Influenza-A mediated pre-existing immunity levels to SARS-CoV-2 could predict early COVID-19 outbreak dynamics
Nerea Martín Almazán,
Afsar Rahbar,
Marcus Carlsson,
Tove Hoffman,
Linda Kolstad,
Bengt Rönnberg,
Mattia Russel Pantalone,
Ilona Lewensohn Fuchs,
Anna Nauclér,
Mats Ohlin,
Mariusz Sacharczuk,
Piotr Religa,
Stefan Amér,
Christian Molnár,
Åke Lundkvist,
Andres Susrud,
Birger Sörensen,
Cecilia Söderberg-Nauclér
Affiliations
Nerea Martín Almazán
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden; Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 86 Huddinge Stockholm, Sweden
Afsar Rahbar
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden; Corresponding author
Marcus Carlsson
Centre for the Mathematical Sciences, Lund University, 223 62 Lund, Sweden
Tove Hoffman
Zoonosis Science Center (ZSC), Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, 1477 Uppsala, Sweden
Linda Kolstad
Zoonosis Science Center (ZSC), Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, 1477 Uppsala, Sweden
Bengt Rönnberg
Zoonosis Science Center (ZSC), Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, 1477 Uppsala, Sweden
Mattia Russel Pantalone
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden
Ilona Lewensohn Fuchs
Department of Labortory Medicine, Division of Clinical Microbiology, Karolinska Institutet, 141 86 Huddinge Stockholm, Sweden; Department of Clinical Microbiology, Karolinska University Hospital, 141 86 Huddinge Stockholm, Sweden
Anna Nauclér
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden
Mats Ohlin
Department of Immunotechnology and SciLifeLab Human Antibody Therapeutics Infrastructure Unit, Lund University, 223 62 Lund, Sweden
Mariusz Sacharczuk
Faculty of Pharmacy with the Laboratory Medicine Division, Department of Pharmacodynamics, Medical University of Warsaw, Centre for Preclinical Research and Technology, Banacha 1B, 02-091 Warsaw, Poland; Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Magdalenka, Poland
Piotr Religa
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden; Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Magdalenka, Poland
Stefan Amér
Familjeläkarna Saltsjöbaden, 133 34 Saltsjöbaden, Sweden
Christian Molnár
Familjeläkarna Saltsjöbaden, 133 34 Saltsjöbaden, Sweden; Department of Neurobiology, Care Sciences and Society, NVS, Karolinska Institutet, 171 77 Stockholm, Sweden
Åke Lundkvist
Zoonosis Science Center (ZSC), Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, 1477 Uppsala, Sweden
Andres Susrud
Immunor AS, 0349 Oslo, Norway
Birger Sörensen
Immunor AS, 0349 Oslo, Norway
Cecilia Söderberg-Nauclér
Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden; Institute of Biomedicine, Unit for Infection and Immunology, MediCity Research Laboratory, University of Turku, FI-20014 Turku, Finland; Corresponding author
Summary: 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.
