Background: SARS-CoV-2 has infected more than 450 million people around the world. In about 10% of cases, the infection leads to hypoxemic pneumonia, which is much rarer in children, while multisystem inflammation is seen almost only in children. Methods: We evluated 31 young patients (0.5-19 years) who had both pre-existing inborn errors of immunity (IEI) and were later diagnosed with COVID-19 complications. Whole-exome sequencing was performed, SARS-CoV-2 specific antibodies and autoantibody against type I interferons were measured and plasma inflammatory factors were profiled. We also reviewed COVID-19 disease severity and outcome in IEI patients in the literature. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%). The IgM and IgG-specific antibody response against the spike protein of the virus was positive in 14 (66.6%) of the IEI patients tested. Autoantibodies neutralizing type I interferons were identified in the plasma of two patients (6.8% of tested samples). Five patients fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children (MIS-C). Eleven patients (35.4%) died due to COVID-19 complications showing a 3000 fold higher mortality rate compared to normal COVID-19 death rate in children (0.01%). For the additional 696 IEI patients reported till date, severe presentation of COVID-19 was observed in 23.3% of cases. Furthermore, a 5-fold higher mortality rate was observed, when compared with global infection-fatality reports. Conclusions: Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to better understand the human innate and adaptive immune response against SARS-CoV-2, which may assist to develop better preventive and therapeutic strategies.