Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection

Pelleau, Stéphane; Woudenberg, Tom; Rosado, Jason; Donnadieu, Françoise; Garcia, Laura; Obadia, Thomas; Gardais, Soazic; Elgharbawy, Yasmine; Velay, Aurelie; Gonzalez, Maria; Nizou, Jacques Yves; Khelil, Nizar; Zannis, Konstantinos; Cockram, Charlotte; Merkling, Sarah Hélène; Meola, Annalisa; Kerneis, Solen; Terrier, Benjamin; de Seze, Jerome; Planas, Delphine; Schwartz, Olivier; Dejardin, François; Petres, Stéphane; von Platen, Cassandre; Pellerin, Sandrine Fernandes; Arowas, Laurence; de Facci, Louise Perrin; Duffy, Darragh; Cheallaigh, Clíona Ní; Dunne, Jean; Conlon, Niall; Townsend, Liam; Duong, Veasna; Auerswald, Heidi; Pinaud, Laurie; Tondeur, Laura; Backovic, Marija; Hoen, Bruno; Fontanet, Arnaud; Mueller, Ivo; Fafi-Kremer, Samira; Bruel, Timothée; White, Michael

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%–94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%–89%) anti-RBD IgG remains, and 7% (1%–31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0–3 months, 3–6 months, and 6–12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.