LAUSR

Background Although influenza vaccines provide protection against influenza viruses, concern has been raised that they may increase susceptibility to non-influenza respiratory viruses. As pandemic lockdowns end, temporal overlap of circulation of seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expected. Understanding the impact of influenza vaccination on risk of coronavirus infection is therefore of considerable public health importance. Methods We performed a secondary analysis of a randomized trial where children and adolescents in Canadian Hutterite colonies were randomly assigned by colony to receive the 2008-2009 seasonal inactivated trivalent influenza vaccine (TIV) or a control hepatitis A (HepA) vaccine. All 3,273 colony members (vaccinated children and nonvaccine recipients) were followed for the primary outcome of RT-PCR confirmed seasonal coronavirus infection. Serum collected pre- and post-vaccination was analyzed for titers of IgG antibodies towards human coronaviruses (HCoV). Results The incidence of coronavirus infection was 0·18/1000 person-days in the colonies that received TIV vs 0·36/1000 person-days in the control group, hazard ratio (HR) 0·49 [0·21-1·17]. The risk reduction among non-vaccine recipients in the TIV group compared to the control group was HR 0·55 [0·24-1·23]. There was an increase in the geometric mean fold change of HCoV-OC43 antibody titers following TIV compared to HepA vaccine (mean difference 1·2 [0·38-2·06], p=0·007), and an increase in geometric mean HCoV-NL63 antibody titers post-TIV (262·9 vs 342·9, p=0·03). Conclusion The influenza vaccine does not increase the risk of a coronavirus infection. Instead, the influenza vaccine may reduce the rate of coronavirus infections by inducing cross-reactive anti-coronavirus IgG antibodies.