: https://doi.org/10.1136/bmj.m4475 (Published 20 November 2020)

https://www.bmj.com/content/371/bmj.m4475

- Cheng A, et al. Outpatient Management of COVID-19: Rapid Evidence Review. Am Fam

Physician. 2020 Oct 15;102(8):478-486.

https://www.aafp.org/afp/2020/1015/p478.html

- Consenso colombiano de atención, diagnóstico y manejo de infección COVID-19 en

establecimientos de salud, versión 12 abril 2020.

https://www.revistainfectio.org/index.php/infectio/article/view/853/905

- Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS

COV-2/COVID-19 en establecimientos de atención de la salud. Segunda Edición.
Recomendaciones basadas en consenso de expertos e informadas en la evidencia.
Sección VIII. Prevención y control de la infección por SARS-CoV-2/COVID-19. VOL. 24 (3)
SUPLEMENTO 2 2020, versión 06 junio 2020. http://dx.doi.org/10.22354/in.v24i3.872.

http://www.revistainfectio.org/index.php/infectio/issue/view/103

- GUÍA DE PRÁCTICA CLÍNICA (Colombia). Recomendaciones para el diagnóstico,

tratamiento y prevención de la neumonía adquirida en la comunidad en adultos
inmunocompetentes, versión 2013.
 https://www.elsevier.es/es-revista-infectio-351-articulo-recomendaciones-el-diagnostico-
tratamiento-prevencion-S0123939213700195

- YNHHS Treatment Guidance for Hospitalized ADULTS with COVID-19 last updated
10/27/20

https://covid.yale.edu/clinical/protocol/
- YNHHS Initial Treatment Algorithm for Hospitalized ADULTS with Non–Severe COVID-19 -
Algorithm last updated 4/27/20

https://files-profile.medicine.yale.edu/documents/e91b4e5c-ae56-4bf1-8d5f-
e674b6450847

- YNHHS Initial Treatment Algorithm for Hospitalized ADULTS with Non–Severe COVID-19 -
Algorithm last updated 6/22/20

https://medicine.yale.edu/intmed/COVID-19%20ADULT%20Treatment%20Algorithm
%206.22.20_389358_5_v1.pdf

- Recomendaciones de SEIMC sobre el uso de las pruebas de detección de anticuerpos, 27

de abril del 2020.

https://seimc.org/contenidos/documentoscientificos/recomendaciones/seimc-rc-2020-
Recomendaciones_uso_de_las_pruebas_de_deteccion_de_anticuerpos.pdf

- Lineamientos para el uso de pruebas diagnósticas de SARS-COV-2 (COVID-19) en Colombia,

versión 02, abril 2020.

https://www.minsalud.gov.co/Ministerio/Institucional/Procesos%20y
%20procedimientos/GIPS21.pdf

- NIH - COVID-19 Treatment Guidelines, Site Updated: April 21, 2020.

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Patients with COVID-19, Last updated April 21, 2020.

https://www.idsociety.org/globalassets/idsa/practice-guidelines/covid-19/treatment/idsa-
covid-19-gl-tx-and-mgmt-v1.0.4.pdf

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Published by IDSA on 4/11/2020. Last updated, 9/25/2020.

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covid-19-gl-tx-and-mgmt-v3.3.0.pdf

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https://sepsis-one.org/surviving-sepsis-campaign-guidelines-on-the-management-of-
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ATENCIÓN, DIAGNÓSTICO Y MANEJO DE LA INFECCIÓN POR SARS-COV-2/COVID-19 EN
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https://jamanetwork.com/journals/jama/fullarticle/2768351
ANEXOS:

Estudio sin grupo control, 143 pacientes, edad 56.5 +/- 14.6 años, 37% mujeres, 72.7%
presentaron neumonía, estancia hospitalaria 13.5 +/- 9.7 días, 7% requirieron ventilación
mecánica invasiva, seguimiento 60.3 +/- 13.6 días, 12.6 % con resolución completa de los
síntomas, 87.4% con persistencia de síntomas:

- 32% 1 o 2 síntomas.
- 55% 3 o más síntomas.
- Deterioro calidad de vida 44.1%
- Fatiga 53.1% - Disnea 43.4% - Artralgias 27.3% - Dolor torácico 21.7%
Huang C, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;
397: 220–32. Published Online January 8, 2021. https://doi.org/10.1016/S0140-6736(20)32656-8

Main characteristics of the included studies.

LDH is an intracellular enzyme found in cells in almost all organ systems, which catalyzes the interconversion of pyruvate and lactate,
with concomitant interconversion of NADH and NAD+. The enzyme is composed by two major subunits (i.e., A and B), and is present in
humans in five separate isozymes (LDH-1 in cardiomyocytes, LDH-2 in reticuloendothelial system, LDH-3 in pneumocytes, LDH-4 in
kidneys and pancreas, and LDH-5 in liver and striated muscle).

Lippi G, et al (2020). Laboratory abnormalities in patients with COVID-2019 infection, Clinical

Chemistry and Laboratory Medicine (CCLM), 58(7), 1131-1134. doi:
https://doi.org/10.1515/cclm-2020-0198
https://www.degruyter.com/view/journals/cclm/58/7/article-p1131.xml
INFORMACION COMPLEMENTARIA DE REMDESIVIR:

- Presentación vial: 100 mg.

- Indicación (IDSA):

Pacientes hospitalizados con COVID-19 severo.

 SaO2≤94% en aire ambiente o

 PaO2/FiO2<300 o
 Requerimiento de suplencia de Oxigeno o
 Frecuencia respiratoria ≥ 24/min o
- Criterios de exclusión:

COVID-19 leve (no evidencia de neumonía).

COVID-19 moderado (neumonía y SaO2>94% en aire ambiente).

Pacientes menores de 12 años (uso compasivo).

Pacientes menores de 40 kg (uso compasivo, impregnación 5 mg/kg – mantenimiento 2.5

mg/kg/día).

Embarazadas (uso compasivo).

Burwick RM, et al. Compassionate Use of Remdesivir in Pregnant Women with Severe Covid-19, Clinical Infectious Diseases, ciaa1466, https://doi.org/10.1093/cid/ciaa1466

Maldarelli GC, et al. Remdesivir Treatment for Severe COVID-19 in Third-Trimester Pregnancy: Case Report and Management Discussion, Open Forum Infectious Diseases,
Volume 7, Issue 9, September 2020, ofaa345, https://doi.org/10.1093/ofid/ofaa345

Tiempo de evolución de síntomas mayor a 12 dias.

Pacientes con enfermedad hepática grave: ALT o AST >5 veces el límite superior de la
normalidad (LSN).

Pacientes con insuficiencia renal y DCr <30 ml/min o terapia de reemplazo renal (hemodiálisis
o diálisis peritoneal) teniendo en cuenta contenido de Ciclodextrina.

- Dosis:
Impregnación: 200 mg IV.
Mantenimiento: 100 mg IV/día.
Reconstitución vial: 19 ml de agua esteril.
Dilución:
Impregnación en 250-350 ml de NaCl 0,9%.
Mantenimiento en 100-250 ml de NaCl 0,9%.
Tiempo perfusión: 30-120 minutos.

Tiempo tratamiento:

a. No ventilación mecánica: 5 días, extender a 10 dias si paciente no presenta mejoria

clinica.
b. Ventilación mecánica y/o ECMO: 10 dias.
Monitoreo toxicidad:
 Hemograma: diario.
Creatinina – BUN - Ionograma: diario.
ALT – AST – Bilirrubinas – Fosfatasa alcalina: diario.
- Interacciones de importancia clinica:
Rifampicina: ↓ concentraciones de Remdesivir 15-30% por inducción de CYP3A4, no se requiere ajuste de
dosis.
Inhibidores proteasa (ATV/r o DRV/r o LPV/r): efecto neto no requiere ajuste de dosis.

Pharmacokinetics:

a. Peak: active metabolite 3-4 hours

b. Half-life: prodrug: ~ 1 hour, active metabolite ~ 24 hours

c. Distribution: Unbound 12.1%; Wide distribution, Poorly crosses blood-brain barrier

d. Metabolism: Prodrug activated by esterases and hydrolase; Active metabolite CYP3A4 substrate, possible CYP2D6,
CYP2C8, OAT1b1, and P-gp substrate in vitro, Remdesivir inhibits CYP3A4

e. Elimination: Renal 63%, biliary 27.8%

https://www.covid19-druginteractions.org/checker
Dr. Abraham Katime Zúñiga.
Especialista en Medicina Interna e Infectología.