Acute and long-term immune responses to SARS-CoV-2 infection in unvaccinated children and young adults with inborn errors of immunity

PurposeTo 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). MethodsUnvaccinated 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. ResultsTwenty-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(+) 58.8% (10/17) (p=0.009); IgM(+) 41.2% (7/17)(p<0.001); IgA(+) 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 +/- 4.4) vs. HC (3.5 +/- 1.5)(p=0.06); IgM IEI (1.9 +/- 2.4) vs. HC (3.9 +/- 2.4)(p=0.007); IgA IEI (3.3 +/- 4.7) vs. HC (4.6 +/- 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 +/- 5.0 vs. HC 21.2 +/- 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 +/- 16.6 vs. HC: 39.1 +/- 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM(+) 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 +/- 0.9 vs. HC n=10, 2.1 +/- 0.9, p=0.03; IEI n=9, 1.3 +/- 1.5 vs. HC n=10, 2.9 +/- 2.8, p=0.02; and IEI n=9, 0.6 +/- 0.5 vs. HC n=10, 1.7 +/- 0.8, p=0.002 -respectively) but there were no differences at remaining time points. ConclusionsOur 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.

Automated summary

This study compared the infection outcomes and immune responses to SARS-CoV-2 in unvaccinated individuals with inborn errors of immunity (IEI) and healthy individuals. The results showed that IEI patients had weaker immune responses in the acute phase of infection and lower immune responses at 6 months after infection.