SARS-CoV-2 infection in a pediatrics STAT1 GOF patient under Ruxolitinib therapy-a matter of balance?

Abstract

Recently, 94 inborn errors of immunity (IEI) patients suffering from COVID-19 have been described, overall demonstrating a mild phenotype [1] although more severe disease manifestations have been suggested for patients with alterations in the interferon (IFN) signaling pathway, including auto-antibodies against type I IFN [2]. Patients with STAT1 GOF mutations show a complex and often severe phenotype, combining an increased susceptibility of fungal, (myco-) bacterial and viral infections as well as autoimmune and autoinflammatory manifestations [3]. Characteristically, in response to type I and type II IFN stimulation, these patients show STAT1 hyperphosphorylation [3, 4]. Whether in the context of SARS-CoV-2 infection, the hyperactivation of the IFN-JAK1/2-STAT1 pathway would be protective (antiviral effect) or deleterious (hyperinflammation) is unclear. Ruxolitinib (a selective JAK1/2 inhibitor) has been successfully used in STAT1 GOF patients controlling many disease manifestations [5] and also resulted in improved pulmonary function and faster recovery from lymphopenia in previously healthy individuals suffering from severe COVID-19