A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations

• Published in: Science translational medicine Vol. 12; no. 559
• Main Authors: Grzelak, Ludivine, Temmam, Sarah, Planchais, Cyril, Demeret, Caroline, Tondeur, Laura, Huon, Christèle, Guivel-Benhassine, Florence, Staropoli, Isabelle, Chazal, Maxime, Dufloo, Jeremy, Planas, Delphine, Buchrieser, Julian, Rajah, Maaran Michael, Robinot, Remy, Porrot, Françoise, Albert, Mélanie, Chen, Kuang-Yu, Crescenzo-Chaigne, Bernadette, Donati, Flora, Anna, François, Souque, Philippe, Gransagne, Marion, Bellalou, Jacques, Nowakowski, Mireille, Backovic, Marija, Bouadma, Lila, Le Fevre, Lucie, Le Hingrat, Quentin, Descamps, Diane, Pourbaix, Annabelle, Laouénan, Cédric, Ghosn, Jade, Yazdanpanah, Yazdan, Besombes, Camille, Jolly, Nathalie, Pellerin-Fernandes, Sandrine, Cheny, Olivia, Ungeheuer, Marie-Noëlle, Mellon, Guillaume, Morel, Pascal, Rolland, Simon, Rey, Felix A, Behillil, Sylvie, Enouf, Vincent, Lemaitre, Audrey, Créach, Marie-Aude, Petres, Stephane, Escriou, Nicolas, Charneau, Pierre, Fontanet, Arnaud, Hoen, Bruno, Bruel, Timothée, Eloit, Marc, Mouquet, Hugo, Schwartz, Olivier, van der Werf, Sylvie
• Format: Journal Article
• Language: English
• Published: United States 02.09.2020
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral - blood; Betacoronavirus - immunology; Clinical Laboratory Techniques - methods; Cohort Studies; Coronavirus Infections - diagnosis; Coronavirus Infections - epidemiology; Coronavirus Infections - immunology; COVID-19; COVID-19 Testing; Enzyme-Linked Immunosorbent Assay - methods; Female; Flow Cytometry - methods; France - epidemiology; Healthy Volunteers; Humans; Immunoprecipitation - methods; Luciferases; Male; Middle Aged; Neutralization Tests; Pandemics; Pneumonia, Viral - diagnosis; Pneumonia, Viral - epidemiology; Pneumonia, Viral - immunology; SARS-CoV-2; Seroepidemiologic Studies; Serologic Tests - methods; Spike Glycoprotein, Coronavirus - immunology; Translational Research, Biomedical; Young Adult; France
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.abc3103

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.