Selective IgA Deficiency and COVID-19 Outcomes: A Nationwide Retrospective Cohort Study

Background: Selective immunoglobulin A deficiency (sIgAD), the most common primary immunodeficiency, is associated with recurrent respiratory infections. Despite the established role of IgA in mucosal immunity, population-based data evaluating COVID-19 susceptibility and severity among individuals with sIgAD are scarce. Objectives: This study aimed to evaluate the association between selective IgA deficiency and the risk of SARS-CoV-2 infection, recurrent infection, COVID-19-related hospitalization, and vaccination uptake. Design and Setting: We conducted a retrospective population-based cohort study using the Clalit Health Services electronic health record database in Israel. Methods: Adults aged ≥18 years with documented serum IgA measurements between 2020 and 2022 were included. Selective IgA deficiency was defined as serum IgA < 7 mg/dL with normal IgG and IgM levels. Individuals with sIgAD were matched 1:4 with controls with normal IgA levels by age and sex. Outcomes included documented SARS-CoV-2 infection, recurrent infection (>2 episodes), COVID-19-related hospitalization, and vaccination status. Multivariable logistic regression models were adjusted for demographic characteristics, comorbidities, and vaccination status. Results: The matched cohort included 61,150 individuals (12,230 with sIgAD and 48,920 controls). The risk of primary SARS-CoV-2 infection did not differ significantly between groups (13.0% vs. 14.0%; adjusted OR 1.03, 95% CI 0.95-1.12). However, individuals with sIgAD had increased odds of recurrent infection (adjusted OR 1.15, 95% CI 1.09-1.22) and COVID-19-related hospitalization (adjusted OR 1.40, 95% CI 1.22-1.60). Booster vaccination uptake was slightly higher among individuals with sIgAD. Conclusions: Selective IgA deficiency was not associated with increased susceptibility to primary SARS-CoV-2 infection but was independently associated with recurrent infection and increased risk of hospitalization. These findings underscore the importance of mucosal immunity in post-infection viral control and suggest that individuals with sIgAD may benefit from closer monitoring after COVID-19 infection.