Subjects who developed SARS-CoV-2 specific IgM after vaccination show a longer humoral immunity and a lower frequency of infection

• Published in: EBioMedicine Vol. 89; p. 104471
• Main Authors: Piubelli, Chiara, Ruggiero, Alessandra, Calciano, Lucia, Mazzi, Cristina, Castilletti, Concetta, Tiberti, Natalia, Caldrer, Sara, Verzè, Matteo, Longoni, Silvia Stefania, Accordini, Simone, Bisoffi, Zeno, Zipeto, Donato
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023; The Author(s). Published by Elsevier B.V
• Subjects: Advanced Basic Science; Antibodies, Viral; Breakthrough infection; BTN162b2 vaccine; COVID-19; Humans; IgG; IgM; Immunity, Humoral; Immunoglobulin G; Immunoglobulin M; Internal Medicine; SARS-CoV-2; Spike; Vaccination; COVID-19; Spike; SARS-CoV-2; IgG; BTN162b2 vaccine; IgM; Breakthrough infection
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2023.104471

We have previously shown that eliciting SARS-CoV-2-specific IgM after vaccination is associated with higher levels of SARS-CoV-2 neutralizing IgG. This study aims to assess whether IgM development is also associated with longer-lasting immunity. We analysed anti-SARS-CoV-2 spike protein IgG and IgM (IgG-S, IgM-S), and anti-nucleocapsid IgG (IgG-N) in 1872 vaccinees at different time points: before the first dose (D1; w0), before the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; moreover, 109 subjects were further tested at the booster dose (D3, w44), at 3 weeks (w47) and 6 months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels. In subjects who had no evidence of a previous infection at D1 (non-infected, NI), IgM-S development after D1 and D2 was associated with higher IgG-S levels at short (w6, p < 0.0001) and long (w29, p < 0.001) follow-up. Similar IgG-S levels were observed after D3. The majority (28/33, 85%) of the NI subjects who had developed IgM-S in response to vaccination did not experience infection. The development of anti-SARS-CoV-2 IgM-S following D1 and D2 is associated with higher IgG-S levels. Most individuals who developed IgM-S never became infected, suggesting that IgM elicitation may be associated with a lower risk of infection. “Fondi Ricerca Corrente” and “Progetto Ricerca Finalizzata” COVID-2020 (Italian Ministry of Health); FUR 2020 Department of Excellence 2018–2022 (MIUR, Italy); the Brain Research Foundation Verona.