Figure 2. Proportion of critical COVID-19 patients with IEIs and auto-Abs against type I IFN as a function of age.

Age-specific proportions of dominant and recessive IEIs among cases of critical COVID-19 pneumonia were estimated with Bayes theorem as a function of the probability of critical COVID-19 pneumonia for IEI carriers infected with SARS-CoV-2 (i.e. the penetrance). The age-specific frequency of IEIs in the general population and the age-specific critical infection rate were taken from (158). The age-specific frequency of IEIs in the general population was estimated from the frequency of IEIs at birth, assuming a non-specific mortality rate (i.e. not attributable to COVID-19) of 0 (panel A) or 1% (panel B) per year. Based on our previous findings (67, 159, 160), the frequency of IEIs at birth was set at 10⁻³ for dominant and 5 × 10⁻⁴ for recessive IEIs. We assumed a penetrance of 0.2 for dominant IEIs and 0.8 for recessive IEIs, consistent with the larger effect size estimated for recessive than for dominant IEIs. The age-specific proportions of patients with critical COVID-19 producing auto-Abs neutralizing low doses (100 pg/mL; gray line) or high doses (10 ng/mL; black line) of IFN-α and/or IFN-ω were taken from (114).