RESUMEN
Coronavirus disease 19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the clinical correlations of antibodies produced by infected individuals will be critical for incorporating antibody results into clinical management. This study was an observational cohort study to evaluate antibody responses in individuals with PCR-confirmed COVID-19, including 48 hospitalized patients diagnosed with COVID-19 by real-time polymerase chain reaction (RT-PCR) at a large tertiary care medical center. Serum samples were obtained from patients at various time points during the disease course and tested for IgM and IgG antibodies against SARS-CoV-2. Medical records were reviewed, and antibody levels were compared with clinical and laboratory findings. Patients did not have high levels of antibodies within one week of symptoms, but most had detectable IgM and IgG antibodies between 8 and 29 days after onset of symptoms. Some individuals did not develop measurable levels of IgM or IgG antibodies. IgM antibodies were associated with elevated ALT, but there were no other significant associations. We did not observe significant associations of SARS-CoV-2 antibodies with clinical outcomes, including intubation and death. SARS-CoV-2 IgM and IgG antibodies were unlikely to be detected in the first week of infection or in severely immunocompromised individuals. Although we did not observe associations with clinical outcomes, IgM antibodies were associated with higher ALT levels. Antibody production reflects the virus-specific immune response, which is important for immunity but also drives pathology, and antibody levels may be important for guiding treatment of individuals with COVID-19.
RESUMEN
BackgroundSeroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. MethodsWe evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. ResultsThe Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH assays were less sensitive during early disease, particularly among immunosuppressed individuals. ConclusionsThe Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives. SummarySARS-CoV-2 immunoassays can be valuable tools for informing the global response, but many currently available assays have not been independently validated. We conducted a performance assessment of four assays including the Roche Diagnostics and Epitope Diagnostics immunoassays.