Abstract

BackgroundSARS-CoV-2 and influenza viruses continue to co-circulate, representing two major public health threats from respiratory infections with similar clinical presentations. SARS-CoV-2 and influenza vaccines can also now be co-administered. However, data on antibody responses to SARS-CoV-2 and influenza co-infection, and vaccine co-administration remains limited.MethodsWe developed a 41-plex antibody immunity assay that can simultaneously characterize antibody landscapes to SARS-CoV-2/influenza/common human coronaviruses. We analyzed sera from 840 individuals (11-93 years), including sera from reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 positive (n = 218) and negative (n = 120) cases, paired sera from SARS-CoV-2 vaccination (n = 29) and infection (n = 11), and paired sera from influenza vaccination (n = 56) and RT-PCR confirmed influenza infection (n = 158) cases. Lastly, we analyzed sera collected from 377 individual that exhibited acute respiratory illness (ARI) in 2020.ResultsThis 41-plex assay has high sensitivity and specificity in detecting SARS-CoV-2 infections. It differentiated SARS-CoV-2 vaccination (antibody responses only to spike protein) from infection (antibody responses to both spike and nucleoprotein). No cross-reactive antibodies were detected to SARS-CoV-2 from influenza vaccination and infection, and vice versa, suggesting no interaction between SARS-CoV-2 and influenza antibody responses. However, cross-reactive antibodies were detected between spike proteins of SARS-CoV-2 and common human coronaviruses that were removed by serum adsorption. Among 377 individual who exhibited ARI in 2020, 129 were influenza positive, none had serological evidence of SARS-CoV-2/influenza co-infections.ConclusionsMultiplex detection of antibody landscapes can provide in-depth analysis of the antibody protective immunity to SARS-CoV-2 in the context of other respiratory viruses including influenza.

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