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

doi:10.1016/j.isci.2023.108441

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

iScience. 2023 Nov 14;26(12):108441. doi: 10.1016/j.isci.2023.108441. eCollection 2023 Dec 15.

Authors

Nerea Martín Almazán^{1

2

3}, Afsar Rahbar^{1

2}, Marcus Carlsson⁴, Tove Hoffman⁵, Linda Kolstad⁵, Bengt Rönnberg⁵, Mattia Russel Pantalone^{1

2}, Ilona Lewensohn Fuchs^{6

7}, Anna Nauclér¹, Mats Ohlin⁸, Mariusz Sacharczuk^{9

10}, Piotr Religa^{1

2

10}, Stefan Amér¹¹, Christian Molnár^{11

12}, Åke Lundkvist⁵, Andres Susrud¹³, Birger Sörensen¹³, Cecilia Söderberg-Nauclér^{1

2

14}

Affiliations

¹ Department of Medicine, Unit for Microbial Pathogenesis, Karolinska Institutet, 17164 Solna, Stockholm, Sweden.
² Department of Neurology, Karolinska University Hospital, 171 76 Solna Stockholm, Sweden.
³ Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 86 Huddinge Stockholm, Sweden.
⁴ Centre for the Mathematical Sciences, Lund University, 223 62 Lund, Sweden.
⁵ Zoonosis Science Center (ZSC), Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, 1477 Uppsala, Sweden.
⁶ Department of Labortory Medicine, Division of Clinical Microbiology, Karolinska Institutet, 141 86 Huddinge Stockholm, Sweden.
⁷ Department of Clinical Microbiology, Karolinska University Hospital, 141 86 Huddinge Stockholm, Sweden.
⁸ Department of Immunotechnology and SciLifeLab Human Antibody Therapeutics Infrastructure Unit, Lund University, 223 62 Lund, Sweden.
⁹ 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.
¹⁰ Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Postępu 36A, 05-552 Magdalenka, Poland.
¹¹ Familjeläkarna Saltsjöbaden, 133 34 Saltsjöbaden, Sweden.
¹² Department of Neurobiology, Care Sciences and Society, NVS, Karolinska Institutet, 171 77 Stockholm, Sweden.
¹³ Immunor AS, 0349 Oslo, Norway.
¹⁴ Institute of Biomedicine, Unit for Infection and Immunology, MediCity Research Laboratory, University of Turku, FI-20014 Turku, Finland.

Abstract

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.

Keywords: Immune response; Immunology; Virology.