Available online 14 September 2022, 102252

SARS-CoV-2 and influenza A virus dysregulate human innate immune responses.

Severe COVID-19 and severe influenza exhibit distinct cytokine patterns.

Delayed IFN production along with sustained inflammation drives severe COVID-19.

MDA5 and RIG-I are key innate immune sensors of SARS-CoV-2 and influenza A virus.

SARS-CoV-2 and influenza A virus have evolved effective interferon antagonisms.

The outbreak of the COVID-19 pandemic one year after the centennial of the 1918 influenza pandemic reaffirms the catastrophic impact respiratory viruses can have on global health and economy. A key feature of SARS-CoV-2 and influenza A viruses is their remarkable ability to suppress or dysregulate human immune responses. Here, we summarize the growing knowledge about the interplay of SARS-CoV-2 and antiviral innate immunity, with an emphasis on the regulation of type I or III interferon responses that are critically implicated in COVID-19 pathogenesis. Furthermore, we draw parallels to influenza A virus infection and discuss shared innate immune sensing mechanisms and the respective viral countermeasures.

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