Interfering with Interferons: A Critical Mechanism for Critical COVID-19 Pneumonia

Annu Rev Immunol. 2023 Apr 26;41:561-585. doi: 10.1146/annurev-immunol-101921-050835.ABSTRACTInfection with SARS-CoV-2 results in clinical outcomes ranging from silent or benign infection in most individuals to critical pneumonia and death in a few. Genetic studies in patients have established that critical cases can result from inborn errors of TLR3- or TLR7-dependent type I interferon immunity, or from preexisting autoantibodies neutralizing primarily IFN-α and/or IFN-ω. These findings are consistent with virological studies showing that multiple SARS-CoV-2 proteins interfere with pathways of induction of, or response to, type I interferons. They are also congruent with cellular studies and mouse models that found that type I interferons can limit SARS-CoV-2 replication in vitro and in vivo, while their absence or diminution unleashes viral growth. Collectively, these findings point to insufficient type I interferon during the first days of infection as a general mechanism underlying critical COVID-19 pneumonia, with implications for treatment and directions for future research.PMID:37126418 | DOI:10.1146/annurev-immunol-101921-050835
Source: Annual Review of Immunology - Category: Allergy & Immunology Authors: Source Type: research