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Comment
. 2022 Jun 10:11:15.
doi: 10.12703/r-01-0000010. eCollection 2022.

Anti-type I interferon antibodies as a cause of severe COVID-19

David C Fajgenbaum  1 , Adrian C Hayday  2 , Angela J Rogers  3 , Greg J Towers  4 , Andreas Wack  5 , Ivan Zanoni  6
Affiliations
Comment

Anti-type I interferon antibodies as a cause of severe COVID-19

David C Fajgenbaum et al. Fac Rev. .

Abstract

COVID-19 ranges from asymptomatic through to respiratory failure and death. Although specific pre-existing conditions such as age and male sex have been associated with poor outcomes, we remain largely ignorant of the mechanisms predisposing to severe disease. In this study, the authors discovered that approximately 10% of 987 patients with life-threatening COVID-19 harbored neutralizing antibodies to Type I interferons (IFNs)1. They demonstrated that these antibodies could neutralize high concentrations of the corresponding IFN and could rescue SARS-CoV-2 infection from inhibition by IFN in vitro. Importantly, anti-IFN antibodies were associated with low levels of serum IFN. These observations suggest that disease severity in these individuals results from a failure to control SARS-CoV-2 replication because of antibody-mediated IFN inhibition. The study suggests specific treatments and diagnostics for this class of severe COVID-19.

Keywords: COVID-19; IFN; Interferon; SARS; anti-IFN.

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Conflict of interest statement

Adrian Hayday is a co-author and/or ongoing collaborator with Kai Kisand and Pärt Peterson, authors who contributed to the evaluated paper. He is also a Board Member and equity holder in ImmunoQure AG, a company that has identified naturally occurring human anti-cytokine antibodies targeting Type I interferon for potential use in the clinic.

Figures

Figure 1.
Figure 1.. The impact of anti-Type I IFN antibodies on COVID-19 outcomes.
The left-hand panel depicts virus-stimulated induction of Type I IFN that upon secretion protects neighboring cells from productive infection, limiting disease to a mild state. In the middle panel, the presence of Type I IFN-specific neutralizing antibodies prevents IFN engagement of neighboring cells, permitting virus infection to disseminate. Neutralization may also block immunoregulatory impacts of Type I IFN (not shown). Individually or jointly, these two impacts promote severe disease. In the right-hand panel, it is proposed that early Type I IFN supplementation (e.g., with β- or λ-IFN) can overcome the impacts of the antibodies, restoring a mild disease prognosis. It is expected that the events depicted occur in the context of Type III IFN (blue dots), and why that does not limit virus dissemination (middle panel) remains unresolved. Image credit: Ann-Kathrin Reuschl.
See this image and copyright information in PMC

Comment on

  • Autoantibodies against type I IFNs in patients with life-threatening COVID-19.
    Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19… See abstract for full author list ➔ Bastard P, et al. Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24. Science. 2020. PMID: 32972996 Free PMC article.

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