{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:36:47Z","timestamp":1774442207345,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 \u226518 years with documented serum IgA measurements between 2020 and 2022 were included. Selective IgA deficiency was defined as serum IgA &lt; 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 (&gt;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\u20131.12). However, individuals with sIgAD had increased odds of recurrent infection (adjusted OR 1.15, 95% CI 1.09\u20131.22) and COVID-19-related hospitalization (adjusted OR 1.40, 95% CI 1.22\u20131.60). 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.<\/jats:p>","DOI":"10.3390\/jcm15072487","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective IgA Deficiency and COVID-19 Outcomes: A Nationwide Retrospective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7731-118X","authenticated-orcid":false,"given":"Rawi","family":"Hazzan","sequence":"first","affiliation":[{"name":"Clalit Health Services, Afula 1834111, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nur","family":"Abu Ahmad","sequence":"additional","affiliation":[{"name":"Clalit Health Services, Afula 1834111, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mifleh","family":"Tatour","sequence":"additional","affiliation":[{"name":"Clalit Health Services, Afula 1834111, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-5683","authenticated-orcid":false,"given":"Naiel","family":"Bisharat","sequence":"additional","affiliation":[{"name":"Emek Medical Center, Afula 1834111, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziv","family":"Neeman","sequence":"additional","affiliation":[{"name":"Emek Medical Center, Afula 1834111, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020). Naming the Coronavirus Disease (COVID-19) and the Virus That Causes It, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1056\/NEJMoa030747","article-title":"Identification of a novel coronavirus in patients with severe acute respiratory syndrome","volume":"348","author":"Drosten","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"Johns Hopkins University (2025). COVID Dashboard. COVID-19 Global Cases, Johns Hopkins Coronavirus Resource Center."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jaci.2020.10.040","article-title":"Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19","volume":"147","author":"Cervia","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/mi.2007.6","article-title":"The immune geography of IgA induction and function","volume":"1","author":"Macpherson","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/path.1877","article-title":"The function of immunoglobulin A in immunity","volume":"208","author":"Woof","year":"2006","journal-title":"J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Brandtzaeg, P. (2013). Secretory IgA: Designed for anti-microbial defense. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00222"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s10875-009-9357-x","article-title":"Selective IgA deficiency","volume":"30","author":"Yel","year":"2010","journal-title":"J. Clin. Immunol."},{"key":"ref_10","first-page":"408","article-title":"Clinical and immunologic analyses of 103 patients with common variable immunodeficiency","volume":"13","year":"1993","journal-title":"J. Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Siracusano, G., Brombin, C., Pastori, C., Cugnata, F., Noviello, M., Tassi, E., Princi, D., Cantoni, D., Malnati, M.S., and Maugeri, N. (2021). Profiling Antibody Response Patterns in COVID-19: Spike S1-Reactive IgA Signature in the Evolution of SARS-CoV-2 Infection. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.772239"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Denis, J., Garnier, A., Cheutin, L., Ferrier, A., Timera, H., Jarjaval, F., Hejl, C., Billon-Denis, E., Percy ImmunoCovid Group, and Ricard, D. (2023). Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1140714"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5953","DOI":"10.1002\/jmv.27166","article-title":"Long-term monitoring of the development and extinction of IgA and IgG responses to SARS-CoV-2 infection","volume":"93","author":"Ivanov","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2022-10-4","DOI":"10.7573\/dic.2022-10-4","article-title":"Changes in nasal, pharyngeal, and salivary secretory IgA levels in patients with COVID-19, and the possibility of correcting their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms","volume":"12","author":"Kostinov","year":"2023","journal-title":"Drugs Context"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ruiz, M.J., Siracusano, G., Cottignies-Calamarte, A., Tudor, D., Real, F., Zhu, A., Pastori, C., Capron, C., Rosenberg, A.R., and Temperton, N. (2022). Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1\u03b2 associate with COVID-19 fatal outcome: A cross-sectional analysis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.842468"},{"key":"ref_16","first-page":"53","article-title":"Lupus Anticoagulant Is Associated with Critical Cases and High Mortality in COVID-19: A Literature Review","volume":"22","author":"Moafi","year":"2023","journal-title":"Tanaffos"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mellor-Pita, S., Tutor-Ureta, P., Velasco, P., Plaza, A., Diego, I., V\u00e1zquez-Comendador, J., Vionnet, A.P., Dur\u00e1n-del Campo, P., Moreno-Torres, V., and Vargas, J.A. (2024). IgA Anti-\u03b22-Glycoprotein I Antibodies as Markers of Thrombosis and Severity in COVID-19 Patients. Viruses, 16.","DOI":"10.3390\/v16071071"},{"key":"ref_18","first-page":"81","article-title":"Selective IgA deficiency in Japanese blood donors: Frequency and statistical analysis","volume":"50","author":"Kanoh","year":"1986","journal-title":"Vox Sang."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104402","DOI":"10.1016\/j.ebiom.2022.104402","article-title":"SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination","volume":"87","author":"Liew","year":"2023","journal-title":"eBioMedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40001-022-00648-5","article-title":"Immunogenicity of COVID-19 mRNA vaccines in immunocompromised patients: A systematic review and meta-analysis","volume":"27","author":"Nejad","year":"2022","journal-title":"Eur. J. Med. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Brake, S.J., Barnsley, K., Lu, W., McAlinden, K.D., Eapen, M.S., and Sohal, S.S. (2020). Smoking upregulates the ACE2 receptor, a potential adhesion site for the novel coronavirus SARS-CoV-2 (COVID-19). J. Clin. Med., 9.","DOI":"10.3390\/jcm9030841"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105426","DOI":"10.1016\/j.meegid.2023.105426","article-title":"Genetic susceptibility to severe COVID-19","volume":"110","author":"Cappadona","year":"2023","journal-title":"Infect. Genet. Evol."},{"key":"ref_23","first-page":"429","article-title":"Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference","volume":"105","author":"Zimmermann","year":"2020","journal-title":"Arch. Dis. Child."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/apa.15270","article-title":"Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults","volume":"109","author":"Ludvigsson","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3164\/jcbn.20-102","article-title":"Association between selective IgA deficiency and COVID-19","volume":"67","author":"Naito","year":"2020","journal-title":"J. Clin. Biochem. Nutr."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/7\/2487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:54:52Z","timestamp":1774432492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/7\/2487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":25,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jcm15072487"],"URL":"https:\/\/doi.org\/10.3390\/jcm15072487","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]}}}