Influenza-A mediated pre-existing immunity levels to SARS-CoV-2 could predict early COVID-19 outbreak dynamics

• Published in: iScience Vol. 26; no. 12; p. 108441
• Main Authors: Almazán, Nerea Martín, Rahbar, Afsar, Carlsson, Marcus, Hoffman, Tove, Kolstad, Linda, Rönnberg, Bengt, Pantalone, Mattia Russel, Fuchs, Ilona Lewensohn, Nauclér, Anna, Ohlin, Mats, Sacharczuk, Mariusz, Religa, Piotr, Amér, Stefan, Molnár, Christian, Lundkvist, Åke, Susrud, Andres, Sörensen, Birger, Söderberg-Nauclér, Cecilia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2023; Elsevier
• Subjects: Basic Medicine; Immune response; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Virology; Immunology; Immune response; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108441

Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is highly variable and could be mediated by a cross-protective pre-immunity. We identified 14 cross-reactive peptides between SARS-CoV-2 and influenza A H1N1, H3N2, and human herpesvirus (HHV)-6A/B with potential relevance. The H1N1 peptide NGVEGF was identical to a peptide in the most critical receptor binding motif in SARS-CoV-2 spike protein that interacts with the angiotensin converting enzyme 2 receptor. About 62%–73% of COVID-19-negative blood donors in Stockholm had antibodies to this peptide in the early pre-vaccination phase of the pandemic. Seasonal flu vaccination enhanced neutralizing capacity to SARS-CoV-2 and T cell immunity to this peptide. Mathematical modeling taking the estimated pre-immunity levels to flu into account could fully predict pre-Omicron SARS-CoV-2 outbreaks in Stockholm and India. This cross-immunity provides mechanistic explanations to the epidemiological observation that influenza vaccination protected people against early SARS-CoV-2 infections and implies that flu-mediated cross-protective immunity significantly dampened the first SARS-CoV-2 outbreaks. [Display omitted] •SARS-CoV-2 susceptibility is influenced by a cross-immunity to influenza A H1N1•A common peptide, NGVEGF, provides cross-immunity between FLU strains and SARS-CoV-2•Flu-mediated antibody responses to NGVEGF prohibit SARS-CoV-2/ACE2 receptor binding•Mathematical models with pre-immunity could fully predict virus outbreak dynamics Immunology; Immune response; Virology