{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:57:12Z","timestamp":1753891032683,"version":"3.41.2"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15\/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6\/17 males, 35.3%) were included. Pneumonia occurred in 4\/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17\/25): IgG<jats:sup>+<\/jats:sup> 58.8% (10\/17) (p=0.009); IgM<jats:sup>+<\/jats:sup> 41.2% (7\/17)(p&amp;lt;0.001); IgA<jats:sup>+<\/jats:sup> 52.9% (9\/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 \u00b1 4.4) vs. HC (3.5 \u00b1 1.5)(p=0.06); IgM IEI (1.9 \u00b1 2.4) vs. HC (3.9 \u00b1 2.4)(p=0.007); IgA IEI (3.3 \u00b1 4.7) vs. HC (4.6 \u00b1 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3\/11, 27.3% vs. HC: 10\/11, 90.9%; p=0.008; N-ELISpot IEI: 3\/9, 33.3% vs. HC: 11\/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 \u00b1 5.0 vs. HC 21.2 \u00b1 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 \u00b1 16.6 vs. HC: 39.1 \u00b1 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM<jats:sup>+<\/jats:sup> at 6 months was qualitatively lower in IEI(3\/8, 37.5% vs. 9\/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 \u00b1 0.9 vs. HC n=10, 2.1 \u00b1 0.9, p=0.03; IEI n=9, 1.3 \u00b1 1.5 vs. HC n=10, 2.9 \u00b1 2.8, p=0.02; and IEI n=9, 0.6 \u00b1 0.5 vs. HC n=10, 1.7 \u00b1 0.8, p=0.002 \u2013respectively) but there were no differences at remaining time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1084630","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T07:54:01Z","timestamp":1674201241000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Acute and long-term immune responses to SARS-CoV-2 infection in unvaccinated children and young adults with inborn errors of 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