IFN-α2a Therapy in Two Patients with Inborn Errors of TLR3 and IRF3 Infected with SARS-CoV-2

Excerpt

We recently reported that inborn errors of the TLR3- and IRF7-dependent production and amplification of type I interferons (IFNs) confer a predisposition to life-threatening COVID-19 pneumonia [1]. Inborn errors of eight genes were found to be causal: five from the TLR3-dependent pathway of induction (TLR3, TICAM1, UNC93B1, TBK1, IRF3), and three governing type I IFN induction and amplification (IRF7, IFNAR1, IFNAR2). These inborn errors include autosomal recessive (AR) (IRF7, IFNAR1) and autosomal dominant (AD) disorders (TLR3, TICAM1, UNC93B1, TBK1, IRF3, IRF7, IFNAR1, IFNAR2). Four of the disorders observed had not previously been described (AD UNC93B, IRF7, IFNAR1 and IFNAR2 deficiencies), whereas the other six (AR IRF7 and IFNAR1 deficiencies, and AD TLR3, TICAM1, TBK1 and IRF3 deficiencies) had previously been reported in patients with severe influenza pneumonitis, herpes simplex encephalitis (HSE), or adverse reactions to live attenuated viral vaccines [1]. These findings suggested that early type I IFN administration might be beneficial in selected patients known to harbor one of the inborn errors known to affect the production or amplification of type I IFN. …