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.