COVID-19 infection in inborn errors of immunity and their phenocopies: a systematic review and meta-analysis.

Nikan Zargarzadeh, Kiarash Saleki, Mir Saeed Yekaninejad, Amir Almasi-Hashiani, Hassan Abolhassani, Saba Fekrvand, Nima Rezaei, Ali Hakimelahi

Journal: Infectious diseases (London, England) 2025;57(6):483-517

PMID: 40178994

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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%, = 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.

Address: Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.; Student Research Committee, Babol University of Medical Sciences, Babol, Iran.; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; Division of Clinical Immunology, Department of Biosciences and Nutrition, KarolinskaInstitutet, Karolinska University Hospital, Stockholm, Sweden.; Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran.; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

DOI: 10.1080/23744235.2025.2483339