Manejo Farmacológico de Pacientes Con Covid 20 Setiembre

• Por favor no abandone la sesión iniciaremos a la hora pactada
VERSIÓN 4.0: “ACTUALIZACIÓN EN EL MANEJO INTEGRAL DEL

PACIENTE CON COVID-19: DE LA VEHEMENCIA A LA EVIDENCIA”
Samuel Pecho Silva

Neumólogo Clínico y Ocupacional
Hospital Nacional Edgardo Rebagliati Martins - EsSalud
Egresado de la maestría en Epidemiología Clínica y Bioestadística
Maestrando en Ecografía Clínica para Emergencias y Cuidados Críticos
Diplomados en: Ecografía Especializada en paciente crítico 2019
Epidemiología Clínica, Auditoría Médica Basada en la Evidencia y en Salud
Ocupacional
Docente: UPCH – UDEP

Filiación científica: UCS
Sin conflictos que declarar
Lima, 20 de septiembre 2020

Es de sabios limitarse a comentar o criticar solo
aquellos aspectos que uno domina.
Rousseau decía: «recuerda siempre que nadie se extravía por no saber, sino porque
cree saber».
Antes de cometer alguno de los errores mencionados anteriormente, dejémonos guiar

por el sentido común y apliquemos el principio universal: in dubiis, abstine (en caso de
duda, abstenerse).
Arch Bronconeumol. 2020;56(4):197–198

Para esta 4ta versión: revisión narrativa
• Fueron 416 publicaciones seleccionadas
• 357 artículos utilizados
• Se ha evitado las siguientes falacias:

– Falacia ad verecundiam
– Falacia ad ignorantiam
Programa
 Medidas de Prevención, Transmisión y reinfección

 Antivirales, Antiinflamatorios, inmunomoduladores, plasma convaleciente
 Antibioticoterapia y Anticoagulación
 Terapia con Oxigeno: dispositivos de administración y pronación despierto
 ARDS (SDRA): conceptos básicos para el médico no intensivista
 Manejo Paliativo, Post-Covid, complicaciones y secuelas por COVID-19
 Casos Clínicos reales
Programa

Taxonomía
• Orden: nidoviridae o nidovirales
• Familia: coronaviridae
• Sub-familia: coronavirinae u orthocoronavirinae
• Género: 4
• Características
– Gran diversidad genética
– Capacidad de infectar a varias especies
– Alta frecuencia de mutaciones
– Inestabilidad de la RNA polimerasa
– Recombinación de RNA homólogo
Pradhan D et al. A Review of Current Interventions for COVID-19 Prevention, Archives of Medical Research
(2020), doi: https://doi.org/10.1016/j.arcmed.2020.04.020.
Género: 4 géneros de Coronavirus (CoV)
• Circulan y causan infecciones todo el año
– excepto: MERS, SARS-Cov-1, SARS-CoV-2
• Virus ARN con 4 géneros: los alfa y beta (mamíferos) y los

gamma y delta (aves y cerdos)
– 10 a 30% de resfríos comunes, rinitis, faringitis, laringitis y en
menores de 1 año bronquitis, bronquiolitis, neumonía
Género coronavirus
• Alphacoronavirus: Antes Grupo 1: murciélagos y humanos
• 1-a: CoV-229E y CoV-NL63
• 1-b: alfavirus 1
• Betacoronavirus: divididos en subgéneros o linajes. Antes Grupo 2: humanos y
murciélagos.
• Linaje A (embecovirus): CoV-OC43 y CoV-HKU1
• Linaje B o subgrupo 2B (Sarbecovirus):
– Subgrupo 2b: SARS-Cov-1 y SARS-Cov-2: pandémicos y un subgrupo 2-a: coronavirus murino y virus de la
hepatitis del ratón
• Linaje C (Merbecovirus): MERS y coronavirus de murciélagos: esporádicos brotes en Arabia
• Linaje D (Nobecovirus): Sólo de murciélagos
• Hibecovirus: Bat Hp-betacoronavirus Zhejiang2013
• Gammacoronavirus: virus aviares
• Deltacoronarivus: virus porcinos
October 2020 Volume 33 Issue 4 e00028-20
E. Ortiz-Prado et al. / Diagnostic Microbiology and Infectious Disease 98 (2020) 115094
Immunity 52, June 16, 2020
JAMA. doi:10.1001/jama.2020.12839
JAMA. doi:10.1001/jama.2020.12839
JAMA. doi:10.1001/jama.2020.12839
Transmisión
SARS-Cov-2: de 2 a 14 días, en promedio 5 a 7 días
https://www.news-medical.net/health/Coronavirus-Incubation-Period.aspx
Historia Natural de la infección por SARS-Cov-2
Exposición a paciente con SARS-Cov-2
No infección (10-30%) Infección (70-90%)
Asintomático: 40% Sintomático (60%)

Subclínico: 50-60% Presintomático
Leve: 80% Moderado: 10% Severo:5%

Crítico: 5%
Letalidad Global: 0.6-2% Hospitalización: 20%

Cuidados Críticos: 1/16 000
Mortalidad en hospitalizados: 40% - 60%
J.M. Pericas et al. European Heart Journal (2020) 41, 2092–2108 doi:10.1093/eurheartj/ehaa462
Hasan K. Siddiqi y col. International Society for Heart and Lung Transplantation. Doi: 10.1016/j.healun.2020.03.012
J.M. Pericas et al. European Heart Journal (2020) 41, 2092–2108 doi:10.1093/eurheartj/ehaa462
Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2 [published online ahead of print, 2020
May 6]. JAMA. 2020;10.1001/jama.2020.8259. doi:10.1001/jama.2020.8259
Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review [published online ahead of
print, 2020 Jun 3]. Ann Intern Med. 2020;M20-3012. doi:10.7326/M20-3012
Chau NVV, Thanh Lam V, Thanh Dung N, et al. The natural history and transmission potential of asymptomatic SARS-CoV-
2 infection [published online ahead of print, 2020 Jun 4]. Clin Infect Dis. 2020;ciaa711. doi:10.1093/cid/ciaa711
Asintomático a presintomático
• Asintomáticos con lesiones pulmonares: hasta 54% (subclínico)
• Asintomático a sintomático: 0 a 10.3% a 88.9%
Transmisión
• La transmisión presintomática: 44% (25-69%)
• Si la transmisión presintomática es mayor al 30%
– Con un R0 de 2.5: no basta el aislamiento a menos que el 90% de
contactos sean rastreados
– Los síntomas en los contactos pueden aparecer antes que en los
casos
• Intervalo de serie: aparición de síntomas entre casos sucesivos en una cadena
de transmisión: 5.8 días
• Periodo de incubación: tiempo entre la infección y la aparición de síntomas:
5.2 días
Incubación Fase I Fase II Fase III Fase IV Fase V
Infección Pulmonar Hiperinflamación Recuperación Secuelar
Temprana
IIA IIB
Fase Viral
Fase inflamatoria
Asintomáticos: 40%
Leve/moderado: 90%
5.2 – 6.4 días 7 días Moderado/severo: 15%
2.1 – 14 días (4-14) Crítico: 5%
21 a 30 días
7 a 21 días
Replicación detectable 2 días antes de síntomas hasta 30 días del inicio de síntomas 1 a 6 meses
La detección más allá del día 8 de los síntomas no suele asociarse a transmisión
En casos leves este periodo se acorta a 4 a 5 días
En casos severos este periodo puede extenderse hasta la muerte Autor: Samuel Pecho
Se ha logrado detectar a un día de la infección en estudios de investigación
Incubación Fase I Fase II Fase III Fase IV Fase V
Infección Pulmonar Hiperinflamación Recuperación Secuelar
Temprana
IIA IIB
Fase Viral
Fase inflamatoria
Asintomáticos: 40%
Leve/moderado: 90%
5.2 – 6.4 días 7 días Moderado/severo: 15%
2.1 – 14 días (4-14) Crítico: 5%
21 a 30 días
7 a 21 días
1 a 6 meses
Conversión: 14 días
Total positivos: 21 días IgA e IgM: inicia su presencia a los 6 a 8 días. Alcanza pico: 2-3 semana
Juntos pico: 8 – 15 días Mínimo valor a las 5 semanas. Desaparece completamente: 7 semanas
Picos: variables
IgG: inicia su presencia a los 10 a 14 días. Alcanza un pico a las 3 semanas. Disminuye a
Persistencia: homogénea
la semana 5: puede permanecer hasta 6 meses y se estima que dure 1 año
Yu H-qiong et al. Distinct features of SARS-CoV-2-specific IgA response in COVID-19 patients. Eur Respir J 2020; 56: 2001526
[https://doi.org/10.1183/13993003.01526-2020].
A robust memory B-cell and plasmablast expansion is detected early in infection,2,4 with secretion of serum IgM and
IgA antibodies by day 5 to 7 and IgG by day 7 to 10 from the onset of symptoms. In general, serum IgM and IgA titers
decline after approximately 28 days, and IgG titers peak at approximately 49 days.
Published online September 11, 2020Downloaded From: https://jamanetwork.com/ on 09/19/2020

Antibodies attacking SARSCoV2 virus. Illustration Credit:
Kateryna Kon /Shutterstock
Individuals in bus 2 had a 34.3%(95%CI,24.1%-46.3%) higher risk of getting COVID-19 compared
with those in bus 1 and were 11.4 (95%CI, 5.1-25.4)
JAMA Intern Med. doi:10.1001/jamainternmed.2020.5225

Published online September 1, 2020.
doi/10.1093/cid/ciaa1249/5896916 by guest on 30 August 2020
Predicting Infectious SARS-CoV-2 • cid 2020. DOI: 10.1093/cid/ciaa638:
28 agosto 2020
https://www.thoracic.org/about/newsroom/press-releases/journal/2020/ats-statement-on-latest-covid-19-policy-actions.php
BMJ2020;370:m2516 http://dx.doi.org/10.1136 bmj.m2516
https://webedition.sanfordguide.com/en/sanford-guide-online/disease-clinical-condition/coronavirus
Intervención Reducción Intervalo
Del R
Máscara en algunos 2% -14 – 16%
lugares públicos
Reuniones con menos 2% -20-20%
de 1000 personas
Reuniones con menos 21% 1-39%
de 100 personas
Reuniones con menos 36% 16-53%
de 10 personas
Cierre de negocios de 31% 13-46%
alto riesgo
Cierre de negocios no 40% 22-55%
esenciales
Cierre de escuelas 39% 21-55%
universidades
Permanencia 18% 4-31%
obligatoria en casa
medRxiv preprint doi: https://doi.org/10.1101/2020.05.28.20116129

Scientific Reports | (2020) 10:12567 | https://doi.org/10.1038/s41598-020-68862-x
www.thelancet.com Vol 395 May 30, 2020
Pecho-Silva et al. | J Pure Appl Microbiol | 14(suppl 1):713-716 | May 2020
Pradhan D et al. A Review of Current Interventions for COVID-19 Prevention, Archives of Medical Research
(2020), doi: https://doi.org/10.1016/j.arcmed.2020.04.020.
www.thelancet.com Vol 395 June 27, 2020
Nussbaumer-StreitB et al. Quarantine alone or in combination with other public health measures to control COVID-19:
a rapid review. Cochrane Database of Systematic Reviews 2020, Issue 4. Art. No.: CD013574.
DOI: 10.1002/14651858.CD013574
Critical Care Medicine. DOI:
https://www.jwatch.org/na52247/2020/09/10/masks-prevent-viral-respiratory-infections?ijkey=F-Lafd-EF
Sohil Khan et al. Expert Opinion on Pharmacotherapy.
Published online: 04 Aug 2020. DOI:
10.1080/14656566.2020.1792884
Fisher KA, Tenforde MW, Feldstein LR, et al. Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults ≥18 Years in 11
Outpatient Health Care Facilities — United States, July 2020. MMWR Morb Mortal Wkly Rep 2020;69:1258–1264. DOI:
http://dx.doi.org/10.15585/mmwr.mm6936a5
https://www.medscape.com/viewarticle/937174?src=soc_fb_200912_mscpedt_news_mdscp_coronavirus&faf=1#vp_1
aOR and 95% CI for community exposures associated with confirmed COVID-19 among symptomatic
adults aged ≥18 years (N = 314) — United States, July 1–29, 2020
Adjusted odds ratio

MMWR / September 11, 2020 / Vol. 69 / No. 36
Ejemplo:
For H1N1 influenza, contact
tracing was estimated to
be 4,363 times more cost-
effective than school closures
($2,260 vs. $9,860 per death
prevented).
medRxiv preprint doi: https://doi.org/10.1101/2020.04.20.20054726.this version posted June 15, 2020.

A reevaluation in 40 family members
33.6 ± 2.7 days after the first
evaluation, show the persistence of
positive IgM and IgG in the 20 positive
cases in the first evaluation.
Having a primary case of COVID-19 in

home, the secondary attack rate of this
infection is 53%
medRxiv preprint doi: https://doi.org/10.1101/2020.09.06.20189456.this version posted September 9, 2020

Considerando la alta ocurrencia de COVID-19 en el Perú, los bajos niveles de saturación de oxígeno
evidenciados en la admisión hospitalaria, parte de la cual podría explicarse por el fenómeno de
hipoxemia “silenciosa”, y el mal pronóstico de los pacientes que buscan atención médica tardía,
cuando los niveles de saturación de oxígeno son muy bajos, con base a la evidencia actualmente
disponible, es razonable recomendar el uso domiciliario del pulsioxímetro de dedo para la
monitorización remota de los niveles de saturación de oxígeno en pacientes con COVID-19
catalogados inicialmente como casos leves y con factores de riesgo.
Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS
positive test in the younger participants (OR = 0.61, 95% CI 0.41–0.91; OR = 0.85,95%CI 0.74–0.98; respectively).
A significantly lower probability of a positive test result was detected in the individuals 65 years who received anti-
pneumococcal vaccination (OR = 0.56, 95%CI 0.33–0.95).
These results need to be confirmed by further investigations, but they are relevant given the probable
coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn–winter season
Vaccines 2020, 8, 471; doi:10.3390/vaccines8030471

¿Reinfecciones?
Autor Casos Probables Referencia
Batisse et al. 11 Clinical recurrences of COVID-19 symptoms after recovery: viral relapse,
reinfection or inflammatory rebound? J Infect. 2020 Jun 30S0163-4453(20)30454-
0. doi: 10.1016/j.jinf.2020.06.073 .
Lafaie et al. 3 Recurrence or Relapse of COVID-19 in older patients: a description of three cases.
J Am Geriatr Soc 2020 1 August
Lan et al. 1 Positive RT-PCR test results in patients recovered from COVID-19. JAMA 2020; 323
:1502–3 .
Tomassini et al. 6 https://doi.org/10.1016/j.jinf.2020.08.011
0163-4453
Kai-Wang To 1 (Real) https://academic.oup.com/cid/advance-
142 días después article/doi/10.1093/cid/ciaa1275/5897019 by guest on 06 September 2020
Diferente clades/lineages
Reinfection of COVID-19 is possible. Studies indicate that about 10% of people with mild infections show little immune
response, increasing their risk for reinfection.
Tomassini et al. Possible SARS-CoV-2 reinfection / Journal of Infection xxx (xxxx) xxx
https://www.medscape.com/viewarticle/936574?src=soc_fb_200902_mscpedt_news_mdscp_whyte&faf=1
Distribución de Síntomas de Covid-19
• Un 40% síntomas leves: fiebre, tos, disnea, mialgia o artralgia, odinofagia, fatiga, diarrea y
cefalea
• Un 40% síntomas moderados: neumonía
• Un 15% síntomas graves: neumonía severa que requieren soporte de oxígeno
• Un 5% cuadro clínico crítico presentando una o más de las siguientes complicaciones:

• IRA, SDRA, sepsis y choque séptico, TVP/TEP y alteraciones de la coagulación y/o falla
multiorgánica, incluyendo insuficiencia renal aguda, insuficiencia hepática, insuficiencia cardiaca,
shock cardiogénico, miocarditis, ACV
• También se han documentado complicaciones atribuidas a los procedimientos invasivos o no
invasivos, realizados durante el manejo clínico del caso.
Organización Panamericana de la Salud / Organización Mundial de la Salud. Alerta Epidemiológica: COVID-19, complicaciones y
secuelas. 12 de agosto de 2020, Washington, D.C. OPS/OMS.2020
Rev Bras Ter Intensiva. 2020;32(2):166-196
Australian guidelines for the clinical care of people with COVID-19 - Australian National COVID-
19 Clinical Evidence Taskforce
Australian guidelines for the clinical care of people
with COVID-19 - Australian National COVID-19
Clinical Evidence Taskforce
Historia Natural de la infección por SARS-Cov-2
Exposición a paciente con SARS-Cov-2
No infección (10-30%) Infección (70-90%)
Asintomático: 40% Sintomático (60%)

Subclínico: 50-60% Presintomático
Leve: 80% Moderado: 10% Severo:5%

Crítico: 5%
Letalidad Global: 0.6-2% Hospitalización: 20%

Cuidados Críticos: 1/16 000
Mortalidad en hospitalizados: 40% - 60%
https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html
Asintomáticos, Leves, Moderados
Severos / Críticos
Hasan K. Siddiqi y col. International Society for Heart and Lung Transplantation. Doi: 10.1016/j.healun.2020.03.012
This article was published on May 15,
2020, at NEJM.org.
DOI: 10.1056/NEJMcp2009575
Copyright © 2020 Massachusetts Medical Society
JAMA April 7, 2020 Volume 323, Number 13
Incremento de Disminución de
• Neutrophil • lymphocyte, monocyte, and eosinophil,

hemoglobin, platelet, albumin, serum
sodium,
• ALT, AST), BT, BUN
• Lymphocyte to C-reactive protein ratio
(LCR), leukocyte to C-reactive protein ratio
• Cr, VSG, PCR, PCT, DHL Fibrinógeno (LeCR), leukocyte to IL-6 ratio (LeIR),
• TP, Dímero D, glucosa, ratio N/L

• Sin cambios significativos: leucositos
totales, CPK, troponina I, mioglobina, IL-6V,
vitamina K
Ghahramani et al. Eur J Med Res (2020) 25:30

https://doi.org/10.1186/s40001-020-00432-3
• Median age was 66 years (53–68) and 292 (77%) were men.
• The main comorbidities included obesity and overweight (67%), hypertension (49.6%)
and diabetes (30.1%).
• Median time from disease onset (i.e., viral symptoms) to ICU admission was 8 (6–11)
days (missing for three)
Primera semana Segunda Tercera Mortalidad
semana semana Global
42.5% 45.6% 11.1% 26.4%
Mortalidad 37% 21% 12%
características SOFA más alto, trombocitopenia,
IRA, lesión pulmonar limitada, IL6,
EPOC, Edad, inmunocompromiso,
troponina
Intensive Care Med
https://doi.org/10.1007/s00134-020-06202-3
Pooled analysis show individuals with obesity
were more at risk:
• for COVID-19 positive, >46.0% higher (OR =
1.46; 95% CI,1.30–1.65; p < 0.0001)
• for hospitalization, 113% higher (OR = 2.13;
95% CI,1.74–2.60; p < 0.0001)
• for ICU admission, 74% higher (OR = 1.74;
95% CI,1.46–2.08)
• for mortality, 48% increase in deaths (OR =
1.48; 95% CI, 1.22–1.80;p < 0.001
Meta-analysis of the association between individuals with obesity and the risk of
testing positive for COVID-19
Popkin et al. Obesity Reviews. 2020;1–17

Saved from URL: https://www.news-medical.net/news/20200909/Scientists-explain-why-men-are-at-higher-risk-from-COVID-19.aspx
Pancreatitis, pericarditis, microinfarto suprarrenal, activación microglial
cerebral, que requieren mayor investigación para comprender su papel
en la fisiopatología del COVID-19 severo
DAD, trombosis, hemofagocitosis, deficiencia inmunitaria
Acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the
cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite
the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA
from paraffin sections was detected at least in one organ in 90% patients.
Recalde B et al. Thorax Epub ahead of print: [06/09/2020]. doi:10.1136/thoraxjnl-2020-215577

• Morbid obesity (adjusted odds ratio [OR], 2.30; 95% CI,1.77-2.98; vs no obesity; P < .001) and hypertension (adjusted OR,
2.36; 95%CI, 1.79-3.12; P < .001) were common and in addition to male sex (adjusted OR, 1.53; 95% CI, 1.20-1.95;P = .001)
were associated with greater risk of death or mechanical ventilation.
• Diabetes was associated with increased risk of this outcome in univariable analysis (OR, 1.82; 95% CI, 1.41-2.36;P < .001) but
did not reach statistical significance after adjustment (adjusted OR, 1.31; 95% CI, 0.99-1.73; P = .06).
• Patients with multiple risk factors (morbid obesity, hypertension, and diabetes) faced risks similar to 8862 middle-aged (age
35-64 years) nonpregnant adults with COVID-19 infection without these conditions
JAMA Internal Medicine Published online September 9, 2020

Early estimation of the risk factors for hospitalization and mortality by COVID-19 in Mexico
Data on 10,544
individuals
(57.68% men),
with mean age
46.47±15.62, were
analyzed
IMSS (Mexican Institute of Social Security). ISSSTE (Institute of Social Security and Services for State Workers). SSA (Health Ministry)
Carrillo-Vega et al. PLoS ONE 15(9): e0238905. https://doi.org/10.1371/journal.pone.0238905

The clinical course of COVID-19 in the outpatient setting:
a prospective cohort study
• Among 118 SARS-CoV-2 infected outpatients, the median age was 56.0 years (IQR, 50.0 to 63.0) and 50 (42.4%)
were male.
• Among those reporting active symptoms, the most common symptoms during the first week since symptom
onset included weakness/fatigue (67.3%), cough (58.0%), headache (43.8%), and sore throat (34.8%).
• Participants returned to their usual health a median of 20 days (IQR, 13 to 38) from the symptom onset, and only
65.5% of respondents were at their usual health during the fourth week of illness.
• Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization.
• Individuals at the same duration of illness had a 6.1 times increased adjusted odds of subsequent hospitalization
per every percent decrease in home SaO2 (95% confidence interval [CI]: 1.41 to 31.23, p=0.02).

Situación Mundial Actual
20 setiembre 2020
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
Perú Primero en el mundo en número de muertos / millón de habitantes

De los 5 países con mayor número de casos absolutos, Perú es el primero en número de casos /millón de habitantes
y el de menor población
https://www.worldometers.info/coronavirus/?#countries
https://www.medscape.com/viewarticle/937308?src=soc_fb_200916_mscpedt_news_mdscp_hospitalrisk&faf=1
• 545 asymptomatic healthcare workers were recruited while at work
• The point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545).
• The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516).
• Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%,  2=21.1034,
p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic.
• Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general
internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%).
• BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of
seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01).
• Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with
working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02).
Shields A et al. Thorax Epub ahead of print: [20/09/2020]. doi:10.1136/thoraxjnl-2020-215414

Chafloque-Vásquez R et al. Acta Med Peru. 2020;37(3). doi:https://doi.org/10.35663/amp.2020.373.1050
"Aunque el número de
médicos infectados en
Perú puede ser
considerado más bajo,
en comparación con
otros países de la
región, la tasa de
letalidad (CFR) de
médicos en Perú debido
a COVID-19 parece ser
más alto (~ 5%),
alcanzando valores aún
más altos en algunos
áreas del país“
German Valenzuela-Rodriguez, Lysien I. Zambrano, Fausto Muñoz-Lara, Samuel Pecho-Silva, Kovy Arteaga-Livias, Alfonso J. Rodriguez-Morales.
Intranational differences in the case fatality rates for COVID-19 among Peruvian physicians Int J Infect Dis. 2020 Sep 13;S1201-9712(20)30735-9. doi:
10.1016/j.ijid.2020.09.018
Tipo Proporción Características Clínicas
1 80-85% de pacientes sintomáticos Fiebre, cefalea, síntomas respiratorios leves, dolor de
garganta, no hipoxemia, radiografía normal, excelente
pronóstico
2 80% de los pacientes hospitalizados Leve hipoxemia, infiltrados menores bilaterales, un 15%
progresa rápido al tipo 3
3 15% de los hospitalizados Moderada a severa hipoxemia. Taquípnea. IL-6 y otros
marcadores inflamatorios elevados. Puede progresar al
tipo 4 o 5
4 2/3 de pacientes que necesitan VM Hipoxemia severa que requiere VM. Compliance
pulmonar normal. Buena respuesta al NO. Poco beneficio
con pronación. VT mayor 6 ml/Kg permitido. FR menor
20. PEEP: menor 10 cm H2O
5 1/3 de los pacientes que necesitan VM Procalcitonina elevada ARDS. Estrategias de ventilación
protectiva y pronación están indicadas. Conifecciones
Rello J, Storti E, Belliato M, et al. Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers. Eur Respir J 2020; in press
(https://doi.org/10.1183/13993003.01028-2020).
Cite this as: BMJ 2020;370:m2911 http://dx.doi.org/10.1136/bmj.m2911
• The researchers found that 1.5% of people in cluster 1 and 4.4% of people in cluster 2 required respiratory support.
• Cluster 3 has stronger gastrointestinal symptoms and a need for respiratory support in 3.7%.
• The associated rate of hospital visits, however, was high in cluster 3 (23.6%) compared with clusters 1 and 2 (16.0% and 17.5%).
• Clusters 4, 5, and 6 included participants reporting more severe symptoms of covid-19 with 8.6%, 9.9%, and 19.8% requiring respiratory
support, respectively.
• Nearly half of the patients in cluster 6 ended up in hospital (45%), compared with just 16% of those in cluster 1.
Symptom clusters in Covid19: A potential clinical prediction tool from the
COVID Symptom study app
35 463 patients were included in the derivation
dataset (mortality rate 32.2%) and 22 361 in the
validation dataset (mortality rate 30.1%).
BMJ2020;370:m3339
http://dx.doi.org/10.1136/bmj.m3339
At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%e85%), 76%
(70%e81%), 69% (60%e74%) and 85% (80%e89%), respectively
Bartoletti M et al., Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection:
a multicentre cohort study (PREDI-CO study), Clinical Microbiology and Infection, https://doi.org/10.1016/j.cmi.2020.08.003
Mujer de 21 aumento de la
dísnea, cambios en la
coloración del esputo,
malestar, cefalea.
IgM e IgG: Negativo
PCR: Pendiente
¿Covid?
Programa

 Antivirales, Antiinflamatorios, inmunomoduladores, plasma
convaleciente
 La evidencia clínica, afortunadamente, ya no se basa en anecdóticas
series de casos. Con el auge de la llamada medicina basada en la
evidencia sobresale un diseño: el metaanálisis.
 El metaanálisis se define como una técnica de revisión que se utiliza para

identificar de modo sistemático, así como para valorar y combinar
estadísticamente todos los estudios sobre el mismo tema, tratándose
generalmente de una relación entre factor de exposición y enfermedad
Arch Bronconeumol. 2020;56(4):197–198

Deficiencias Observadas
 Falta de conocimientos básicos en evaluación crítica de la evidencia
 Necesidad de “hacer algo” o “dar algo”
 Falta de estandarización en la recolección de la información
 La idea de una “medicina de guerra” o de “médicos covid” o de “
médicos de primera línea” frente a los “teóricos”
 El mejor médico: experticia previa, evaluación de la evidencia,
implementación de ambas de manera dinámica
CMAJ 2020. doi: 10.1503/cmaj.200648; early-released April 29, 2020
Lopinavir - Ritonavir
 Mechanism of Action: Lopinavir and ritonavir may bind to Mpro, a key enzyme for
coronavirus replication. This may suppress coronavirus activity
Tim Smith et al. COVID-19 Drug Therapy – Potential Options. Elsevier © 2020
randomized, controlled, open-label trial. Hospitalized. confirmed SARS-CoV-2. respiratory illness. oxygen saturation of 94%
or less. PaO2/ FiO2 of less than 300 mm Hg. 1:1 ratio to receive: lopinavir/ritonavir (400/100 mg BID x 14d) in addition to
standard care, or standard care alone. Treatment with lopinavir–ritonavir was not associated: clinical improvement (HR:
1.24; 95% [CI], 0.90 to 1.72). Mortality at 28 days: 19.2% vs. 25.0%. Detectable viral RNA at various time points were
similar. clinical improvement that was shorter by 1 day than that observed with standard (HR 1.39; 95% CI, 1.00 to 1.91).
B. Cao, DOI: 10.1056/NEJMoa2001282

Diseño y Resultados:
Feb 10 and March 20, 2020
127 patients. 86: combination group and 41: control group.
The median number of days from symptom onset to
start of study treatment was 5 days (IQR 3–7).
The combination group: negative nasopharyngeal swab (7
days [IQR 5–11]) than the control group (12 days [8–15];
hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010).
Adverse events included self-limited nausea and diarrhoea
with no difference between the two groups. One patient in
the control group discontinued lopinavir–ritonavir because
of biochemical hepatitis. No patients died during the study.
Casos leves/moderados en los primeros 7 días
www.thelancet.com Published online May 8, 2020 https://doi.org/10.1016/S0140-6736(20)31042-4

Hugo Farne et al. Repurposing Existing Drugs for the Treatment of COVID-19. Published July 21, 2020 as
10.1513/AnnalsATS.202005-566FR
CMAJ 2020 May 19;192:E536-45. doi: 10.1503/cmaj.200648; early-released April 29, 2020
Lpv/Rtv SoC P-Value
Pacientes 1596 3376
Mortalidad 28 d 22.1% 21.3% 0.58
No reducción de mortalidad y No evidencia de efecto beneficio para disminuir la progresión a VM o

estancia hospitalaria.
OMS: el 4 de julio suspende el brazo lopinavir/ritonavir del Estudio Solidarity

Australian guidelines for the clinical care of people with
COVID-19 - Australian National COVID-19 Clinical Evidence
Taskforce
Remdesivir
• Antiviral creado por la empresa Gilead, que aún tiene la patente y actúa contra varios virus in-vitro e in-vivo:
activo contra el ébola, mers, el sars, y el sars-cov2
• Mecanismo de acción: Se une a la polimerasa de ARN y actúa como terminador de cadenas de ARN. It acts
as an adenosine analogue to interfere with viral RNA dependent RNA-polymerase (RdRp) and induce
premature or delayed RNA chain termination, whilst evading viral exoribonuclease activity
• Baja toxicidad por su especificidad al ARN viral, pruebe producir eventos adversos renales
• Tiempo de vida media prolongado permite el uso diario. A dosis establecidas de: 200 m ev el primer día y
luego 100 mg ev por 9 días para un total de 10 días.
• Se espera en Perú un costo de 600 dólares por ampolla (extra-oficial)
• Estaría indicado en Covid-19 moderado o severo hospitalizado usando oxígeno
Hugo Farne et al. Repurposing Existing Drugs for the Treatment of COVID-19. Published July 21, 2020 as 10.1513/AnnalsATS.202005-566FR
Remdesivir (GS-5734):
 Remdesivir is a monophosphoramidate prodrug of remdesivir-triphosphate (RDV-
TP), an adenosine analog that acts as an inhibitor of RNA-dependent RNA
polymerases (RdRps).
 Remdesivir-TP competes with adenosine-triphosphate for incorporation into nascent
viral RNA chains. Once incorporated into the viral RNA at position i, RDV-TP
terminates RNA synthesis at position i+3.
 Because RDV-TP does not cause immediate chain termination (i.e., 3 additional
nucleotides are incorporated after RDV-TP), the drug appears to evade proofreading
by viral exoribonuclease (an enzyme thought to excise nucleotide analog inhibitors).
• A case series of 61 hospitalized patients treated with remdesivir off license
reported a clinical improvement in 36 out of 53 patients with sufficient data to
analyze, although without a control group it is difficult to interpret these findings.
• Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate Use of Remdesivir for
Patients with Severe Covid-19. The New England journal of medicine 2020.
• An initial randomized controlled trial (RCT) was inconclusive, with a non-

significant trend towards reduced time to clinical improvement favoring
remdesivir. This trial was underpowered, with recruitment ending prematurely at
237 out of an intended 453 patients following the end of the outbreak in Wuhan.
• Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a
randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395(10236):1569-1578.
10.1513/AnnalsATS.202005-566FR
Wang et al. www.thelancet.com Vol 395 May 16, 2020
Efficacy and harms of remdesivir for the treatment of
COVID-19: a systematic review and meta-analysis
Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive
ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63-0.94).
AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to
high risk in RCTs.
Interpretation: There is paucity of adequately powered and fully reported RCTs evaluating effects of
remdesivir in adult, hospitalized COVID-19 patients.
Remdesivir should not be recommended for the treatment of severe COVID-19.
Piscoya y col. https://doi.org/10.1101/2020.05.26.20109595

Diapositivas tomadas de presentación del Dr. José María Miró
Remdesivir
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines.
National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/.
Dr. Topol Dr. Hahn
Sobre Remdesivir: The third breach of evidence-based data was your EUA issued August 28, 2020 broadening the remdesivir
approval to include any patient hospitalized with moderate COVID-19. There are insufficient data to support this approval, as it is
based on small, open-label studies with subjective endpoints. Remdesivir is an expensive drug, costing approximately $3000 per
treatment, in short supply, and even its approval for severe COVID-19 was based on time to recovery in a relatively small trial of just
over 1000 patients
https://www.medscape.com/viewarticle/936611?src=soc_fb_200904_mscpedt_news_mdscp_openletter&faf=1#vp_1
Favipiravir (Avifavir)
 is a guanine analogue that selectively inhibits RNA-dependent RNA
 polymerase (RdRP) of RNA viruses and has been approved for the treatment of novel
influenza since 2014
 Antiviral oral utilizado para influenza ( Japón) y Ébola
 Japón: ECA Fase III
 EUA: ECA Fase II
 India: ECA Fase III: favipiravir y umifenovir
Journal of the Chinese Medical Association Publish Ahead of Print

Favipiravir
 An open-label non-randomized trial in China found a significantly shorter time to
viral clearance (4 days [IQR 2.5 – 9] vs. 11 days [IQR 8 – 13]) and greater
improvement in chest radiographic appearances in patients with SARS-CoV-2 treated
with favipiravir/interferon(IFN)-α (n = 35) compared to lopinavir/ritonavir/IFN-α (n
= 45).
 Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with
Favipiravir for COVID-19: An Open-Label Control Study. Engineering; 2020 [accessed
Available from:https://dx.doi.org/10.1016/j.eng.2020.03.007.
10.1513/AnnalsATS.202005-566FR
• AVIFAVIR 1600 mg BID on Day 1 followed by 600
mg BID on Days 2-14 (1600/600 mg)
• AVIFAVIR 1800 mg BID on Day 1 followed by 800
mg BID on Days 2-14 (1800/800 mg)
• SOC.

Australian guidelines for the clinical care of people with COVID-19 -
Australian National COVID-19 Clinical Evidence Taskforce
Plasma convalecente
 Momento de la toma del plasma
 Tomarlo a las pocas semanas de la recuperación
 Altos títulos de Ac. Neutralizantes
 Dosis
 Momento de la administración
 No basado sólo en Ac.
Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID-19. Nat Rev Immunol.
2020;20(6):339-341. doi:10.1038/s41577-020-0321-6
Wu, F. et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications.
Preprint at medRxiv https://doi.org/10.1101/2020.03.30.20047365 (2020)
Focosi D et al. Convalescent plasma therapy for COVID-19: state of the art. Clin Microbiol Rev 33:e00072-20.
https://doi.org/10.1128/CMR.00072-20.
Chenguang et al. JAMA. doi:10.1001/jama.2020.4783. Published online March 27, 2020.
Effect of Convalescent Plasma Therapy on Time to Clinical Improvement
in Patients With Severe and Life-threatening COVID-19
A Randomized Clinical Trial
Ly et al. JAMA. Published online June 3, 2020. doi:10.1001/jama.2020.10044

Plasma convalecente
 The only other evidence comes from isolated reports of the use of convalescent
plasma in COVID-19, with a meta-analysis finding
 Seven case series and one prospective single-arm study with a total of 32 participants.
With small numbers, a lack of control groups and a high risk of bias, no conclusions
could be drawn about efficacy, and whilst serious adverse events were infrequent, they
were not absent.
 47 studies are ongoing, including 22 RCTs.
 Valk SJ, Piechotta V, Chai KL, Doree C, Monsef I, Wood EM, et al. Convalescent plasma or hyperimmune
immunoglobulin for people with COVID-19: a rapid review. Cochrane Database Syst Rev 2020;5:Cd013600
10.1513/AnnalsATS.202005-566FR
Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID19: Initial Three-
Month Experience
https://www.news-medical.net/news/20200814/Preliminary-Mayo-Clinic-results-from-convalescent-
plasma-in-35322-patients.aspx
https://www.livescience.com/fda-authorization-plasma-therapy-for-covid.html
Dr. Topol Dr. Hahn
Sobre Plasma Convalescente: That is a grossly insufficient correction and does not represent the truth. Here's what you
didn't say: There are no data or evidence from prospective, randomized trials for convalescent plasma to support any survival
benefit
https://www.thoracic.org/about/newsroom/press-releases/journal/2020/ats-statement-on-latest-covid-19-policy-actions.php
Plasma exchange in critically ill COVID-19 patients improved inflammation,
microcirculatory clot formation, and hypotension, thereby improving clinical
outcomes: fact or fiction?
• PE has a cutoff of 1,000, 000 daltons (Da) and can therefore remove many substances
• The inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6). CRP, in its pentameric form,
has a molecular weight of 120,000 Da and in its monomeric form 22,000 Da. IL-6 has a molecular weight
of 21,000 Da.
• It stands to reason that these two inflammatory molecules will be easily removed by PE.
• Reduction of the plasma level of inflammatory mediators via the use of PE does not necessarily equate to
an improvement in the septic status of the patient. It is simply an artificial reduction, “treating the
numbers” so to speak.
• The same is true for ferritin (474,000 Da), LDH (144,000 Da), and D-dimers (180,000 Da), where the
observed reduction is simply a consequence of removal and not an improvement of the patient’s
condition
• PE will remove the protective antibodies formed by the patient, which is not desirable
Honore et al. Critical Care (2020) 24:551
https://doi.org/10.1186/s13054-020-03262-1
• This retrospective, propensity score–matched case–control
study assessed the effectiveness of convalescent plasma
therapy in 39 patients with severe or life-threatening COVID-19
at The Mount Sinai Hospital in New York City.
• Oxygen requirements on day 14 after transfusion worsened in

17.9% of plasma recipients versus 28.2% of propensity score–
matched controls who were hospitalized with COVID-19
(adjusted odds ratio (OR), 0.86; 95% confidence interval (CI),
0.75–0.98; chi-square test P value = 0.025).
• Survival also improved in plasma recipients (adjusted hazard

ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027)
https://doi.org/10.1038/s41591-020-1088-9
Haemophagocytic lymphohistiocytosis (HLH)
Is a hyperinflammatory syndrome, which can lead to a cytokine storm, tissue

damage and multi-organ failure. It has a high mortality rate. Primary HLH is an
inherited condition, which presents mainly in childhood and may be
associated with immunodeficiency. Secondary HLH (sHLH) usually occurs in
previously immunocompetent people and may be triggered by autoimmune
or autoinflammatory disease (when it is called macrophage activation
syndrome [MAS]), malignancy (especially haematological malignancy) or, most
often, infection (when it may be indistinguishable from sepsis).
Viral infections are the most common cause of secondary sHLH
www.nice.org.uk/guidance/es26
• CS is a critical life-threating condition requiring intensive care admission and having a quite high
mortality.
• CS is characterized by a clinical presentation of overwhelming systemic inflammation, hyperferritinemia,
hemodynamic instability, and multi-organ failure, and if left untreated, it leads to death.
• The trigger for CS is an uncontrolled immune response resulting in continuous activation and
expansion of immune cells, lymphocytes, and macrophages, which produce immense amounts of
cytokines, resulting in a cytokine storm. The CS clinical findings are attributed to the action of the
proinflammatory cytokines like IL-1, IL-6, IL-18, IFN-g, and TNF-a.
• The main contributors to the interplay of the cytokine storm are IL-6 and TNF-a. In the absence of an
immediate and appropriate therapeutic intervention, patients develop ARDS as a result of acute lung
damage followed by multi-organ failure and resulting in death.
Ragab D et al. (2020) The COVID-19 Cytokine Storm; What We Know So Far.Front. Immunol. 11:1446.doi: 10.3389/fimmu.2020.01446
• IL-1 receptor antagonist, anakinra, which is used in treatment of rheumatoid arthritis, was
proven to be helpful in cytophagic histiocytic paniculitis with secondary hemophagocytic
lymphohistiocytosis, a disease associated with severe CS.
• Tocilizumab is a recombinant humanized IL-6 receptor antagonist that interferes with IL-6
binding to its receptor and blocks signaling. Tocilizumab is used in treatment of rheumatoid
arthritis, juvenile idiopathic arthritis, giant cell arteritis, and has proven valuable in treatment
of CS triggered by CAR-T cell therapy for hematological malignancies.
• Downstream inhibitors of cytokines: JAK inhibitors, are also being explored in treating CS.
Ragab D et al. (2020) The COVID-19 Cytokine Storm; What We Know So Far.Front. Immunol. 11:1446.doi: 10.3389/fimmu.2020.01446
Tratamiento antiinflamatorio
• Corticosteroides
• Inhibidores de la IL-6
• Tocilizumab, sarilumab, siltuximab
• Inhibidores de la IL-1
• Anakinra
• Inhibidores del JAK
• Baricitinib
• Inhibidores de la tirosin-cinasa de Bruton
• Acalabrutinib (inhibidores de la entrada)
• Bloqueadores del GM-CSF: mavrilimumab
• Colchicina (inhibidores de la entrada)
Interferons (IFNs): type I (IFN-α and-β) and III (IFN-λ)
• Both SARSCoV-2 and SARS-CoV can delay and/or reduce type-I IFN signaling and thus replicate to high viral titers
• IFN deficiencies may partly explain the striking high mortality in the elderly in COVID-19.
• IFNs were discovered in 1957, when Lindenmann and Isaacs observed that chicken embryos stimulated with heat-killed
viruses released a soluble product that “interefered” with influenza virus replication
• Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, et al. Interferons at age 50: past, current and
future impact on biomedicine. Nat Rev Drug Discov 2007;6(12):975-990.
• A recent in vitro study suggests SARS-CoV-2 may be more susceptible to IFN-α treatment than SARS-CoV, which the
authors attributed to differences in two of the viral proteins that antagonize IFN.(51) Several trials of recombinant IFN
therapy are in progress. IFN treatment will need to be carefully balanced against the potential for these drugs to promote
pulmonary vascular disease.
• Lokugamage K, Schindewolf C, Menachery V. SARS-CoV-2 sensitive to type I interferón pretreatment. bioRxiv; 2020
[accessed Available from: https://www.biorxiv.org/content/10.1101/2020.03.07.982264v1.full.
• George PM, Oliver E, Dorfmuller P, Dubois OD, Reed DM, Kirkby NS, et al. Evidence for the involvement of type I
interferon in pulmonary arterial hypertension. Circ Res 2014;114(4):677-688.
Hugo Farne et al. Repurposing Existing Drugs for the Treatment of COVID-19. Published July 21, 2020 as 10.1513/AnnalsATS.202005-566FR
De los resultados reportados en los estudios incluidos se puede concluir que existe incertidumbre acerca del
balance riesgo beneficio del uso de interferón lo cual no permite sustentar una recomendación a favor del uso
de esta droga pues el beneficio que conferiría es incierto, prevaleciendo la precaución ante los posibles
eventos adversos, los cuales son ya conocidos y han sido reportados ampliamente en la literatura.
Por ello, y en línea con las recomendaciones emitidas por organismos internacionales, el IETSI no
recomienda el uso de interferón como tratamiento o profilaxis para pacientes con COVID-19, fuera de un
contexto de ensayo clínico.
Inhibidores de la IL-6
• Sarilumab (Kevzara) de Sanofi y Renegeron

• Fase II: no beneficios en severos y críticos
• Severos no beneficio incluso riesgos
• Críticos
• Disminución de PCR
• Muerte: 23% vs 27%
• Permanencia en VM: 9% vs 27%
• Mejoría clínica: 59% vs 41%
• Destete de oxígeno y alta de uci: 58 y 53% versus 41%
• Tocilizumab: 2765 dólares por 400 mg
• TZLS-501 en desarrollo
Tocilizumab
• Inhibits IL-6-mediated signaling by competitively binding to both
soluble and membrane-bound IL-6 receptors.
• IL-6 is a proinflammatory cytokine that is involved in diverse
physiological processes such as T-cell activation,
immunoglobulin secretion induction, hepatic acute-phase
protein synthesis initiation, and hematopoietic precursor cell
proliferation and differentiation stimulation.
• IL-6 is produced by various cell types, including T- and B-cells,
lymphocytes, monocytes, and fibroblasts.
• The search was performed in and ranged up to April 18, 2020
• The published clinical experience with these drugs in COVID-19, with the few descriptive reports
• and case series, is very limited.
• Despite the data from some case series, the lack of a comparison group limits its interpretation until
rigorous data are available. For this reason, the results of the ongoing clinical trials to assess the role
of IL-6 blockade in COVID-19 are essential.
J. Solis-García del Pozo et al. European Review for Medical and Pharmacological Sciences
Capra et al. European Journal of Internal Medicine 76 (2020) 31–35
https://academic.oup.com/cid/article-abstract/doi/10.1093/cid/ciaa954/5870306
Microorganisms 2020, 8, 695; doi:10.3390/microorganisms8050695
Debido a que la evidencia disponible a la fecha (13 de julio de 2020) consiste en un ensayo clínico que
tuvo que ser detenido porque en su primer análisis interino no encontró beneficio clínico atribuible a
tocilizumab y estudios observacionales que, aunque numerosos, presentan resultados inconsistentes,
dadas las limitaciones metodológicas propias de este tipo de estudios, el IETSI mantiene su posición que
no es posible determinar el balance riesgo-beneficio de tocilizumab en pacientes con COVID-19, por lo
que no se puede justificar su uso fuera de ensayos clínicos
https://doi.org/10.1016/j.ijantimicag.2020.106103
Inhibidores de la IL-1
• Anakinra
• Un estudio en Italia:
• A 21 días sobrevida: 90% vs 56% (p=0.009)
• Un estudio en París
• Admisión en UCI para VM o muerte
• 25% vs 73% (versus grupo histórico, HR: 0.22 p< 0.0001)
• Para muerte sola: HR: 0.3 (p=0.0063)
• VM sola: HR: 0.22 p=0.0015
Anakinra
• Recombinant interleukin-1 (IL-1) receptor antagonist that blocks the biologic activity of natural
IL-1 by competitively inhibiting the binding of IL-1 to the interleukin-1 type receptor (Kineret
summary of product characteristics).
• IL-1 is a proinflammatory mediator produced in response to infection and is central to the
hyperinflammation seen in cytokine storm syndromes such as sHLH
• Anakinra is licensed as a subcutaneous injection for treating adults with rheumatoid arthritis,
and people aged at least 8 months with Still's disease or cryopyrin-associated periodic
syndromes (Kineret summary of product characteristics). It is not licensed for sHLH or for
intravenous administration.
• No studies were found considering the effectiveness, safety or cost effectiveness of anakinra
in adults and children with sHLH triggered by SARS-CoV-2 or a similar coronavirus
www.nice.org.uk/guidance/es26
https://webedition.sanfordguide.com/en/sanfor
d-guide-online/disease-clinical-
condition/coronavirus
Corticosteroides
• Potencialmente efectivos en SDRA no infeccioso
• Incrementan la mortalidad en neumonía relacionada a la influenza
• Algún beneficio en SARS y MERS pero con eventos adversos
• Incrementa la viremia y retarda el aclaramiento viral en SARS-Cov-2 y MERS
• El uso de corticoides: evidencia para su uso es inconsistente, confusa e
inconclusa. Está asociado a mayor mortalidad
1. www.thelancet.com Published online February 6, 2020 https://doi.org/10.1016/S0140-6736(20)30317-2

2. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-análisis. Journal of
Infection, https://doi.org/10.1016/j.jinf.2020.03.062
3. Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options. Open Forum Infectious Diseases
4. Grupo Peruano de Salud Respiratoria: 30 de abril y 1 de mayo 2020
A total of 5270 patients from 15 studies were included in this meta-analysis.
The result indicated that critical patients were more likely to require corticosteroids therapy (risk ratio [RR] = 1.56,95%
confidence interval [CI] = 1.28-1.90, P < 0.001).
Corticosteroid treatment was associated with:

Higher mortality (RR = 2.11, 95%CI = 1.13-3.94, P = 0.019)
Longer length of stay (weighted mean difference [WMD] = 6.31, 95%CI = 5.26–7.37, P < 0.001)
Higher rate of bacterial infection (RR = 2.08, 95%CI = 1.54–2.81, P < 0.001)
Hypokalemia (RR = 2.21, 95%CI = 1.07–4.55, P = 0.032)
Not hyperglycemia and nor hypocalcemia (RR = 1.35, 95%CI = 0.77–2.37, P = 0.302).
Z. Yang, J. Liu and Y. Zhou et al., The effect of corticosteroid treatment on patients with coronavirus infection: a
systematic review and meta-analysis, Journal of Infection, https://doi.org/10.1016/j.jinf.2020.03.062
• Corticoides: asociados a mayor
mortalidad en ARDS por inflluenza y
mayor riesgo de infecciones
• Eficacia de corticoides en ARDS y Shock
séptico: en debate
• Estudio restrospectivo con 201
pacientes en China con Covid-19: en
aquellos que desarrollaron ARDS el uso
de corticoide se asoció a menor
mortalidad. Sesgos y confusores para
definir el verdadero efecto protecto
• Corticosteroid use in subjects with SARS-CoV-2, SARSCoV, and
MERS-CoV infections delayed virus clearing and did not
convincingly improve survival, reduce hospitalization duration or
ICU admission rate and/or use of mechanical ventilation.
• There were several adverse effects.
• Because of a preponderance of observational studies in the
dataset and selection and publication biases our conclusions,
especially regarding SARS-CoV-2, need confirmation in
randomized clinical trials.
• In the interim we suggest caution using corticosteroids in persons
with COVID-19.
Leukemia https://doi.org/10.1038/s41375-020-0848-3
Sólo Metilprednisolona 40 mg al día por 10 días en
pacientes con ARDS por Covid-19
• Valorar bien riesgo versus beneficio
• Metilprednisolona 1 – 2 mg/Kg/día por 3 a 5 días o

menos
• Sociedad China: ≤ 0.5 – 1 mg/kg/día por máximo 7

días
No se
recomiendan los
corticoides
Published Online March 20, 2020 https://doi.org/10.1016/ S2213-2600(20)30127-2

Evitar uso innecesario de corticoides
www.thelancet.com/respiratory Published online April 6, 2020 https://doi.org/10.1016/S2213-2600(20)30161-2

Last updated June 22, 2020
Lu et al. Critical Care (2020) 24:241
https://doi.org/10.1186/s13054-020-02964-w
Multivariate analysis that

adjusted for major mortality-
associated variables and
propensity score indicated
that corticosteroid treatment
was independent from overall
mortality (adjusted OR 1.05;
95% CI 0.15–7.46)
Hydrocortisone equivalent
dosage 200 [range 100–800]
mg/day equivale a:
Metil: 20, 40, 160 mg
increased corticosteroid dosage was significantly associated with elevated mortality risk after adjustment for
administration duration (P = 0.003); every 10-mg hydrocortisone (2 mg metilprednisolona) increase in dosage was
associated with additional 4% mortality risk (adjusted HR 1.04, 95% CI 1.01–1.07).
Recovery Trial: Dexamethasone in Hospitalized
Patients with Covid-19 — Preliminary Report
• Dexametasona: 6 mg/día VO o EV – 8 junio se detuvo por el beneficio
• Equivale a 32 mg de MTP o 40 mg de prednisona
• En VM: se previene 1 muerte al tratar: 8
• En O2: se previene 1 muerte al tratar: 25
• Puede aumentar el riesgo en aquellos que no requieren oxígeno
Dexametasona SoC RR (95% IC)

Pacientes 2104 4321
Mortalidad 28 dias 22.9% 25.7% 0.83 (0.75-0.93) P < 0.001
En VM 29.3% 41.4% 0.64 (0.51-0.81) P=0.0003
O2 suplementario 23.3% 26.2% 0.82 (0-72-0.94) P=0.0021
No usuario de O2 17.8% 14% 1.19 (0.91-1.55) P=0.14
July 17, 2020 DOI: 10.1056/NEJMoa2021436 Horby PW. Recovery Trial June 16, 2020. medRxiv
https://www.epocrates.com/sites/epocrates/files/res/dacc/2020/COVID-19%20Consensus%20Full%2020200706.pdf
Dexametasona
BMJ2020;370:m2980
http://dx.doi.org/10.1136
bmj.m2980
Desenlace OR (95%IC) aOR (95%IC)
Mortalidad o VM 1.13 (0.73-1.75) 1.12 (0.67-1.88)
Mortalidad 1.13 (0.71-1.80) 1.20 (0.68-2.10)
VM 1.55 (0.88-2.73) 1.34 (0.71-2.52)
Journal of Hospital Medicine® Vol 15 | No 8 | August 2020
aOR, 3.14; 95% CI: 1.52-6.50

Sohil Khan et al. Expert Opinion on Pharmacotherapy. Published online: 04 Aug 2020. DOI:
10.1080/14656566.2020.1792884
Critical Care Medicine. DOI: 10.1097/CCM.0000000000004363
Parallel, double-blind, placebo-
controlled, randomized.
Manaus, Brazil. Patients were
randomly allocated (1:1 ratio) to
receive either intravenous MP (0.5
mg/kg) or placebo (saline
solution), twice daily, for 5 days. A
modified intention-to-treat (mITT)
analysis was conducted. The
primary outcome was 28-day
mortality.
with SpO2 ≤ 94% at room air OR in use of supplementary oxygen OR under IMV.
doi/10.1093/cid/ciaa1177/5891816 by guest on 14 August 2020

doi/10.1093/cid/ciaa1163/5890108
Multivariable linear regression analysis of characteristics associated with ventilator free days.
We identified 269 (49.1%) of 548 patients as severe cases on admission. The estimated mortality was 1.1% in non-severe
patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex,
older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use
were associated with death in patients with severe COVID-19.
American Academy of Allergy, Asthma & Immunology. https://doi.org/10.1016/j.jaci.2020.04.006

Pros: con dosis de ≤ 0.5 – 1 mg/ kg/día por hasta 7 días
Respiratory Physiology & Neurobiology 280 (2020) 103492

16 studies were finally included in meta-analysis. The study population ranged from 30 to 1099. The heterogeneity was
considerably high (i.e., I2, 88%; P = 0.00001), severe patients were found to be more likely to require corticosteroids therapy (RR =
2.11, 95%CI = 1.53–2.92, P = 0.00001). No statistically difference was found between survivors and non-survivors regarding the
use of corticosteroids (RR =1.38, 95%CI=0.87-2.18, P=.17)
Our brief meta-analysis indicates that patients in critical conditions are more likely to receive corticosteroids. Moreover, there are
no differences in mortality among COVID-19 pneumonia patients with or without corticosteroids treatment. More studies are
needed to elucidate how and when to use corticosteroids should be used in severe COVID-19 patients
American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.06.040

WHO reference number: WHO/2019-nCoV/Corticosteroids/2020.1
In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did
not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped
early and likely was underpowered to find a statistically and clinically important difference in the primary outcome .
JAMA. doi:10.1001/jama.2020.16761
A total of 299 patients (mean [SD] age, 61 [14] years; 37%women) were enrolled and all completed follow-up. Patients randomized to
the dexamethasone group had a mean 6.6 ventilator-free days (95%CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days
(95%CI, 2.9-5.4) in the standard care group (difference, 2.26; 95%CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group
had a mean SOFA score of 6.1 (95%CI, 5.5-6.7) vs 7.5 (95%CI, 6.9-8.1) in the standard care group (difference, −1.16; 95%CI, −1.94 to
−0.38;P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free
days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days.
JAMA. doi:10.1001/jama.2020.17021
JAMA. doi:10.1001/jama.2020.17023
Jeronimo CMP et al. Methylprednisolone as adjunctive therapy for patients hospitalized with COVID-19 (Metcovid): A randomised,
double-blind, Phase IIb, placebo-controlled trial. Clin Infect Dis 2020 Aug 12; [e-pub]. (https://doi.org/10.1093/cid/ciaa1177)
https://www.jwatch.org/na52352/2020/09/09/steroids-covid-19-debate-continues?query=C19&cid=DM98874_NEJM_Registered_Users_and_InActive&bid=262839716
Varón 62 años. Sin comorbilidades. Del día 2 de síntomas al día 7 de síntomas. Aumento de dísnea, fatiga, SatO2: 95%. FR: 21.
FC 86. Fiebre en disminución. PCR: Positivo. ¿Tratamiento?
Una historia que no se debe repetir:
La hidroxicloroquina (cloroquina)
Con o sin azitromicina
Hydroxychloroquine
• Inhibition of viral enzymes or processes such as viral DNA and
RNA polymerase, viral protein glycosylation, virus assembly,
new virus particle transport, and virus release.
• Other mechanisms may also involve ACE2 cellular receptor
inhibition, acidification at the surface of the cell membrane
inhibiting fusion of the virus, and immunomodulation of
cytokine release
Chloroquine
• Inhibition of viral enzymes or processes such as viral DNA and
RNA polymerase, viral protein glycosylation, virus assembly,
new virus particle transport, and virus release.
• Other mechanisms may also involve ACE2 cellular receptor
inhibition, acidification at the surface of the cell membrane
inhibiting fusion of the virus, and immunomodulation of
cytokine release.
Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label
non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI :
10.1016/j.ijantimicag.2020.105949
F.R. Rosendaal, Review of: “Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an
open-label non-randomized clinical trial Gautret et al 2010, DOI:10.1016/j.ijantimicag.2020.105949, International Journal
of Antimicrobial Agents, https://doi.org/10.1016/j.ijantimicag.2020.106063
Soto A. Acta Med Peru. 2020;37(3). doi: 10.35663/amp.2020.373.1548
French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to
emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day

Molina JM et al. No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of
Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection, M´edecine et Maladies
Infectieuses (2020), doi: https://doi.org/10.1016/j.medmal.2020.03.006
16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020.
medRxiv preprint doi:https://doi.org/10.1101/2020.04.10.20060558

IDSA Guidelines for Management of COVID-19 (2020)
April 29, 2020

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)
• Do not use chloroquine or hydroxychloroquine alone or in combination with

azithromycin as prophylaxis against COVID-19 due to known harms and no available
evidence of benefits in the general population.
• Do not use chloroquine or hydroxychloroquine alone or in combination with
azithromycin as a treatment of patients with COVID-19 due to known harms and no
available evidence of benefits in patients with COVID-19.
• In light of known harms and very uncertain evidence of benefit in patients with COVID-
19, using shared and informed decision making with patients (and their families),
clinicians may treat hospitalized COVID-19–positive patients with chloroquine or
hydroxychloroquine alone or in combination with azithromycin in the context of a
clinical trial
13 mayo 2020. https://doi.org/10.7326/M20-1998

Among patients hospitalized in metropolitan New York with COVID-19, treatment with
hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly
associated with differences in in-hospital mortality. However, the interpretation of these findings
may be limited by the observational design
May 11, 2020. JAMA. 2020;323(24):2493-2502. doi:10.1001/jama.2020.8630

31 May 2020. Journal of Neuroimmune Pharmacology. https://doi.org/10.1007/s11481-020-09930-x
The trial has proceeded at unprecedented speed, enrolling over 11,000 patients from 175 NHS hospitals
in the UK
The independent Data Monitoring Committee has reviewed the emerging data about every two weeks to
determine if there is evidence that would be strong enough to affect national and global treatment of
COVID-19
4 June 2020: We have concluded that there is no beneficial effect of hydroxychloroquine in patients
hospitalised with COVID-19. We have therefore decided to stop enrolling participants to the
hydroxychloroquine arm of the RECOVERY Trial with immediate effect. We are now releasing the
preliminary results as they have important implications for patient care and public health
Varón 50 años con covid-19
Disnea, fatiga, fibre
SatO2 97%
3 días de evolución
Hydroxychloroquine in Non hospitalized Adults With
Early COVID-19: A RCT
• Diseño: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020.
Internet-based trial across the United States and Canada (40 states and 3 provinces). Symptomatic,
nonhospitalized adults. laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4
days of symptom onset.
• Intervención: HCQ (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or
masked placebo.
• Outcome: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue
scale. The primary end point was change in overall symptom severity over 14 days.
Resultados
• Severidad al día 14: no diferencias
• Síntomas al día 14: no diferencias
• RAM: mayor en el grupo HCQ
• Hospitalizaciones: no diferencias
Caleb P. Skipperet al. Annals of internal medicine. https://doi.org/10.7326/M20-4207. publicado: 16 julio 2020
RIP: Hidroxicloroquina
• FDA: el 15 de junio retira la autorización de uso por emergencia a
la hidroxicloroquina
• NIH: el 20 de junio retira de su estudio a la hidroxicloroquina por

no encontrar beneficios (no daños tampoco)
• OMS: el 4 de julio retira se su estudio a la hidroxicloroquina por no

encontrar beneficios
• MINSA: amplía su uso a ambulatorios!!!!!
https://espanol.medscape.com/verarticulo/5905674?src=soc_fb_200717_mscpmrk_news_id_covid19&faf=1
Patients enrolled in the open label RECOVERY trial are
randomized to standard care or to one of six treatment
arms: hydroxychloroquine (now ended), dexamethasone
(also ended), lopinavir-ritonavir, azithromycin,
convalescent plasma, and, in a second randomisation
for patients who deteriorate, the anti-inflammatory
drug tocilizumab
BMJ 2020;370:m2670 http://dx.doi.org/10.1136/bmj.m2670. Published: 8 July 2020

Effect of Hydroxychloroquine in Hospitalized Patients 4 with COVID-19:
Preliminary results from a 5 multi-centre, randomized, controlled trial
RECOVERY Collaborative Group n=4716 pacientes. open-label

Effects of allocation to hydroxychloroquine on 28−day mortality
by baseline characteristics

Hydroxychloroquine for Early Treatment of Adults
with Mild Covid-19: A Randomized Controlled Trial
• Diseño: multicenter, open label, RCT in Catalonia (Spain). 17/03/2020 – 26/05/2020. non-hospitalized adult
patients. confirmed SARS-CoV-2 infection. less than five days of symptoms.
• Intervención: HCQ (800 mg on day 1, followed by 400 mg once daily for 6 days) or no antiviral treatment
(not-placebo controlled).
• Outcome: reduction of viral RNA load in NSF up to 7 days. disease progression. time to complete resolution
of symptoms. Adverse events were assessed up to 28 days.
Control HCQ
157 136
Carga viral día 3 No diferencias
Carga viral día 7 No diferencias
Riesgo Hospitalización No diferencias
Tiempo hasta resolución No diferencias
Clinical Infectious Diseases, ciaa1009, https://doi.org/10.1093/cid/ciaa1009. Published: 16 July 2020

We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized
patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a
maximum of 4 liters per minute of supplemental oxygen
This article was published on July 23, 2020. at NEJM.org. DOI: 10.1056/NEJMoa2019014
MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from
inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective,
including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-
19
We found 32 studies for a total 29,192 studied participants but only two studies at low risk of bias,
one on treatment and one on prophylaxis of COVID-19.
Available evidence from moderate risk of bias studies suggests that treatment with CQ/HCQ
confers no benefit in terms of mortality in hospitalized patients with COVID-19 compared to
standard care. Furthermore, higher dose regimens and combination therapy with macrolide may be
associated with harm.
Postexposure prophylaxis with CQ/HCQ may not reduce the rate of COVID-19 but the quality of the
evidence on this is low.
Journal of Critical Care 59 (2020) 176–190
La calidad de la evidencia es alta al provenir de varios ensayos clínicos con resultados consistentes. Así,
con este cuerpo de evidencia a la fecha disponible, el IETSI no recomienda el tratamiento ambulatorio
ni hospitalario con cloroquina o hidroxicloroquina en pacientes con COVID-19 en cualquier fase de la
enfermedad o como profilaxis considerando la falta de beneficios clínicos y el mayor riesgo de daños
que causan, reportados en ensayos clínicos y estudios observacionales
… “Our results suggest that chloroquine and hydroxychloroquine will exert no antiviral
activity in human lung tissue and will not be effective against COVID-19, in keeping
with the results of recent clinical trial”
Nature | www.nature.com
medRxiv preprint doi: https://doi.org/10.1101/2020.04.16.20065920.this version posted April 23, 2020.
2,541 patients. Multi-center retrospective observational study.
Setting: The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated
health system; March 10, 2020 to May 2, 2020 were included
International Journal of Infectious Diseases 97 (2020) 396–403

To be considered under chronic treatment with HCQ, cases had to be prescribed with at least 2 grams
of HCQ per month, on average
Results: Out of 26,815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ,
while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After
adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the
odds ratio of SARS-CoV-2 infection for chronic treatment with HCQ has been 0.51 (0.37-0.70).
Conclusions: Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-
2 infection.
Ferreira A (1), MD, PhD, Oliveira-e-Silva A (2), MD, Bettencourt

doi:10.1111/1756-185X.13842
A Randomized Trial of Hydroxychloroquine
as Postexposure Prophylaxis for Covid-19
Boulware y col. June 3, 2020. DOI: 10.1056/NEJMoa2016638

COVID-19 - Australian National COVID-19 Clinical Evidence
Taskforce
Augusto Di Castelnuovo, et al., European Journal of Internal Medicine, https://doi.org/10.1016/j.ejim.2020.08.019
Of 8075 patients with complete discharge data on 24th of May and diagnosed before the 1st of May, 4542
received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%)
and 957/3533 (27.1%), respectively
Compared to the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤ 5 days
(n=3975) and > 5 days (n=3487) after symptom onset (adjusted HR 0.701, 95% CI 0.617–0.796 and adjusted HR
0.647, 95% CI 0.525–0.797, respectively).
Lucy Catteau et al. International Journal of Antimicrobial Agents (2020), doi:https://doi.org/10.1016/j.ijantimicag.2020.106144

In patients with severe COVID-19, adding azithromycin to standard of care treatment (which
included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the
routine use of azithromycin in combination with hydroxychloroquine in patients with severe
COVID-19.
www.thelancet.com Published online September 4, 2020 https://doi.org/10.1016/S0140-6736(20)31862-6

Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19
94 patients but the combination of hydroxychloroquine and azithromycin significantly increased 95 mortality.
Fiolet T et al. Clinical Microbiology and Infection, https://doi.org/10.1016/j.cmi.2020.08.022.
As very low-quality evidence suggests an increased risk of mortality and adverse event with HCQ plus
Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this
combination for treatment of hospitalized adults with COVID-19 infection.
Das RR et al. Front. Med. 7:482. doi: 10.3389/fmed.2020.00482

Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-
cause mortality (OR:2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly
higher in patients on HCQ compared to patients on control agent
Ullah et al. J Clin Med Res. 2020;12(8):483-491. doi: https://doi.org/10.14740/jocmr4233
Considering previous studies and our findings, HCQ with or without AZM does not seem to be
effective in treating patients with severe COVID-19
DARU Journal of Pharmaceutical Sciences. https://doi.org/10.1007/s40199-020-00367-4

A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included.
A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality
rates, observational studies provided conflicting results. RCTs, including one large
British RCT that has not yet been published, showed no significant effect of HCQ on
mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure
prophylactic agent was found to be ineffective in one RCT.
Rakedzon et al. Rambam Maimonides Med J 2020;11 (3):e0025. Review . doi:10.5041/RMMJ.10416
HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population
European Journal of Clinical Pharmacology. https://doi.org/10.1007/s00228-020-02962-5

doi: 10.1002/jmv.26442.
Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects
outweigh its protective effect from radiological progression in non-severe COVID-19 patients. Benefit-
risk balance should guide hydroxychloroquine use in COVID-19
Dr. Topol Dr. Hahn
Sobre Hidroxicloroquina: Immediately after President Trump widely and aggressively promoted hydroxychloroquine as a "miracle
drug," on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug without any sufficient or meaningful
supportive evidence. Proof of that was borne out on June 15, 2020 when you revoked that EUA, acknowledging lack of efficacy
and "ongoing serious cardiac adverse events and other potential serious side effects.
Arunmozhimaran Elavarasi et al. J Gen Intern Med. DOI: 10.1007/s11606-020-06146-w. 3 sep 2020
La locura por la ivermectina
http://revistas.unheval.edu.pe/index.php/repis/article/view/747/6
33
New Series, Vol. 265, No. 5174 (Aug. 12, 1994), pp. 956-959
Although several clinical trials are now underway to test possible therapies, the worldwide
response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report
here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum
anti-viral activity in vitro, is an
inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post
infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin
therefore warrants further investigation for possible benefits in humans.
To test the antiviral activity of ivermectin towards SARS-CoV-2, we infected Vero/hSLAM cells with
SARS-CoV-2 isolate Australia/VIC01/2020 at an MOI of 0.1 for 2 h, followed by the addition of 5 μM
ivermectin.
Caly et al. https://doi.org/10.1016/j.antiviral.2020.104787. Antiviral Research 178 (2020) 104787

Nevertheless, the real question is, will it reach the stage of randomized clinical control trials in SARS-
CoV-2-infected patients, or will it fail in the in vivo study stage? Although no clinical trials have reported
its efficacy and safety in the context of COVID-19 yet, is expected to see in the near future them,
delivering information about its potential therapeutic action in the clinical setting.
Caly et al.1 reported that ivermectin inhibited severe acute respiratory syndrome-coronavirus
2 (SARS-CoV-2) in vitro for up to 48 hours using ivermectin at 5 μM.
The concentration resulting in 50% inhibition (IC50; 2 μM) was > 35× higher than the
maximum plasma concentration (Cmax) after oral administration of the approved dose of
ivermectin when given fasted
Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations
do not reach the IC50, even for a dose level 10× higher than the approved dose.
Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC50 in the lungs after
single oral administration of the approved dose (predicted lung: 0.0873 μM) or at doses 10×
higher that the approved dose administered orally (predicted lung: 0.820 μM)
Virginia D. Schmith. Received April 21, 2020; accepted May 6, 2020. doi:10.1002/cpt.1889
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The
FDA approved drug ivermectin inhibits the replication of
SARS-CoV-2 in vitro. Antiviral Res. 2020:104787.
https://doi.org/10.1016/j.antiviral.2020.104787.
Pecho et al. https://doi.org/10.35839/repis.4.3.747

The Journal of Antibiotics https://doi.org/10.1038/s41429-020-0336-z
Es el llamado Argumentum ad ignorantiam, que consiste en creer que «el desconocimiento de evidencias en
contra de la idea que apoyamos cuenta como una evidencia a su favor». Y nada más alejado de la realidad y,
además, con la capacidad de generar múltiples pruebas ensayo-error de consecuencias imprevisibles,
particularmente en una enfermedad de la que desgraciadamente conocemos todavía muy poco
la dosis de ivermectina utilizada in vitro es de 5 M. Para alcanzar esa concentración en el ser humano se
precisaría la administración oral del orden de 1.000-1.200 mg de ivermectina. Según la ficha técnica de este
fármaco, su dosis probada en humanos (voluntarios sanos) es en torno a 100-120 mg (dosis única) y los efectos
secundarios graves por intoxicación son ataxia y comicialidad3
López Reboiro ML, et al. COVID-19 y Argumentum ad ignorantiam o «no todo vale». Rev Clin Esp.
2020. https://doi.org/10.1016/j.rce.2020.04.013
La evidencia a la fecha en torno al uso de ivermectina en pacientes con COVID-19 proviene de estudios in
vitro y un único estudio observacional (Cepelowicz-Rajter et al. 2020), pues el estudio de Patel et al., ha sido
retirado por cuestionamientos serios a la integridad de la investigación, la que llevó a que las publicaciones
hechas con dicha información sean retractadas de revistas como el Lancet y el New England Journal of
Medicine.
Aunque el estudio observacional tiene resultados alentadores, no es posible atribuir dichos resultados a la
ivermectina dada la imposibilidad de los estudios observacionales de controlar por sesgos de selección, de
información y factores de confusión.
Así, la evidencia que apoya el uso de ivermectina en pacientes COVID-19 es preliminar y de muy baja
calidad, por lo que se requiere de los resultados de ECA para poder hacer recomendaciones clínicas a favor
de su uso, tal y como lo recomienda la FDA.
Ivermectina
• In vitro reduction of viral RNA in Vero-hSLAM cells 2 hours postinfection with
SARS-CoV-2 clinical isolate Australia/VIC01/2020.
• The authors note that this preliminary study does not translate to human use and
the effective dose is not established at this early stage of discovery.
• More research is needed to determine if an antiviral effect would be elicited in

humans, as the concentrations tested were much higher than what is achieved from
the normal oral dose
• Available pharmacokinetic data from clinically relevant and excessive dosing

studies indicate that the SARS-CoV-2 inhibitory concentrations for ivermectin are
not likely attainable in humans.
Sobre ivermectina
• Chaccour et al believe the recent findings regarding ivermectin warrant

rapid implementation of controlled clinical trials to assess efficacy against
COVID-19.
• They also raise concerns regarding ivermectin-associated neurotoxicity,

particularly in patients with a hyperinflammatory state possible with COVID-
19.
• Finally, evidence suggests that ivermectin plasma levels with meaningful

activity against COVID-19 would not be achieved without potentially toxic
increases in ivermectin doses in humans.
Univariate analysis showed lower mortality in the ivermectin
group (15·0% versus 25·2%, OR 0·52, CI 0·29-0·96, P=0·03).
Mortality was also lower among patients with severe pulmonary

involvement treated with ivermectin (38·8% vs 80·7%, OR 0·15,
CI 0·05-0·47, p=0·001)
There were no significant differences in successful extubation

rates (36·1% vs 15·4%, OR 3·11 (0·88-11·00), p=0·07) or
length of stay.
After multivariate adjustment for confounders and mortality

risks, the mortality difference remained significant (OR 0·27, CI
0·09-0·85, p=0·03)
194 patients were included in the propensity-matched cohort;

mortality was again significantly lower in the ivermectin group
(12.4% vs 25.8%, OR 0·41, CI 0·19-0·87, p=0·02).
hydroxychloroquine and hydroxychloroquine plus azithromycin were higher in the usual care group
This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3631261
El principal resultado de este estudio es que, en los 14 días luego de
enrolarse, 7.4% de los participantes que recibieron ivermectina
desarrollaron algún síntoma (fiebre, tos, dolor de garganta, mialgia,
diarrea, o falta de aire), en tanto que 58.4% de los pacientes del grupo
control desarrollaron alguno de esos síntomas.
Puesto que este estudio es de etiqueta abierta (todos los pacientes
sabían qué estaban recibiendo), y el desenlace es tan subjetivo
(ninguna prueba, solo síntomas), existe un GRAN riesgo de que el
efecto placebo y el sesgo de deseabilidad social (entre otros) expliquen
el supuesto beneficio encontrado.
https://www.facebook.com/evisalud
Azithromycin
• Macrolides may have immunomodulatory properties in pulmonary inflammatory
disorders.
• They may downregulate inflammatory responses and reduce the excessive cytokine
production associated with respiratory viral infections; however, their direct effects on
viral clearance are uncertain.
• Immunomodulatory mechanisms may include reducing chemotaxis of neutrophils

(PMNs) to the lungs by inhibiting cytokines (i.e., IL-8), inhibition of mucus
hypersecretion, decreased production of reactive oxygen species, accelerating
neutrophil apoptosis, and blocking the activation of nuclear transcription factors.
JAMA Network Open. 2020;3(6):e208199. doi:10.1001/jamanetworkopen.2020.8199
Smith D, et al. Thorax 2020;0:1–35. doi:10.1136/thoraxjnl-2019-213929
Drug Safety. https://doi.org/10.1007/s40264-020-00976-7
JAMA Published online July 30, 2020
A study that reviewed 133 individuals with Strongyloides hyperinfection found that hyperinfection was associated with
corticosteroid administration in 83%of cases, with an average dose of 40mg per day of prednisone.
Geri G, Rabbat A, Mayaux J, et al. Strongyloides stercoralis hyperinfection syndrome. Infection. 2015;43(6):691-698.
BMJ2020;370:m2980
http://dx.doi.org/10.1136
bmj.m2980
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
Available at https://www.covid19treatmentguidelines.nih.gov/.
Sohil Khan et al. Expert Opinion on Pharmacotherapy. Published
online: 04 Aug 2020. DOI:
10.1080/14656566.2020.1792884
• No uso de hidroxicloroquina (cloroquina) en covid-19
• No uso de hidroxicloroquina (cloroquina) con azitromicina en covid-19 hospitalizado
• Uso de los siguientes medicamentos sólo dentro de ensayos clínicos: tocilizumab, lopinavir/ritonavir, plasma, famotidina
• Comentario: sabemos que tocilizumab falló en demostrar cualquier beneficio frente a placebo, que lopinavir/ritonavir fue
retirado del Recovery y no se recomienda ya ni en ECAs, el plasma aún está en evaluación pero no es prometedor (ojalá salga
algo favorable). Probablemente veamos algunos resultados buenos con famotidina.
• En covid-19 severo (severo tiene hipoxemia) dosis bajas de corticoides o sus equivalentes
• Comentario: nunca ni idsa ni otras recomendaron "pulsos".
• En hospitalizados si hay hipoxemia pero no usa oxígeno: no corticoides

• Comentario: en leves y moderados no usar
• Remdesivir sólo en covid-19 severo en oxigenoterapia que no sea ECMO ni VM por 5 días
• Muy modesto beneficio para el costo
Archives of Virology. https://doi.org/10.1007/s00705-020-04693-5
Desai A, Kulkarni A, Rajkumar SV, Gyawali B, Clinical Trial Endpoints in Severe COVID-19, Mayo Clinic Proceedings (2020), doi:
https://doi.org/10.1016/j.mayocp.2020.05.025
https://saludconlupa.com/comprueba/cientificamente-comprobado-un-analisis-de-los-tratamientos-mas-usados-contra-el-covid-19/
Omeprazol, ranitidina, famotidina y Covid-19
• There is some biological plausibility to the association, as the paper
nicely describes. The authors note that PPIs may impair a primary line
of defense against infection by substantially raising gastric pH. And
SARS-CoV-2 can enter the body through enterocytes, which express
the angiotensin-converting enzyme 2 receptor required for the virus to
enter the cell.
• In a series of 205 patients with COVID-19, 29% had a positive result for
SARS-CoV-2 on fecal testing with reverse-transcriptase polymerase
chain reaction. Two patients had infectious SARS-CoV-2 cultured from
feces
• The odds ratios for COVID-19 associated with daily or twice-daily PPI
use vs no use were
• Dosis única: 2.15 y dosis dobles: 3.67, respectively
• In contrast, H2RAs were not associated with a higher risk for COVID-19.
Almario et al. preprint
878 SARS-CoV-2. Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020
The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as
combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed
propensity score matching to adjust for age differences between groups.
In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower
median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30
ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).
doi: 10.1053/j.gastro.2020.05.053
https://www.medscape.com/viewarticle/936306?src=soc_fb_200826_mscpedt_news_mdscp_famotidine&faf=1
Methods: A physician-sponsored cohort study of
cetirizine and famotidine was performed in
hospitalized patients with severe to critical
pulmonary symptoms. Pulmonologists led the
inpatient care in a single medical center of 110
high-acuity patients that were treated with
cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d.
plus standard of-care.
Results: Of all patients, including those with Do Not

Resuscitate directives, receiving the dual-histamine
receptor blockade for at least 48 h, the combination
drug treatment resulted in a 16.4% rate of
intubation, a 7.3% rate of intubation after a
minimum of 48 h of treatment, a 15.5% rate of
inpatient mortality, and 11.0 days duration of
hospitalization. The drug combination exhibited
beneficial reductions in inpatient mortality and
symptom progression when compared to published
reports of COVID-19 inpatients. Concomitant
medications were assessed, and
hydroxychloroquine was correlated with worse
outcomes.
Pulmonary Pharmacology & Therapeutics 63 (2020) 101942

https://www.news-medical.net/news/20200916/Azelastine-antihistamine-inhibits-SARS-CoV-2-infection-in-nasaltissue-in-vitro.aspx
10.21203/rs.3.rs-26247/v1. Preprint: Please note that this article has not completed peer review
In a retrospective cohort study of patients with COVID-19 from Shamir Medical Centre, Israel, we monitored any use
of ibuprofen from a week before diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality
and the need for respiratory support, including oxygen administration and mechanical ventilation.
In this cohort of COVID-19 patients, ibuprofen use was not associated with worse clinical outcomes, compared with
paracetamol or no antipyretic
E. Rinott, Clin Microbiol Infect 2020;26:1259.e5e1259.e7

https://www.healio.com/news/endocrinology/20200724/vitamin-d-deficiency-more-common-among-covid19-patients-admitted-to-icu
https://www.healio.com/news/endocrinology/20200911/low-vitamin-d-levels-independently-associated-with-severe-covid19-cases-
death?fbclid=IwAR3tYTtIM5pzeSXOLD5ez1FC_egOndnqQgjVFHXyyi7hDwp5HODfa3Omj0o
In this large observational population study, we show a
strong association between vitamin D deficiency and Covid-
19 occurrence. After adjustment for baseline characteristics
and prior vitamin D levels, acquisition of liquid vitamin D
formulations is associated with decreased risk for Covid-19
infection.

Mortality rates in metformin users compared with non-users among patients with type 2 diabetes
hospitalized for COVID-19 infection.
A.J. Scheen, Metformin and COVID-19: From cellular mechanisms to reduced mortality, Diabetes and Metabolism (2020),
https://doi.org/10.1016/j.diabet.2020.07.006
METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES
medRxiv preprint doi: https://doi.org/10.1101/2020.07.29.20164020.this version posted July 31, 2020
Retrospective electronic health record. 25,326 subjects tested for COVID-19. 2/25/20 - 6/22/20. University of Alabama.
Forest plot showing adjusted mortality risk in subjects with COVID-19 and T2D
• Diabetes was associated with a dramatic increase in mortality (OR 3.62; 95%CI 2.11-6.2; p<0.0001).
• Metformin treatment was independently associated with a significant reduction in mortality in subjects
with diabetes and COVID-19 (OR 0.33; 95%CI 0.13-0.84; p=0.0210).
Eligible patientswere randomized in a 1:1 ratio to receive either usual care alone or usual care plus rhG-CSF (GRAN;
Kyowa Hakko Kirin China Pharmaceutical Co Ltd; 5 μg/kg, subcutaneously once daily, from days 0 to 2
JAMA Intern Med. doi:10.1001/jamainternmed.2020.5503

Preprint: Please note that this article has not completed peer review
Twelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12
(92%), with a median time to discharge of 5 days

Bosteels et al. Trials (2020) 21:491

https://doi.org/10.1186/s13063-020-04451-7
Meta-analysis of Effect of Statins in Patients with COVID-19
Am J Cardiol 2020;00:1−3
Doi 10.5867/medwave.2020.06.7978
Downloaded from www.ccjm.org on September 16, 2020. Doi:10.3949/ccjm.87a.ccc046
The isolation and characterization of
an alpaca-derived single domain
antibody fragment, Ty1, that
specifically targets the receptor
binding domain (RBD) of the SARS-
CoV-2 spike, directly preventing ACE2
engagement. Ty1 binds the RBD with
high affinity, occluding ACE2
NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-18174-5

https://www.jwatch.org/fw117050/2020/09/19/latest-covid-19-news-week-ending-sept-19
Ciclesonide, suppressed human coronavirus replication in cultured cells, but did not suppress replication of
respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the
cause of COVID-19) replication (EC90) was 6.3 μM.
… These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a
candidate drug for treatment of patients suffering MERS or COVID-19
Matsuyama S, Kawase M, Nao N, Shirato K, Ujike M, Kamitani W, Shimojima M, Fukushi. The inhaled
corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15. bioRxiv 2020:
2020.2003.2011.987016
No evidencia sólida al momento a
favor de su uso de:
• Vitaminas y oligoelementos
• Doxiciclina
• Ozono: solo o en combinación
• Bromhexidina
• Acetilcisteína
• Antibióticos
• Heparina nebulizada
• Famotidina
• Ibuprofeno (oral, ¿nebulizado?)
• Estatinas (no suspender en usuarios crónicos, 30% menos mortalidad)
• Óxido Nítrico
• Litio
• Corticoides inhalados
• Broncodilatadores
Conclusiones
• No se recomienda usar: lopinavir/ritonavir, tocilizumab,
hidroxiclorquina, cloroquina, azitromicina, ivermectina, plasma
convaleciente, favipiravir/avifavir y otros como profilaxis primaria,
secundaria o tratamiento
• Recomendamos no usar Remdesivir
• No se recomienda usar omeprazol ni ranitidina:

• Famotidina: pero no como tratamiento de covid-19 (¿cetirizina?)
Tratamiento
• Leves y moderados: aislamiento, reposo relativo, mantener
movilización, alimentación, hidratación y sintomáticos condicionales
• Severos: oxígeno, corticoides (luego de 7 días de síntomas y a dosis de

6 mg al día de dexamentasona por 7 a 10 días, un ciclo, con
suspensión brusca, no pulsos, sólo en usuarios de oxígeno o VM), tal
vez Remdesivir, anticoagulación, ATB sólo si hay infección bacteriana
• Críticos: VMI protectiva y manejo de complicaciones

Programa

Varón 45 años, 5 días de fiebre. Dísnea. Saturación 91%. IgM: negativo. Tratamiento
DOI 10.15252/emmm.202012560 | EMBO Mol Med (2020) 12: e12560 | Published online 15 June 2020
the true
prevalence of
bacterial and
fungal
superinfections in
critically ill
COVID-19
patients
still remains
elusive
Intensive Care Med

https://doi.org/10.1007/s00134-020-06219-8
The overall proportion of COVID-19 patients with bacterial infection was 7.1% (95%CI 4.6 to 9.6%)
Bacterial infection was more common in critically ill patients 8.1% (95%CI 2.3 to 13.8)
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.
Thirty studies including 3834 patient. 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n = 2183, I 2 = 92
·2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I 2 = 74
·7% versus 4%, 95% CI 1-9, I 2 = 91 ·7%). The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n = 1014, I 2 = 62 ·3%), with
Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections.
L. Lansbury, B. Lim and V. Baskaran et al. / Journal of Infection 81 (2020) 266–275

JAMA. doi:10.1001/jama.2020.6775. Published online April 22, 2020.
https://doi.org/10.1016/j.chest.2020.07.089
Fan G, Tu C, Zhou F, et al. Eur Respir J 2020; 56: 2002113 [https://doi.org/10.1183/13993003.02113-2020].
A-DROP
Expanded A-DROP Score: A New Scoring System for the
Prediction of Mortality in Hospitalized Patients with Community-
acquired Pneumonia
The AUC of this score for the
prediction of 28-day mortality was
0.834 (95% CI: 0.794–0.874)
SCIEntIfIC REPOrTS | (2018) 8:14588 | DOI:10.1038/s41598-018-32750-2

DOI: 10.2169/internalmedicine.45.1691
Pathogenic species in sputum specimens which were collected from 10 to 25 days of onset of symptoms in 32
patients
Five cases: respiratory syncytial virus (RSV), human parainfluenza virus (HPIV), human metapneumovirus
(hMPV), rhinoviruso (rRhV) and enterovirus (EV) we found two interesting cases of coinfection with CoV-HKU1
Ten patients (31%): gram-negative bacteria Staphylococcus epidermidis and Acinetobacter baumannii. Candida
albicans
Zaragoza et al. Critical Care (2020)
24:383
https://doi.org/10.1186/s13054-020-
03091-2
Zaragoza et al. Critical Care (2020)
24:383
https://doi.org/10.1186/s13054-020-
03091-2
George PM et al. Thorax Epub ahead of print:[06/09/2020]. doi:10.1136/thoraxjnl-2020-215314
George PM et al. Thorax Epub ahead of print:[06/09/2020]. doi:10.1136/thoraxjnl-2020-215314
Anticoagulación
TEP no Covid-19
• Estados Unidos: 1/1000 personas/año ó 112 / 100 000
• El incremento en el uso de TC ha incrementado la detección
• De 1979-1998: disminución de la mortalidad de 191/1 000 000 habitants a 94/1 000 000
• 60-70% de pacientes con TVP presentan EP: la mitad asintomáticos
• El TEP es la tercera causa más común de muerte entre pacientes hospitalizados: 650,000 casos /
año
• 60% de pacientes que fallecieron durante hospitalización: TEP en autopsias
• 70% de ellos no se hizo el diagnóstico
• 10-15% de pacientes en cama en 1 semana presentan TVP

• 29-33% de todos los pacientes en la UCI: TVP
• 20-26% de todos los pacientes con enfermedad pulmonar que pasaron 3 ó más días en cama: TVP
• 27-33% de pacientes admitidos a UCI por IMA: TVP
• 48% de pacientes asintomáticos luego de un Bypass AoCo: TVP
https://emedicine.medscape.com/article/300901-overview
BMJ 2020;370:m2177 http://dx.doi.org/10.1136/bmj.m2177
Sakr et al. Ann. Intensive Care (2020) 10:124
https://doi.org/10.1186/s13613-020-00741-0
DOI: 10.1177/1076029620936350
Journal of Thrombosis and Thrombolysis (2020) 50:72–81
https://doi.org/10.1007/s11239-020-02138-z
Journal of Thrombosis and Thrombolysis (2020) 50:72–8. https://doi.org/10.1007/s11239-020-02138-z
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 8 AUGUST 2020
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 87 • NUMBER 8 AUGUST 2020
Retrospective cohort
study from April 1 -
April 25, 2020. The
date of final follow
up was June 12,
2020.

In patients who required mechanical ventilation (n = 395), in-hospital mortality was 29.1% with a median survival of 21 days for those treated with AC as
compared to 62.7% with a median survival of 9 days in patients who did not receive treatment dose AC. In a multivariate proportional hazards model, longer
duration of AC treatment was associated with a reduced risk of mortality (adjusted HR of 0.86 per day; 95% confidence interval: 0.82 to 0.89; p < 0.001).
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

DOI: 10.1177/1076029620936350
Liao et al. Critical Care (2020) 24:464
• Among 1981 potentially related studies, 49 articles (52 studies) comprising 20,523 COVID-19 patients
were enrolled in this meta-analysis
• The pooled prevalence of PE in COVID-19 patients was 8% (95% CI 6–11%; χ2 = 1259.68, P < 0.01;I2 =
95.95%; random-effects model)
• The pooled prevalence of PE in patients undergoing PE diagnosis was 28% (95% CI 22–34%; χ2 =
429.11,P < 0.01; I2 = 93.71%; random-effects model) based on 28 studies consisting of 4387 patients
undergoing PE diagnosis.
• The significantly higher pooled prevalence of PE was observed in COVID-19 patients admitted to ICU
(19%, 95% CI 14–25%; χ2 = 346.07, P < 0.01;I2 = 92.49%) compared with those admitted to non-ICU (9%,
95% CI 6–13%; χ2 = 379.37, P < 0.01; I2 = 94.99%).
Intensive Care Med
https://doi.org/10.1007/s00134-020-06235-8
País/estancia Incidencia TEP (%) Presencia en TAC
Francia No hospitalizados 1.1
Francia Hospitalizados 3.4 23 – 30
Hospitalizados 1.9 – 8.9
UCI 26.6
Francia / UCI 16.7 con profilaxis (SDRA)
Países Bajos / UCI 13.6 hasta 33.3 en el
seguimiento
Francia / UCI 20.6 en el seguimiento
Sakr et al. Ann. Intensive Care (2020) 10:124

https://doi.org/10.1186/s13613-020-00741-0
DOI: 10.1177/1076029620936350
72/328 (22%, 95%CI 18-27%) were found to have a PE
Neo Poyiadji. Radiology
Zavala-Flores et al. Acta Med Peru. 2020;37(3). doi:10.35663/amp.2020.373.1277
Programa

 Terapia con Oxigeno: dispositivos de administración y pronación
despierto
El cálculo de la estimación de la SAO responde a
la siguiente ecuación:
SAO = 103,3 – (altitud× 0,0047) + (Z)
siendo Z = 0,7 en hombres y 1,4 en mujeres.
Pulsioxímetro Choice MMed Fingertip MD300C2
Lorente-Aznar T, et al. Estimación de la saturación arterial de oxígeno en función de la altitud. Med Clin
(Barc). 2016. http://dx.doi.org/10.1016/j.medcli.2016.07.025
© 2020 by the Society for Academic Emergency Medicine
doi: 10.1111/acem.14053
Archivo Personal
Samuel Pecho
Dhont et al. Respiratory Research (2020) 21:198
https://doi.org/10.1186/s12931-020-01462-5
JAMA. 2020;324(1):57-67. doi:10.1001/jama.2020.9524. Published online June 4, 2020.
Con flujos entre 35 y 60 LPM se logran generar presiones faríngeas entre 5 – 7 cmH2O con boca
cerrada. Esta presión puede disminuir con boca abierta. Diversos estudios han demostrado que la
CNAF podría aumentar la capacidad residual funcional, mejorando así la distensibilidad pulmonar y
la oxigenación
Can J Anesth/J Can Anesth
https://doi.org/10.1007/s12630-020-01740-2
Vianello A et al. Thorax. doi:10.1136/
thoraxjnl-2020-214993
Respiration. DOI: 10.1159/000509104
High Flow Nasal Canula in Critically Ill
Severe COVID-19 Patients
146 versus 233: Requiring invasive mechanical ventilation at day 28 was 56% (95% confidence interval [CI], 47-64)
vs. 75% (95%CI 70-81), P (Gray test) <0.0001. Mortality at day 28 was 21% in the HFNC group vs. 30% in those
who did not receive HFNC, hazard ratio (HR) 0.69 (95%CI 0.45-1.07).
AJRCCM Articles in Press. Published August 06, 2020 as 10.1164/rccm.202005-2007LE
COVID-19 - Australian National COVID-19 Clinical
Evidence Taskforce
CPAP Artesanal
Samuel Pecho
2007
Oxigen therapy for acutely ill medical patients: a clinical practice guideline, BMJ 2018; 363: k4169
Derek K. Chu et al, Mortality and morbidity in acutelly ill adults treated with liberal versus conservative oxygen
therapy (IOTA): A systematic review and meta analysis, Lancet 2018, 391:1693-705
Alison E. Thompson. JAMA Internal Medicine Published online June 17, 2020
Daniel et al.; JAMMR, 32(12): 5-14, 2020; Article no.JAMMR.59101
Shang et al. Ann. Intensive Care (2020) 10:73
https://doi.org/10.1186/s13613-020-00689-1
Early conscious prone positioning in patients with COVID-19
Cohort of 24 patients with acute hypoxaemic respiratory failure due to receiving continuous positive airway pressure: a retrospective analysis
COVID-19 who required support with (CPAP).
The mean duration of PP in the first 24 hours was 8±5 hours. Few complications were observed and PP was continued for
a mean of 10±5 days
Winearls S, et al. BMJ Open Resp Res 2020;7:e000711. doi:10.1136/bmjresp-2020-000711
In patients without immediate need for
intubation, we can use prediction tools such as
the ROX index. ROX index was published by
Oriol Roca et al in 2016, it can predict the
failure to the use of HFNC in patients with
pneumonia. This index has not been validated
in COVID-19. However, in the original study a
small proportion of patients had viral
pneumonia

• Over the whole set of 2700 selected subjects, several demographic and health
parameters were associated with higher risk for respiratory support requirement
with the following odds ratios (OR) and 95% confidence intervals (95% CI):
– body mass index (BMI) in m/kg2 1.05 per unit increase (95% CI [1.03 ;1.08], p<0.0005)
– older age OR 1.02, 95%CI: [1.01 ; 1.03], p=0.003)
– chronic lung disease (OR 2.72, 95%CI: [1.90 ; 3.90], p<0.0005)
– frailty as assessed by PRISMA7 questionnaire (9)(OR 5.98, 95%CI: [2.96 ; 12.10], 5 p<0.0005)
– suggestive association with male sex (OR 1.49, 95%CI: [1.04 ; 2.13], p=0.029)
Respiration. DOI: 10.1159/000509104
On the basis of standard-
of-care (3), patients in
treatment group inhaled
H2-O2 (66% hydrogen;
33% oxygen) at 6 L/min
via nasal cannula by using
the Hydrogen/
Oxygen Generator
J Thorac Dis 2020;12(6):3448-3452 | http://dx.doi.org/10.21037/jtd-2020-057

Varón 18 años. Sin antecedentes. Contacto de un caso COVID-19
positivo. En el estudio de contactos al paciente PCR: positivo y TAC con
lesiones. Paciente asintomático. Saturación 95%
SatO2 con MR 15 lt: 91%
PaO2/FiO2: 180
• 10 días desde el inicio de síntomas

• Varón 72 años sin comorbilidades
• PCR: positivo bajo
• PCT: positivo bajo
• Dímero D: positivo bajo
SatO2 con MR 15 lt: 85%
PaO2/FiO2: 150
• 15 días desde el inicio de síntomas

• Varón 52 años HTA, DM. Estuvo en casa con 2 litros por concentrado
con SatO2 90%. Deterioro súbito
• PCR: positivo Alto
• PCT: positivo Alto
• Dímero D: positivo Alto
Programa

Rev Bras Ter Intensiva. 2020;32(2):166-196 Papazian et al. Ann. Intensive Care (2019) 9:69
Griffiths et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Resp Res 2019;6:e000420.
doi:10.1136/bmjresp-2019-000420
Type L, characterized by Low elastance (i.e., high compliance), Low ventilation to perfusion ratio, Low
lung weight and Low recruitability
Type H, characterized by High elastance, High right-to-left shunt, High lung weight and High
recruitability
AJRCCM Articles in Press. Published June 24, 2020 as 10.1164/rccm.202004-1293LE

Pickkers P. et al. COVID-19: 10 things I wished I’d known some months ago. Intensive Care Medicine (2020)
Intensive Care Med (2020) 46:579–582
https://doi.org/10.1007/s00134-020-
Published Online March 20, 2020 https://doi.org/10.1016/ S2213-2600(20)30127-2
www.thelancet.com/respiratory Published online April 6, 2020 https://doi.org/10.1016/S2213-2600(20)30161-2
Papazian et al. Ann. Intensive Care (2019) 9:69
This article was published on May 15,
2020, at NEJM.org.
DOI: 10.1056/NEJMcp2009575
Copyright © 2020 Massachusetts Medical Society
www.ccmjournal.org June 2020 • Volume 48 • Number 6
Square root SpO2/FiO2 and mortality risk was
demonstrated, with a unit decrease in the marker
corresponding to 1.82-fold increase in mortality risk
(95% CI: 1.56–2.13).
Lu et al. Respiratory Research (2020) 21:194. https://doi.org/10.1186/s12931-020-01455-4

COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National
Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/.
Varón 56 años. HTA. Asma. Deterioro progresivo de la
función respiratoria en 3 días. SatO2: 88% con CBN 5
Estuvo en casa usando oxígeno por Balón
Una vez se haya alcanzado la estabilidad clínica, los pacientes con alto riesgo de desarrollar debilidad adquirida en la
UCI deberán ser canalizados a fisioterapia para el inicio de un protocolo de movilidad oportuna. Se recomienda que
se prescriban ejercicios de baja intensidad, utilizando equipos preferentemente individuales (desechable) para cada
paciente (por ejemplo, bandas de resistencia elástica). En caso de requerir equipo adicional, como cicloergómetro o
tablas de verticalización, se deben tener las precauciones necesarias, como es la desinfección meticulosa, a fin de
evitar infecciones cruzadas, motivo por el cual se aconseja evitarlo, a menos que el uso de este equipo sea
expresamente necesario para la progresión de la movilización.
Acta Médica Grupo Ángeles. 2020; 18 (3): 333-335

• 108 patients were enrolled.
• Probable CAPA was diagnosed in 30 (27.7%) of patients after a median of 4 (2-8) days from (ICU) admission
• Kaplan-Meier curves showed a significant higher 30-day mortality rate from ICU admission among patients with
either CAPA (44% vs 19%, p= 0.002) or PIPA (74% vs 26%, p<0.001) when compared with patients not fulfilling
criteria for aspergillosis.
• The association between CAPA [OR 3.53 (95%CI 1.29-9.67), P=0.014] or PIPA [OR 11.60 (95%CI 3.24-41.29)
p<0.001] with 30-day mortality from ICU admission was confirmed even after adjustment for confounders with
a logistic regression model.
• Among patients with CAPA receiving voriconazole treatment (13 patients, 43%) A trend toward lower mortality
(46% vs 59% p=0.30) and reduction of galactomannan index in consecutive samples was observed.
CAPA definition consisting in COVID-19 positive patients admitted to the ICU with pulmonary infiltrates (entry
criterion) who had at least one of the following: serum GM index >0.5 or BAL GM index >1.0 or positive Aspergillus
BAL culture or cavitating infiltrate (not attributed to another cause) in the area of the pulmonary infiltrate[
Oxford University Press for the Infectious Diseases Society of America. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1065/5876990
Programa

 Manejo Paliativo, Post-Covid, complicaciones y secuelas por
COVID-19
https://www.medscape.com/viewarticle/937263?src=soc_fb_200914_mscpedt_news_mdscp_lungs&faf=1
Researchers at North Bristol NHS Trust found that 81 out of 110 discharged patients were still experiencing
symptoms such as breathlessness, excessive fatigue and muscle aches when invited back to clinic.
https://www.nbt.nhs.uk/news-media/latest-news/southmead-hospital-publishes-pioneering-research-long-term-effects
Complicaciones
• Las principales complicaciones son del aparato respiratorio
• Luego las neurológicas: delirio o encefalopatía, accidente cerebrovascular,

meningoencefalitis, alteración de los sentidos del olfato (anosmia) y el gusto
(disgeusia), ansiedad, depresión y problemas del sueño.
• En muchos casos las manifestaciones neurológicas se han reportado incluso en

ausencia de síntomas respiratorios. También hay reportes de casos de síndrome de
Guillain Barré en pacientes con COVID-19
morphine (median dose 10mg/24h subcutaneously
fentanyl (median dose 100 microgram/24h)
alfentanil (median dose 500 microgram/24h
Janssen DJA et al. COVID-19: Guidance on Palliative care from a European Respiratory Society International Task Force. Eur Respir J
2020; in press (https://doi.org/10.1183/13993003.02583-2020).
Janssen et al. COVID-19: guidance on palliative care from a European Respiratory Society international task force. Eur Respir J 2020; 56: 2002583
[https://doi.org/10.1183/13993003.02583-2020].
Management of post-acute covid-19 in primary care
• Management of covid-19 after the first three weeks is currently based on limited
evidence
• Approximately 10% of people experience prolonged illness after covid-19
• Many such patients recover spontaneously (if slowly) with holistic support, rest,
symptomatic treatment, and gradual increase in activity
• Home pulse oximetry can be helpful in monitoring breathlessness
• Indications for specialist assessment include clinical concern along with respiratory,
cardiac, or neurological symptoms that are new, persistent, or progressive
the bmj | BMJ 2020;370:m3026 | doi: 10.1136/bmj.m3026

• fatigue (53.1%)
• Dyspnea (43.4%)
• joint pain (27.3%)
• chest pain (21.7%)
87.4% reported persistence of at least 1

symptom, particularly fatigue and dyspnea
Published Online: July 9, 2020. doi:10.1001/jama.2020.12603

Goërtz YMJ, Van Herck M, Delbressine JM, et al. ERJ Open Res 2020; in press https://doi.org/10.1183/23120541.00542-2020
Readmisiones
• Among 292 respondents:
• 94% (274) reported experiencing one or more symptoms at the time of testing
• 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the
interview (median = 16 days from testing date),
• 26% among those aged 18–34 years
• 32% among those aged 35–49 years
• 47% among those aged ≥50 years.
• Among respondents reporting cough (43%), fatigue (35%), or shortness of breath (29%) at the time of testing,
continued to experience these symptoms at the time of the interview.
• These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient
illness, including young adults.
MMWR / July 31, 2020 / Vol. 69 / No. 30 US Department of Health and Human Services/Centers for Disease Control and Prevention
• Of 2864 discharged patients: 103 (3.6%) returned for emergency care after a median of 4.5 days, with 56
requiring inpatient readmission.
• The most common reason for return was respiratory distress (50%).
• Compared with patients who did not return, there were higher proportions of COPD (6.8%vs 2.9%) and
hypertension (36% vs 22.1%) among those who returned.
• Patients who returned also had a shorter median length of stay (LOS) during index hospitalization (4.5 [2.9,9.1]
vs 6.7 [3.5, 11.5] days; P adjusted = 0.006), and were less likely to have required intensive care on index
hospitalization (5.8% vs 19%; P adjusted = 0.001).
• A trend towards association between absence of in-hospital treatment-dose anticoagulation on index admission
and return to hospital was also observed (20.9% vs 30.9%, P adjusted = 0.06).
• On readmission, rates of intensive care and death were 5.8% and 3.6%, respectively.
J Gen Intern Med. DOI: 10.1007/s11606-020-06120-6. © Society of General Internal Medicine 2020
Varón 53 Años con Peso 94 Kilos y talla 1.75. sin antecedentes. Covid-
19 severo. 32 días en hospitalización, requirió apoyo de VMNI y VMI.
Hace 2 semanas salió de alta del hospital
Casos Clínicos
• Mujer 30 años, antecedentes de “bronquios” y uso de nebulización e
inhaladores cuando tenía crisis. Hasta 3 veces por año acudía a
emergencia. No recibe medicación entre crisis. Es obesa y siente que
le silba el Pecho
• Hace 2 semanas presentó 5 días de opresión en el pecho y PCR (-) en

HNF. Hoy Prueba Serológica IgG e IgM positivas. Al momento siente
que le silba el pecho
Mujer 60 años. Con Dolor dorsal a predominio derecho tipo punzante intermitente de
intensidad de 4 a 6/10 que disminuye con el uso de paracetamol 1g. Hace ejercicios
respiratorios Inter diario.
• Inició el 26 de Julio con abundante Rinorrea y tomó una pastilla de cetirizina al día por 9 días
• 1 de Agosto comenzó el dolor de espalda y tomó paracetamol
• 1° Prueba rápida del sábado 1 de agosto: Negativo
• 2° Prueba rápida: Viernes 7 de Agosto: IgM positivo en el Hospital en donde trabaja
• Al momento no síntomas
• Mujer de 61 años, en el día 15 de la enfermedad, evolución
favorable, una tac de ayer muestra:
Varón de 71 años
Regularmente jugaba tenis
5 días de leve dolor en tórax
No fiebre
SatO2 en reposo 92%
Un episodio de diarrea y actualmente no
percibe olores fuertes
Varón 59 con covid-19 en el día 7 de síntomas y 4to día de tratamiento:
recibe dexametasona 8 mg y ceftriaxona 2 g. Saturación 91-93% sin
oxígeno suplementario.
• Tos y baja de peso desde mayo 2020
• Prueba serológica negativa en mayo al

inicio de síntomas
• Recibió dexametasona y levofloxacino

SatO2 con CNAF 80
litros/90%: 92% con
PaO2/FiO2: 106
Rox: 3 a las 2 horas

PaO2/FíO2: 210
Mujer 48 años
Asma parcialmente controlada
9 días desde el inicio de síntomas
Curso desfavorable
PCR, PCT, Dímero D: elevados altos
Conclusiones
• El mejor tratamiento hasta el momento sigue siendo la prevención y
educación
• Hasta el momento no existe una medicación efectiva que sirva como
profilaxis pre o post exposición o como tratamiento en casos leves,
moderados, severos y críticos
• La mejor intervención que se puede ofrecer es oxigenoterapia en presencia
de saturación ≤ 92-93% a nivel del mar (en grandes alturas comparar con
familiares sanos)
• Sólo en casos críticos en VM o en oxigenoterapia la dexametasona a bajas
dosis puede reducir mortalidad (podría ser controversial) si se aplica luego
de 7 días de síntomas.
samuelpechosilva@gmail.com
Grupo Peruano de Salud Respiratoria
Muchas Gracias
https://bestpractice.bmj.com/topics/en-gb/3000168/treatment-algorithm#patientGroup-0-0
EviSalud – Evidencias en Salud
• 𝐂𝐮𝐫𝐬𝐨 "𝐏𝐮𝐛𝐥𝐢𝐜𝐚𝐧𝐝𝐨 𝐞𝐧 𝐫𝐞𝐯𝐢𝐬𝐭𝐚𝐬 𝐈𝐧𝐝𝐢𝐳𝐚𝐝𝐚𝐬" 📖
• Este curso online 💻, organizado por la UCSUR y dictado mayormente por Percy Mayta, es
imperdible para quienes queiran redactar y publicar artículos científicos. 👩‍🔬👨‍🔬
• 𝐋𝐢𝐧𝐤𝐬 𝐚 𝐥𝐚𝐬 𝐜𝐥𝐚𝐬𝐞𝐬:
• 👉 1) Publicación científica en Perú y búsqueda: https://bit.ly/3iYtX0o
• 👉 2) Autoría, filiación y creación de perfiles científicos: https://bit.ly/32b9f6q
• 👉 3) Elegir en qué revista publicar: https://bit.ly/3hgtzd3
• 👉 4) Escribir sin plagio: https://bit.ly/2Q5CvWK
• 👉 5) Escribir una carta al editor: https://bit.ly/2QcHRPS
• 👉 6) Escribir reportes de caso y artículos originales: https://bit.ly/33uqT5O
• 👉 7) Escribir resultados y métodos: https://bit.ly/3hItP3P
• 👉 8) Escribir discusión e introducción: https://bit.ly/3iHiWRa
• 👉 9) Titulación por publicación y docencia en investigación: https://bit.ly/35KJBJ9
• Resultados: No se identificó ningún estudio publicado ni en proceso de publicación que haya evaluado el
uso del dióxido de cloro o derivados del cloro, administrado por vía inhalatoria, oral o parenteral en
humanos, como agente preventivo o terapéutico de la COVID-19 o en infecciones por otros coronavirus.
Solo se identificó el registro de un único estudio catalogado como observacional que hasta ahora no tiene
resultados.
• Conclusiones: A la fecha, no existe evidencia científica que apoye el uso del dióxido de cloro o derivados
del cloro para prevenir o tratar la COVID-19.
Burela A et al. Dióxido de cloro y derivados del cloro para prevenir o tratar la COVID-19: revisión sistemática. Rev Peru Med Exp Salud Publica.
2020;37(4).doi: https://doi.org/10.17843/rpmesp.2020.374.6330.
Tema Adicional: Vacunas
Vacunas
• Tipos: proteínas virales, virus inactivados o virus atenuados, de ARN
• Vacunas de ARN
• Se inyecta ARN, las células lo absorben y producen la proteína por sí mismas. La vacuna se
produce “dentro de tu cuerpo.”
• Las ventajas del enfoque de ARN son claras: escalabilidad rápida. Puede producir ARN por
volumen y no necesita biorreactores complicados para hacerlo.
• ¿La desventaja de las vacunas de ARN? Todavía no sabemos mucho sobre ellos. Los datos
preliminares sugieren buenas respuestas de anticuerpos; eso es una ventaja, pero ¿cuáles
podrían ser los efectos secundarios? Se han planteado preocupaciones sobre la generación
de autoinmunidad (después de todo, son las propias células las que producen esas proteínas
virales), pero no se ha visto datos convincentes que muestren un alto riesgo aquí.
Vacuna de ARNm de Pfizer
• Codifica el dominio de unión al receptor del SARS-CoV-2, aunque con
algunas modificaciones para hacerlo un poco más inmunogénico.
• Necesitará dos dosis.
• Se suponía que el Ensayo de Pfizer reclutaría a 30.000 personas;
aparentemente alcanzaron ese objetivo la semana pasada. Se han
expandido a 44.000 personas para aumentar la diversidad.
• El director ejecutivo dice que tendrán datos de eficacia en octubre 2020,
pero los datos de seguridad tardan más y recuerden que necesita ambos
para la aprobación (al menos, si la FDA funciona).
• ClinicalTrials.gov enumera la fecha de finalización del estudio en abril de
2021.
Vacuna de ARNm de Moderna
• Codifica la proteína de pico, spike o espiga
• Aparte de eso, es bastante similar al enfoque de Pfizer, con dos dosis
estándar.
• Moderna se encuentra en a la mitad de un ensayo clínico de 30.000
pacientes.
Saved from URL: https://www.news-medical.net/news/20200911/Effective-simple-safe-self-amplifying-RNA-vaccines.aspx
Vacunas inactivadas
• Dificultad de fabricarlas a una escala verdaderamente global.

• Sinovac y Sinopharm, ambas en China, tienen estas vacunas en
ensayos clínicos activos
• El ensayo Sinovac: Fase 3 dirigido a una población de alto riesgo: 8870
trabajadores de la salud. Dada la mayor tasa anticipada de COVID-19
en esta multitud, ese es un enfoque inteligente, ya que les permite
hacer un estudio más pequeño con la potencia adecuada, lo que
podría ser una ventaja decente. Sin embargo, los datos sobre el
reclutamiento son difíciles de conseguir.
• La vacuna Sinopharm ya ha sido aprobada para su uso por el ejército
chino y, según informes de prensa, ha completado un ensayo clínico
con 50.000 personas en Oriente Medio. Falta más información sobre
ellas
Vacunas de vectores de adenovirus
• Las vacunas vectoriales utilizan un virus existente, modificado para

expresar una proteína SARS-CoV-2 como un caballo de Troya, para
acelerar la respuesta inmune.
• El vehículo es un virus vivo atenuado; podría generar una respuesta
inmunitaria más robusta. Pero esa es la desventaja también: Si tienes
anticuerpos contra el adenovirus de la vacuna, es posible que se
descomponga antes de que la nueva proteína tenga la oportunidad de
generar su propia respuesta de anticuerpos.
Vacunas de Vectores
• Tenemos tres vacunas de vectores en ensayos de fase 3
• CanSinoBio: empresa china, está utilizando el vector adenovirus 5 para introducir

proteína de pico. El adenovirus 5 es el caballo de batalla de la tecnología basada en
vectores. Pero hay un problema: muchos de nosotros ya lo hemos tenido. Un estudio
de 2004 encontró que el 37% de las personas en los Estados Unidos tienen
anticuerpos neutralizantes del adenovirus 5.
• AstraZeneca está utilizando un adenovirus de chimpancé como vector. Eso debería
ayudar a evitar el problema de que "ya es inmune". Eran hasta 20.000 de su objetivo
de 30.000 pacientes para el ensayo cuando, como se publicitó ampliamente, un caso
de mielitis transversa hizo que el estudio se detuviera. Desde entonces se ha
reiniciado. Podría existir una proteína en ese adenovirus de chimpancé que podría
provocar reactividad cruzada con alguna proteína humana: no sabemos.
• Gamaleya: Rusa.
• Están usando una combinación de adenovirus 5 y 26, pero por lo demás

tienen un enfoque similar.
• Rusia aprobó el uso de esta vacuna antes de que se completara el estudio de
fase 3.
• Al 4 de septiembre, solo se habían reclutado 3000 de las 40 000 personas
objetivo en su estudio de fase 3.
• Las preocupaciones sobre la calidad de los datos de su estudio de fase 1/2,
publicado en The Lancet, pueden moderar el entusiasmo por esta vacuna en
particular.
Conclusiones sobre las Vacunas
• Los datos preliminares sobre los títulos de anticuerpos son bastante similares para todas estas
vacunas (suponiendo que se pueda confiar en los datos, Rusia).
• Primero, es probable que la FDA considere una autorización de uso de emergencia (EUA) para uno
o más de estos agentes. Eso no es necesariamente malo; no significa necesariamente que el
gobierno haya puesto su pulgar en la balanza. La clave es saber si el Comité Asesor de Vacunas y
Productos Biológicos Relacionados, un grupo integrado por científicos completamente
independientes, ha examinado los datos y cuál fue el voto para su aprobación.
• Una EUA sin el respaldo del comité asesor de vacunas es una enorme bandera roja. Una EUA con
su aprobación puede ser la mejor manera de vacunar a las personas rápidamente.
• La aprobación de la vacuna es solo el primer paso. Nuestros pacientes quieren saber cuándo
podrán recibir una vacuna. Esa es una cuestión mucho más compleja y depende más de la
logística que del éxito científico. Es casi seguro que en 2021.
• ¿Cuándo se vacunará a suficientes personas para que podamos volver a la normalidad?: no se
sabe
• Eso depende no solo de la capacidad logística para hacer llegar las vacunas a quienes las
necesitan, sino de asegurar que las personas las usen. Y eso significa informes claros, honestos y
transparentes. Que se publiquen los resultados de estos ensayos. Sea abierto sobre controversias
y desacuerdos. Díganos qué efectos secundarios debemos tener en cuenta y muéstrenos un
camino claro para realizar un seguimiento de los eventos inesperados.
https://www.medscape.com/viewarticle/937337?src=soc_fb_200918_mscpedt_news_mdscp_wilson&faf=1#vp_3
https://www.medscape.com/viewarticle/937356?src=soc_fb_200916_mscpedt_news_mdscp_coronavirus&faf=1#vp_2
Covid-19 y Comorbilidades Respiratorias
https://doi.org/10.1016/j.chest.2020.05.551
Halpin et al. Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.01009-2020).
Taken together we believe these observations reinforce the need for patients with eosinophilic asthma and
COPD to continue taking their ICS containing controller therapy as that will provide optimal disease control and
perhaps also confer protection against viral triggers perhaps including SARS-CoV-2
Brian Lipworth et al. Inhaled Corticosteroids and COVID-19. AJRCCM. July 15, 2020 as 10.1164/rccm.202005-2000LE.
El Asma Durante la Pandemia por Covid-19
• Mantener el tratamiento controlador: CI
• El CI no se asocia a mayor riesgo de infección o mala evolución
• El asma se considera un FR para mala evolución
• Uso de Respirador N95 para protección
• Vacunación al día: influenza y neumococo

La EPOC Durante la Pandemia por Covid-19
• Mantener el tratamiento controlador: BD
• El CI no se asocia a mayor riesgo de infección o mala evolución pero debemos

retirarlo si no se requiere
• La EPOC se considera un FR para mala evolución

La FPI Durante la Pandemia por Covid-19
• Mantener el tratamiento controlador: soporte
• La FPI se considera un FR para mala evolución

La TB Durante la Pandemia por Covid-19
• Mantener el tratamiento antiTB
• No se ha establecido que la TB activa se considera un FR para mala evolución
• Las secuelas funcionales o anatómicas podrían ser un FR
• Uso de Respirador N95 para protección del paciente
• No olvidar que en el Perú es un país de alta prevalencia de TB por lo que no se debe

olvidar el estudio de BK y de búsqueda de sintomáticos respiratorios
Uso Rutinario de broncodilatadores inhalados
No hay recomendación a favor de indicar de manera rutinaria

broncodilatadores inhalados ya sea Beta-2 agonistas o
anticolinérgicos como prevención o como parte del tratamiento
de Covid-19
Asthma and Lower Airway Disease. Allergy. 2020;00:1–14. DOI: 10.1111/all.14517

Manejo Farmacológico de Pacientes Con Covid 20 Setiembre

Cargado por

Información del documento

Derechos de autor

Formatos disponibles

Compartir este documento

Compartir o incrustar documentos

Opciones para compartir

¿Le pareció útil este documento?

¿Este contenido es inapropiado?

Copyright:

Formatos disponibles

Manejo Farmacológico de Pacientes Con Covid 20 Setiembre

Cargado por

Copyright:

Formatos disponibles

• Por favor no abandone la sesión iniciaremos a la hora pactada

VERSIÓN 4.0: “ACTUALIZACIÓN EN EL MANEJO INTEGRAL DEL

Samuel Pecho Silva

Docente: UPCH – UDEP

Lima, 20 de septiembre 2020

aquellos aspectos que uno domina.

Antes de cometer alguno de los errores mencionados anteriormente, dejémonos guiar

Arch Bronconeumol. 2020;56(4):197–198

• Se ha evitado las siguientes falacias:

 Medidas de Prevención, Transmisión y reinfección

 Medidas de Prevención, Transmisión y reinfección

• Virus ARN con 4 géneros: los alfa y beta (mamíferos) y los

No infección (10-30%) Infección (70-90%)

Asintomático: 40% Sintomático (60%)

Leve: 80% Moderado: 10% Severo:5%

Letalidad Global: 0.6-2% Hospitalización: 20%

Published online September 11, 2020Downloaded From: https://jamanetwork.com/ on 09/19/2020

JAMA Intern Med. doi:10.1001/jamainternmed.2020.5225

medRxiv preprint doi: https://doi.org/10.1101/2020.05.28.20116129

Adjusted odds ratio

medRxiv preprint doi: https://doi.org/10.1101/2020.04.20.20054726.this version posted June 15, 2020.

Having a primary case of COVID-19 in

medRxiv preprint doi: https://doi.org/10.1101/2020.09.06.20189456.this version posted September 9, 2020

Vaccines 2020, 8, 471; doi:10.3390/vaccines8030471

• Un 40% síntomas moderados: neumonía

• Un 15% síntomas graves: neumonía severa que requieren soporte de oxígeno

• Un 5% cuadro clínico crítico presentando una o más de las siguientes complicaciones:

No infección (10-30%) Infección (70-90%)

Asintomático: 40% Sintomático (60%)

Leve: 80% Moderado: 10% Severo:5%

Letalidad Global: 0.6-2% Hospitalización: 20%

• Neutrophil • lymphocyte, monocyte, and eosinophil,

• TP, Dímero D, glucosa, ratio N/L

Ghahramani et al. Eur J Med Res (2020) 25:30

Popkin et al. Obesity Reviews. 2020;1–17

Recalde B et al. Thorax Epub ahead of print: [06/09/2020]. doi:10.1136/thoraxjnl-2020-215577

JAMA Internal Medicine Published online September 9, 2020

Carrillo-Vega et al. PLoS ONE 15(9): e0238905. https://doi.org/10.1371/journal.pone.0238905

medRxiv preprint doi: https://doi.org/10.1101/2020.09.01.20184937.this version posted September 3, 2020

Perú Primero en el mundo en número de muertos / millón de habitantes

Shields A et al. Thorax Epub ahead of print: [20/09/2020]. doi:10.1136/thoraxjnl-2020-215414

IgM e IgG: Negativo

 Medidas de Prevención, Transmisión y reinfección

 El metaanálisis se define como una técnica de revisión que se utiliza para

Arch Bronconeumol. 2020;56(4):197–198

B. Cao, DOI: 10.1056/NEJMoa2001282

www.thelancet.com Published online May 8, 2020 https://doi.org/10.1016/S0140-6736(20)31042-4

No reducción de mortalidad y No evidencia de efecto beneficio para disminuir la progresión a VM o

OMS: el 4 de julio suspende el brazo lopinavir/ritonavir del Estudio Solidarity

• Se espera en Perú un costo de 600 dólares por ampolla (extra-oficial)

• Estaría indicado en Covid-19 moderado o severo hospitalizado usando oxígeno

• An initial randomized controlled trial (RCT) was inconclusive, with a non-

Remdesivir should not be recommended for the treatment of severe COVID-19.

Piscoya y col. https://doi.org/10.1101/2020.05.26.20109595

Journal of the Chinese Medical Association Publish Ahead of Print

medRxiv preprint doi: https://doi.org/10.1101/2020.07.26.20154724

Ly et al. JAMA. Published online June 3, 2020. doi:10.1001/jama.2020.10044

• Oxygen requirements on day 14 after transfusion worsened in

• Survival also improved in plasma recipients (adjusted hazard

Is a hyperinflammatory syndrome, which can lead to a cytokine storm, tissue

• Sarilumab (Kevzara) de Sanofi y Renegeron

• Tocilizumab: 2765 dólares por 400 mg

1. www.thelancet.com Published online February 6, 2020 https://doi.org/10.1016/S0140-6736(20)30317-2

Corticosteroid treatment was associated with: