{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:53:04Z","timestamp":1773978784984,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44\u20133.53) risk ratio for hospital admission and a higher mortality ratio (2.4% <jats:italic>vs.<\/jats:italic> 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.<\/jats:p>","DOI":"10.3389\/fimmu.2022.835770","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T04:34:49Z","timestamp":1646022889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Tomas","family":"Milota","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Sobotkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitka","family":"Smetanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marketa","family":"Bloomfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Vydlakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zita","family":"Chovancova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Litzman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Hakl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Novak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Malkusova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Hanzlikova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalibor","family":"Jilek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Hutyrova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitezslav","family":"Novak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Krcmova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sediva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavlina","family":"Kralickova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s10875-019-00737-x","article-title":"Human Inborn Errors of Immunity: 2019 Update on the Classification From the International Union of Immunological Societies Expert Committee","volume":"40","author":"Tangye","year":"2020","journal-title":"J Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1586\/1744666X.2015.990440","article-title":"Important Differences in the Diagnostic Spectrum of Primary Immunodeficiency in Adults Versus Children","volume":"11","author":"Abolhassani","year":"2015","journal-title":"Expert Rev Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.45053","article-title":"SARS-CoV-2: An Emerging Coronavirus That Causes a Global Threat","volume":"16","author":"Zheng","year":"2020","journal-title":"Int J Biol Sci"},{"key":"B5","unstructured":"WHO Coronavirus (COVID-19) Dashboard2021"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-020-01760-4","article-title":"Clinical Manifestations of COVID-19 in the General Population: Systematic Review","volume":"133","author":"Da Rosa Mesquita","year":"2021","journal-title":"Wien Klin Wochenschr"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2020.582932","article-title":"Coronavirus Disease (COVID-19): Comprehensive Review of Clinical Presentation","volume":"8","author":"Mehta","year":"2020","journal-title":"Front Public Health"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247461","article-title":"Population Risk Factors for Severe Disease and Mortality in COVID-19: A Global Systematic Review and Meta-Analysis","volume":"16","author":"Booth","year":"2021","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.03.017","article-title":"Prevalence of Comorbidities and its Effects in Patients Infected With SARS-CoV-2: A Systematic Review and Meta-Analysis","volume":"94","author":"Yang","year":"2020","journal-title":"Int J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00575-4","article-title":"Assessment of Protection Against Reinfection With SARS-CoV-2 Among 4 Million PCR-Tested Individuals in Denmark in 2020: A Population-Level Observational Study","volume":"397","author":"Hansen","year":"2021","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.05.022","article-title":"Novel SARS-CoV-2 Variants: The Pandemics Within the Pandemic","volume":"27","author":"Boehm","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2021.01.022","article-title":"COVID-19 in Immunocompromised Patients: A Systematic Review of Cancer, Hematopoietic Cell and Solid Organ Transplant Patients","volume":"82","author":"Belsky","year":"2021","journal-title":"J Infect"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.614086","article-title":"Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel","volume":"11","author":"Marcus","year":"2020","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.jaci.2020.12.620","article-title":"COVID-19 in Patients With Primary and Secondary Immunodeficiency: The United Kingdom Experience","volume":"147","author":"Shields","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01077-5","article-title":"COVID-19 in the Context of Inborn Errors of Immunity: A Case Series of 31 Patients From Mexico","volume":"41","author":"Castano-Jaramillo","year":"2021","journal-title":"J Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.09.010","article-title":"Coronavirus Disease 2019 in Patients With Inborn Errors of Immunity: An International Study","volume":"147","author":"Meyts","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01066-8","article-title":"Outcome of SARS-CoV-2 Infection in 121 Patients With Inborn Errors of Immunity: A Cross-Sectional Study","volume":"41","author":"Goudouris","year":"2021","journal-title":"J Clin Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.004","article-title":"The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity","volume":"7","author":"Seidel","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B19","unstructured":"Covid-19 Epidemic in the Czech Republic2021"},{"key":"B20","unstructured":"Population Change - 1st Quarter of 20212021"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/science.abd4570","article-title":"Inborn Errors of Type I IFN Immunity in Patients With Life-Threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.05.017","article-title":"Impacts of Immunosuppression and Immunodeficiency on COVID-19: A Systematic Review and Meta-Analysis","volume":"81","author":"Gao","year":"2020","journal-title":"J\u00a0Infect"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.08.016","article-title":"Antibody Responses to the SARS-CoV-2 Vaccine in Individuals With Various Inborn Errors of Immunity","volume":"148","author":"Delmonte","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15154","article-title":"A Lesson From a Saboteur: High-MW Kininogen Impact in Coronavirus-Induced Disease 2019","volume":"177","author":"Colarusso","year":"2020","journal-title":"Br J Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000967","article-title":"A Hypothesized Role for Dysregulated Bradykinin Signaling in COVID-19 Respiratory Complications","volume":"34","author":"Roche","year":"2020","journal-title":"FASEB J"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2020.100454","article-title":"Does Hereditary Angioedema Make COVID-19 Worse","volume":"13","author":"Xu","year":"2020","journal-title":"World Allergy Organ J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.11.042","article-title":"COVID-19 Affecting Hereditary Angioedema Patients With and Without C1 Inhibitor Deficiency","volume":"9","author":"Grumach","year":"2021","journal-title":"J Allergy Clin Immunol Pract"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.835770\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T04:34:51Z","timestamp":1646022891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.835770\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2022.835770"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.835770","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]},"article-number":"835770"}}