Infection 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.

中文翻译：

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干扰干扰素：治疗重症 COVID-19 肺炎的关键机制


感染 SARS-CoV-2 会导致临床结果，从大多数人的无症状或良性感染到少数人的严重肺炎和死亡。对患者进行的遗传学研究已证实，危重病例可能是由于 TLR3 或 TLR7 依赖性 I 型干扰素免疫的先天性错误所致，或者是由于先前存在的主要中和 IFN-α 和/或 IFN-ω 的自身抗体所致。这些发现与病毒学研究一致，病毒学研究表明多种 SARS-CoV-2 蛋白会干扰 I 型干扰素的诱导或反应途径。它们也与细胞研究和小鼠模型一致，这些研究和小鼠模型发现 I 型干扰素可以限制 SARS-CoV-2 在体外和体内的复制，而它们的缺失或减少会释放病毒的生长。总的来说，这些发现表明，在感染的最初几天，I 型干扰素不足是危重 COVID-19 肺炎的一般机制，这对治疗和未来研究的方向具有影响。