RESPIRATORY DISEASE FACTORS LINK WITH REDUCED SARS-CoV-2 SUSCEPTIBILITY IN PWH

ABSTRACT

Background: Despite favorable vaccine responses of people with HIV (PWH), susceptibility to SARS-CoV-2 (SCv2) infection and increased risk of COVID-19 in immunocompromised PWH continue to be of concern. Here, we searched the Swiss HIV Cohort Study (SHCS) with>9500 actively enrolled, optimally treated PWH to identify factors associated with SCv2 infection in the pre-and postvaccination area. Method(s) We utilized information on SCv2 events reported to the SHCS in 2020 -2021. To detect asymptomatic infection, we screened pre-pandemic (2019) and pandemic (2020-2021) bio-banked plasma for SCv2 antibodies (Ab). SCv2+ and matched SCv2- PWH were additionally screened for Abs to circulating human coronaviruses (HCoV). Data were compared to HIV negative (HIV-) controls. SCv2 data and >26 behavioral, immunologic and disease-parameters available in the SHCS data base were analyzed by logistic regression, conditional logistic regression, and Bayesian multivariate regression. Result(s) Considering information on the SCv2 status of 6270 SHCS participants, neither HIV-1 viral load nor CD4+ T cell levels were linked with increased SCv2 infection risk. COVID-19-linked hospitalization (87/982) and case fatality rates (8/982) were low, but slightly higher than in the general Swiss population when stratified by age. Compared to HIV-, PWH had lower SCv2 IgG responses (median effect size= -0.48, 95%-Credibility-Interval=[-0.7, -0.28]). Consistent with earlier findings, high HCoV Abs pre-pandemic (2019) were associated with a lower risk of a subsequent SCv2-infection and, in case or infection, with higher Ab responses. Examining behavioral factors unrelated to the HIV-status, people living in single-person households were less at risk of SCv2 infection (aOR= 0.77 [0.66,0.9]). We found a striking, highly significant protective effect of smoking on SCv2 infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14) which was strongest in 2020 prior to vaccination and was even comparable to the effect of early vaccination in 2021. This impact of smoking was highly robust, occurred even in previous smokers and was highest for heavy smokers. Conclusion(s) Our unbiased cohort screen identified two controversially discussed factors, smoking and cross-protection by HCoV responses to be linked with reduced susceptibility to SCv2, validating their effect for the general population. Overall weaker SCv2 Ab responses in PWH are of concern and need to be monitored to ensure infection- and vaccine-mediated protection from severe disease.