SARS-CoV-2 IgG DIAGNOSTICS

Abbott suma su apoyo a la crisis del COVID-19 al llevar rápidamente un ensayo para
la detección específica del anticuerpo IgG contra el SARS-CoV-2. Esta prueba está
diseñada por científicos de confianza y líderes de Abbott y se fabrica en volúmenes
necesarios para satisfacer las necesidades urgentes de atención continua.

ANTECEDENTES
El período de incubación medio para el SARS-CoV-2 se estima en 5 días, con un rango de 2 a 14 días.1
Los hallazgos publicados recientemente sobre pacientes ingresados con infección confirmada por SARS-CoV-2
indican que el tiempo medio para la seroconversión es de 11 a 14 días.2
No se sabe con certeza si las personas infectadas con SARS-CoV-2 que se recuperen estarán protegidas, total o
parcialmente, de una infección futura con SARS-CoV-2 o cuánto tiempo puede durar la inmunidad protectora
adquirida.3

FINALIDAD DE USO4
El ensayo SARS-CoV-2 IgG es un inmunoensayo de
micropartículas quimioluminiscentes (CMIA) utilizado para
la detección cualitativa de anticuerpos IgG contra el SARS-
CoV-2 en suero y plasma humanos en ARCHITECT i System.
El ensayo IgG SARS-CoV-2 se utiliza como ayuda en el
diagnóstico de infección por SARS-CoV-2 junto con la
evaluación clínica del paciente y otras pruebas de laboratorio.
Los resultados del ensayo IgG SARS-CoV-2 no deben usarse
como la única base para diagnóstico.

ARCHITECT SARS-CoV-2 IgG POSITIVOS CONFIRMADOS POR DÍAS

PORCENTAJE DE PACIENTES POSITIVOS DETECTADOS POR TIEMPO TRAS INICIO DE LOS
SÍNTOMAS TRAS INICIO DE LOS SÍNTOMAS

Excluídos Espécimenes Inmunocomprometidos DÍAS TRAS

Instrumento: ARCHITECT Í2000SR
PPA
INICIO DE LOS N POSITIVO NEGATIVO
100.00% SÍNTOMAS (95% CI)

86.36%
0.00%
(0.00, 60.24)

25.00%
Porcentaje detectado

(3.19, 65.09)

86.36%
25.00% (65.09, 97.09)

100.00%
(95.89, 100.00)

Cantidad Detectada:
Días tras el inicio de los síntomas:

aSe excluyeron del estudio cinco espécimenes de 1 paciente inmunocomprometido. Para obtener más información, consulte la sección LIMITACIONES DEL PROCEDIMIENTO en el prospecto. Cuando se incluyeron
los resultados de estas muestras, el PPA a 14 días tras el inicio de los síntomas fue del 96,77% (95% de IC: 90.86, 99.33).
SARS-CoV-2 IgG

ESPECIFICACIONES ARCHITECT SARS-CoV-2 IgG4,5

Inmunoensayo de micropartículas quimioluminiscentes cualitativo y de 2 pasos (CMIA)
Metodología

Tiempo para el Primer Resultado 29 minutos

Hasta 200 pruebas / hora en i2000

Rendimiento
SR

Hasta 100 pruebas / hora en i1000 SR

Interpretación de Resultados < 1.4 - Negativo

Index (S/C) ≥ 1.4 - Positivo

Precisión Control negativo: 5,9% CV

(Dentro del laboratorio) Control positivo: 1,2% CV

Confirmados Negativos
99,63%; se requiere el procesamiento de muestras en lotes
(Especificidad)

Prioridad: 75 µL; Routina: 150 µL

Volumen de Espécimen
25 µL para cada ensayo adicional

Tipo de Muestra Suero y plasma humano (EDTA)

Temperatura de la Sala entre15 y 30°C- tiempo máximo de almacenamiento de 2 días
Almacenamiento de Muestras 2 a 8°C – tiempo máximo de almacenamiento de 7 días

Abierto/Sin abrir: 2 a 8° C- hasta el vencimiento

Almacenamiento de Reactivos
A bordo: Temperatura del Sistema- tiempo máximo de almacenamiento de 7 días

INFORMACIÓN DE PEDIDOS
NOMBRE DEL PRODUCTO PRESENTACIÓN NÚMERO DE LISTA

100 kits 06R86-22

Kit de reactivos SARS-CoV-2 IgG
500 kits 06R86-32

Kit de Calibrador para SARS-CoV-2 IgG 1 Vial x 1 Nivel 06R86-02

Kit de Control para SARS-CoV-2 IgG 1 Vial Cada Uno, Positivo y Negativo 06R86-12

Los archivos de ARCHITECT SARS-CoV-2 e-Assay están disponibles en www.corelaboratory.abbott

REFERENCIAS
1. Linton NM, et al. J Clin Med. 2020;9.
2. Zhao J, et al. Pre-print. 2019. medRxiv. 2020.03.02.20030189.
3. Patel R, et al. mBio. 11:e00722-20.
4. Abbott ARCHITECT SARS-CoV-2 IgG Instructions for Use. H07891R02. April 2020.
5. ARCHITECT Systems Operations Manual. 96211-118.

ARCHITECT is a trademark of Abbott Laboratories in various jurisdictions.

All ARCHITECT analyzers are Class 1 laser products.
© 2020 Abbott Laboratories ADD-00070863
 DIAGNOSTICS

Serological approaches for the diagnosis

of SARS-CoV-2 infection

Authors: Claudio Galli, MD PhD1 and David Daghfal, MS MBA2

1
Associate Medical Director, Infectious Diseases

2
Scientific Affairs Manager

Information on SARS-CoV-2 data sourced as of 05/03/2020.

DIAGNOSTICS

OVERVIEW ON THE IMMUNE RESPONSE TO PATHOGENS

The immune system uses a complex and intricate set of pathways and processes to enable humans to fight
off pathogens. As is well documented in scientific literature, both innate and adaptive responses
constitute the human immune system. The former is a hard-wired response in the host that recognizes
molecular patterns of both pathogens and toxins. The adaptive response is driven by a genetic element
that rearranges to drive a very specific antigen binding array of molecules that are foreign to the host. The
human response to viruses uses both the innate and the adaptive arms in its attempt to rid the host of the
invading pathogen.1 The humoral response is a component of the adaptive immune response that allows
for antibodies to bind to foreign invading pathogens, marks the pathogens and their toxins for
phagocytosis and recruits further phagocytic cells to the site via the activation of the complement system
and eventually prevents the pathogen from infecting target cells. As macrophages invade the area and
bind the antibodies, they trigger a wave of cytokines that induce a more widespread systemic response. In
viruses that invade the mucosal and respiratory systems, IgA plays a role in the affected portions by early
binding to the virus triggering some of the initial less specific activation of the immune system. As the
response matures the introduction of IgM molecules drives a larger wave of cytokine production by the
invading white blood cells. As the immune response reaches full maturity more specific and higher affinity
IgG production helps the host clear the pathogen from interstitial areas and removes infected cells
displaying viral antigens on the surface.

DIAGNOSTIC APPROACHES
Clinicians and laboratorians have worked on studying viral infections to identify and characterize the
pathogens and then aid the treatment of the illnesses these viruses have caused. Utilizing direct detection
methods such as nucleic acid amplification of viral RNA or DNA, Polymerase Chain Reaction (PCR), or
immunoassays for the detection of viral antigens, usually ensures the best sensitivity for early detection of
the viral infection. Tests for human antibodies to the virus can also be used as additive or surrogate
markers to aid the diagnosis of infection but will always have a lag due to the time required for the human
body to mount its full-blown humoral response. On the other hand, as time passes from when the viral
infection has occurred, disease management and treatment will rely more on the indirect methods that
evaluate and measure the human response to the infection. In clinical practice, it is important to know at
what stage of the disease the patient is in, how fast and strong an immune response has been mounted,
and what types of antibodies are being generated (IgG and/or IgM). For these purposes, test methods that
separately look at IgM and IgG in the blood can help address those needs and make the clinical
interpretation easier.

THE IMMUNE RESPONSE TO SARS-CoV-2

The SARS-CoV-2 virus is a beta corona virus with similarities to other respiratory viruses such as MERS,
and SARS-CoV-1. Viral particles bind to the surface of the human cell and after entering the cell replicate
(RNA) and then get exocytosed. To mount an antiviral response, the innate immune system recognizes
molecular structures that are produced by the invasion of the virus. Laboratory evidence of
clinical patients showed that a specific T-cell humoral response against SARS-CoV-2 is important for the
recognition and killing of infected cells, particularly in the lungs of infected individuals. Then, this
infection induces the generation of IgG antibodies that are initially targeting the N protein and can be
detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by
day 14.2

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DIAGNOSTICS

The time course of viral and host immunity biomarkers during SARS-CoV-2 infection is described in
Figure 1. In the late incubation period and early stages, only the viral RNA, and to a lesser extent the
viral antigen, may be detected by molecular or serological techniques, respectively, that are carried out on
samples taken usually from the upper respiratory track of patients. After a few days the humoral immune
response starts to develop, overlapping the direct identification of the pathogen. While RNA detection is
the mainstay for the diagnosis of SARS-CoV-2 and allows for the diagnosis of a confirmed COVID-19 case,
RNA levels drop quickly and after a few weeks RNA and/or antigen are usually not detectable any more 3, 4,
5, especially when RNA is tested for on nasopharyngeal swabs instead of endotracheal aspirate.3 In those

instances, the laboratory support to the diagnosis may be provided only by serological assays that detect
the specific antibody responses.4, 5

Time since infection

Figure 1: Kinetics of viral and host biomarkers in SARS-CoV-2 infection

Rationale for testing IgG / IgM vs. total Ig

The possible combinations of viral and host biomarkers in SARS-CoV-2 infection and the likely
interpretation criteria are indicated in Table 1.
• In acute phase, only the separate assessment of the IgM and IgG response may provide disease
stage vs. later stages.6 This allows laboratorians and physicians to dissect the immune response
and provide clear actionable answers (Table 1).
• Combination assays may provide earlier detection, but this is not lost since the two separate
assays can still be run from the same sample at the same time on the random-access analyzers.
Currently available seroconversion data do not bring conclusive evidences on the time of
appearance of IgM vs. IgG antibodies: Tan et al4 have reported IgM to be detected earlier, but by
the time the detection of viral RNA fell under 50% of cases IgG positivity rates were higher and
would have guaranteed a better diagnostic yield (Figure 2). Conversely, on a much higher
number of patients Long et al7 have not observed an earlier detection of IgM compared to IgG and
also found higher rates of IgG positivity (Figure 3). It shall be mentioned that the cumulative

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DIAGNOSTICS

results on IgM and IgG positivity described above represent an average of many different profiles
and the individual response may vary7, as shown in the two examples on Figure 4.
• Having separate assays provides a continuum of data from infection all the way through to
recovery and will be of value when testing is carried out in asymptomatic individuals that are not
tested or test negative for viral RNA. A combined assay will not allow the assessment if the person
has been infected recently and may still harbor the virus.
• Epidemiological studies and public health studies in general will need a positive IgG response to
determine that the infection is not recent. 6,8 This type of information cannot be determined by a
total Ig assay alone.

Table 1

TEST RESULTS

GENERAL INTERPRETATION*
PCR IgM IgG

+ - - Patient may be in the initial period of infection when antibodies are not yet
produced or are under the limit of detection

+ + - Patient is in the active phase of infection has started to develop an immune

response with antibody production

- + - Patient may be in the early stage of infection. PCR result may be false-
negative or IgM false positive.

+ + + Patient is still in the active phase of the infection; immune response has
progressed.

+ - + Patient may be in the late stage of infection or has developed a recurrent

infection.

- + + Patient may be in the late or recovery stages of infection or PCR false

negative

- - + Patient may have recovered or has been infected in the past.

* Test results must be considered along with other clinical data available to the physician.

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DIAGNOSTICS

Days after the onset of symptoms

Figure 2: Positivity rates for IgM and IgG antibodies to SARS-CoV-2 in 67 patients with COVID-19. Light Blue=IgM; Dark Blue=IgG.
Data from: W. Tan et al. Viral Kinetics and Antibody Responses in Patients with COVID-19. medRxiv preprint doi:
https://doi.org/10.1101/2020.03.24.20042382

Days after the onset of symptoms

Figure 3: Positivity rates for IgM and IgG antibodies to SARS-CoV-2 in 285 patients with COVID-19. Blue=IgM; Magenta=IgG; Green=
IgM and/or IgG. Data from: Q-X Long, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nature Medicine 2020;
https://doi.org/10.1038/s41591-020-0897-1

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DIAGNOSTICS

Figure 4. Seroconversion profiles from two patients with COVID-19 disease whose samples have been assayed for SARS-CoV-2 IgM
and IgG antibodies at different time points from the onset of symptoms. In patient A, an earlier IgM response has been recorded,
while in patient B, IgG appeared first. The positivity threshold is 1 for both assays. Data from: Q-X Long, et al. Antibody responses to
SARS-CoV-2 in patients with COVID-19. Nature Medicine 2020; https://doi.org/10.1038/s41591-020-0897-1

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DIAGNOSTICS

KEY POINTS ON THE RATIONALE FOR SEPARATE IgG, IgM TESTING VS. A TOTAL Ig

1. Serology will give the treating physician insights to help enable appropriate and timely actions by
providing greater understanding as to the stage of infection. Using a total Ig assay could confuse the
picture on the patient status.
a. A PCR positive, IgM negative, and IgG negative individual may be in early stages of infection
and should be quarantined and insure healthcare workers in contact with the person have
appropriate personal protective equipment.
b. A PCR negative but IgM positive may indicate a missed (false negative PCR) this may call for a
retest on PCR or management as if in early stage of infection.
c. A PCR negative, IgM negative and IgG positive is indicative of a past infection
d. IgM presence alerts the physician that there is likely an acute infection, suggesting that clinical
action should be taken (treatment, patient isolation/quarantine, or return visit). May also be used
at locations where PCR is not readily available
The continuum of data from infection to recovery helps enable better patient assessment and
management. Understanding the magnitude of IgM vs IgG in a patient at different infection stages may
help inform a patient’s progress towards clearing the virus. Appearance of IgM and IgM titer magnitude
may also provide an indication of the cytokine storm initiation. Finally, having an IgM vs. an IgG assay
targeting different viral proteins can lend itself to confirmatory algorithms.

2. Recency of infection to help enable more accurate epidemiology studies.

An assay targeting the whole antibody response by all Ig classes cannot reliably differentiate recent
infections from more distant ones and may generate confusion on potential active infections vs. past
infections, engendering the need for further testing steps on positives. Epidemiologists and healthcare
workers will need to further elucidate the type of immune reaction that is occurring when a positive signal
for a total antibodies assay has been detected. In addition, total antibody results may lead to the
misclassification of individuals in terms of time of infection. As further data develops, it is IgG which will
eventually be used to predict immunity and protection, if longer term immunity is found to occur for
SARS CoV-2.

CONCLUSION

Serological testing helps to enable accurate diagnosis of SARS-CoV-2 infection in both symptomatic and
asymptomatic cases. While current evidence suggests that testing for IgM-class antibodies may not always
guarantee a greater yield compared to testing for IgG in the acute stages, being able to evaluate the
different Ig classes allows for a better interpretation of the different clinical stages and inform decisions
on further testing need in people with symptoms or at high risk of exposure. Since the IgG serological
response is long-lasting 1 the evaluation of an IgG antibody response appears well suited for the purpose
of population screening to assess the burden of infections and possibly to evaluate incidence and the
efficacy of prevention measures.6,8 Finally, should immunity be conferred by specific antibodies be
demonstrated for SARS-CoV-2, antibody tests together with the direct virus detection will be essential
tools in the development of de-escalation strategies in which mobility and contact restrictions can be
removed.6

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DIAGNOSTICS

REFERENCES

1. D.D. Chaplin. Overview of the immune response. Journal of Allergy and Clinical Immunology 2010; 125(Suppl 2): S3–
S23. doi:10.1016/j.jaci.2009.12.980
2. M. Rokni et al. Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS
and MERS. Reviews in Medical Virology 2020;1–6. https://doi.org/10.1002/rmv.2107
3. K.K-W. To et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody
responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infectious Diseases 2020.
https://doi.org/10.1016/S1473-3099(20)30196-1
4. W. Tan et al. Viral Kinetics and Antibody Responses in Patients with COVID-19. medRxiv preprint doi:
https://doi.org/10.1101/2020.03.24.20042382
5. L. Guo et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19): Clinical Infectious
Diseases 2020. https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa310/5810754 on 24
March 2020
6. Current performance of COVID-19 test methods and devices and proposed performance criteria, Working document
of Commission services. European Commission, 16 April 2020
7. Q-X Long, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nature Medicine 2020;
https://doi.org/10.1038/s41591-020-0897-1
8. G. Gronvall et al. Developing a National Strategy for Serology (Antibody Testing) in the United States, Published on
April 22, 2020, Johns Hopkins University

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