SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 patients developing ARDS

• Published in: PloS one 2021-05, Vol.16 (5), p.e0251587-e0251587
• Main Authors: Buchholtz, Marie-Luise, Arend, Florian M, Eichhorn, Peter, Weigand, Michael, Kleinhempel, Alisa, Häusler, Kurt, Bruegel, Mathias, Holdt, Lesca M, Teupser, Daniel
• Format: Article
• Language: English
• Subjects: Acute respiratory distress syndrome; Adult; Aged; Aged, 80 and over; Analysis; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Biobanks; Biology and life sciences; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 Serological Testing; Editing; Ethics; FDA approval; Female; Funding; Humans; Immunoassay; Immunoassays; Immunoglobulin G - blood; Immunoglobulin G - immunology; Laboratories; Male; Medicine; Medicine and Health Sciences; Methodology; Middle Aged; Patients; Proteins; Regulatory agencies; Research and Analysis Methods; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - etiology; Respiratory Distress Syndrome - immunology; Risk factors; SARS-CoV-2 - immunology; SARS-CoV-2 - isolation & purification; Seroconversion; Serological tests; Serology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Viral antibodies; Viral diseases; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0251587

During the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts. 443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland). Median seroconversion occurred earlier in ARDS patients (8-9 days) than in non-ARDS patients (11-17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9%) compared to all other assays (≥98.8%) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8%) than that of Elecsys Anti-SARS-CoV-2 (100%). Serial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients.