Covid-19 Infection in Inborn Errors of Immunity and Their Phenocopies: A Systematic Review and Meta-Analysis Publisher



Fekrvand S^{1, 2} ; Saleki K^{1, 2, 3} ; Abolhassani H^{1, 4} ; Almasihashiani A⁵ ; Hakimelahi A¹ ; Zargarzadeh N⁶ ; Yekaninejad MS⁷ ; Rezaei N^{1, 2} Show Affiliations
Source: Infectious Diseases Published:2025

Abstract

Background: Inborn errors of immunity (IEI) are congenital disorders of the immune system. Due to impaired immune system, they are at a higher risk to develop a more severe COVID-19 course compared to general population. Objectives: Herein, we aimed to systematically review various aspects of IEI patients infected with SARS-CoV-2. Moreover, we performed a meta-analysis to determine the frequency of COVID-19 in patients with different IEI. Methods: Embase, Web of Science, PubMed, and Scopus were searched introducing terms related to IEI and COVID-19. Results: 3646 IEI cases with a history of COVID-19 infection were enrolled. The majority of patients had critical infections (1013 cases, 27.8%). The highest frequency of critical and severe cases was observed in phenocopies of IEI (95.2%), defects in intrinsic and innate immunity (69.4%) and immune dysregulation (23.9%). 446 cases (12.2%) succumbed to the disease and the highest mortality was observed in IEI phenocopies (34.6%). COVID-19 frequency in immunodeficient patients was 11.9% (95% CI: 8.3 to 15.5%) with innate immunodeficiency having the highest COVID-19 frequency [34.1% (12.1 to 56.0%)]. COVID-19 case fatality rate among IEI patients was estimated as 5.4% (95% CI: 3.5–8.3%, n = 8 studies, I2 = 17.5%). Conclusion: IEI with underlying defects in specific branches of the immune system responding to RNA virus infection experience a higher frequency and mortality of COVID-19 infection. Increasing awareness about these entities and underlying genetic defects, adherence to prophylactic strategies and allocating more clinical attention to these patients could lead to a decrease in COVID-19 frequency and mortality in these patients. © 2025 Society for Scandinavian Journal of Infectious Diseases.