Etiologies are unknown for four of the seven enigmas: resistance to infection (and silent infection), pandemic chilblains (although a mechanism of disease is documented), long COVID, and mRNA vaccine–induced myocarditis. There are etiologies for the other three enigmas. Hypoxemic COVID-19 pneumonia is explained in 15–20% of cases by inborn errors of or autoantibodies against type I IFNs. MIS-C is explained in 1–2% of cases by other inborn errors. Only one patient with neuro-COVID is understood etiologically.