2020
DOI: 10.1126/science.abd4585
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Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Abstract: Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 i… Show more

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Cited by 2,302 publications
(2,316 citation statements)
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References 44 publications
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“…Two recent studies provide convincing evidence that disruption of type I IFN signaling is a frequent cause of life-threatening COVID-19. 39,40 In the first study, 650 patients with lifethreatening COVID-19 were studied by whole-exome sequencing under the hypothesis that severe COVID-19 is allelic with severe influenza 39 or that genes biologically related to these loci would be involved. 31,32 Indeed, 3.5% of patients had known (AR IRF7 and IFNAR1 deficiency, autosomal-dominant TLR3, TICAM1, TBK1, and IRF3 deficiency) and new (autosomal-dominant UNC93B1, IRF7, IFNAR1, and IFNAR2 deficiency) genetic defects abolishing induction or amplification of type I IFNs.…”
Section: Discussionmentioning
confidence: 99%
“…Two recent studies provide convincing evidence that disruption of type I IFN signaling is a frequent cause of life-threatening COVID-19. 39,40 In the first study, 650 patients with lifethreatening COVID-19 were studied by whole-exome sequencing under the hypothesis that severe COVID-19 is allelic with severe influenza 39 or that genes biologically related to these loci would be involved. 31,32 Indeed, 3.5% of patients had known (AR IRF7 and IFNAR1 deficiency, autosomal-dominant TLR3, TICAM1, TBK1, and IRF3 deficiency) and new (autosomal-dominant UNC93B1, IRF7, IFNAR1, and IFNAR2 deficiency) genetic defects abolishing induction or amplification of type I IFNs.…”
Section: Discussionmentioning
confidence: 99%
“…Being amongst the earliest and most potent of the immune responses, IFN signaling poses an immediate threat to viruses and can quickly eliminate them from the infected cells. Two recent reports have shown that inborn errors in IFN signaling and the presence of anti-IFN auto-antibodies can predispose individuals to a life-threatening COVID-19 disease, highlighting the importance of IFN immunity in SARS-CoV-2 infection 22,23 . Our findings complement these reports and show that SARS-CoV-2 has evolved a suite of mechanisms to counteract the effector functions of interferon.…”
Section: Discussionmentioning
confidence: 99%
“…This cohort included 4 patients with chronic granulomatous disease (CGD), 3 of whom did well, while one patient with concomitant Burkholderia infection died. Interrogation of the immune response in patients with severe COVID-19 has also revealed the importance of the type I interferon (IFN) pathway in controlling infection, including loss-of-function variants in genes in this pathway and neutralizing antibodies to type I IFNs [7,8]. Here, we present the case of COVID-19 in a patient with CGD and T cell deficiency due to failed hematopoietic cell transplantation (HCT) who recovered with supportive care.…”
mentioning
confidence: 99%