期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：11
DOI：10.1073/pnas.2116730119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The interferon (IFN) family of proteins plays key roles in the immune response against viruses and other pathogens. In the context of COVID-19, IFNs have been shown to be key for restraining SARS-CoV-2 infection but have also been described as drivers of severe symptoms. However, it is not fully understood how each member of the IFN family contributes to distinct aspects of COVID-19. We report here the results of a deep examination of 12 different IFNs in hospitalized COVID-19 patients, which revealed clear differences among IFNs in their associations with molecular, cellular, and physiological processes relevant to COVID-19 presentation.
The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation of systemic IFN signaling in hospitalized COVID-19 patients, defining the multiomics biosignatures associated with varying levels of 12 different type I, II, and III IFNs. The antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of IFNs, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage and platelet activation associate with high levels of IFNB1 and IFNA6. Seroconversion and time since hospitalization associate with a significant decrease in a specific subset of IFNs. Additionally, differential IFN subtype production is linked to distinct constellations of circulating myeloid and lymphoid immune cell types. Each IFN has a unique metabolic signature, with IFNG being the most associated with activation of the kynurenine pathway. IFNs also show differential relationships with clinical markers of poor prognosis and disease severity. For example, whereas IFNG has the strongest association with C-reactive protein and other immune markers of poor prognosis, IFNB1 associates with increased neutrophil to lymphocyte ratio, a marker of late severe disease. Altogether, these results reveal specialized IFN action in COVID-19, with potential diagnostic and therapeutic implications.
