Autoantibodies against type I IFNs in patients with life-threatening COVID-19

@article{Bastard2020AutoantibodiesAT,
  title={Autoantibodies against type I IFNs in patients with life-threatening COVID-19},
  author={P. Bastard and Lindsey B. Rosen and Q. Zhang and E. Michailidis and H. Hoffmann and Y. Zhang and K. Dorgham and Q. Philippot and J. Rosain and V. B{\'e}ziat and J. Manry and E. Shaw and Liis Haljasm{\"a}gi and P. Peterson and L. Lorenzo and Lucy Bizien and S. Trouillet-Assant and K. Dobbs and A. D. de Jesus and A. Belot and A. Kallaste and {\'E}. Catherinot and Y. Tandjaoui-Lambiotte and J{\'e}r{\'e}mie Le Pen and Gaspard Kerner and B. Bigio and Y. Seeleuthner and Rui Yang and A. Bolze and A. Spaan and O. Delmonte and M. Abers and A. Aiuti and G. Casari and V. Lampasona and L. Piemonti and F. Ciceri and K. Bilguvar and R. Lifton and M. Vasse and D. Smadja and M. Migaud and J. Hadjadj and B. Terrier and D. Duffy and L. Quintana-Murci and D. van de Beek and Lucie Roussel and D. Vinh and S. Tangye and F. Haerynck and D. Dalmau and J. Martinez-Picado and P. Brodin and M. Nussenzweig and S. Boisson-Dupuis and C. Rodr{\'i}guez-Gallego and G. Vogt and T. Mogensen and A. Oler and Jingwen Gu and P. Burbelo and Jeffrey I. Cohen and A. Biondi and L. Bettini and Mariella D'angi{\`o} and P. Bonfanti and P. Rossignol and J. Mayaux and F. Rieux-Laucat and E. Husebye and F. Fusco and M. Ursini and L. Imberti and A. Sottini and S. Paghera and E. Quiros-Roldan and Camillo Rossi and R. Castagnoli and D. Montagna and A. Licari and G. Marseglia and X. Duval and J. Ghosn and J. Tsang and R. Goldbach-Mansky and K. Kisand and M. Lionakis and A. Puel and S. Zhang and S. Holland and G. Gorochov and E. Jouanguy and C. Rice and A. Cobat and L. Notarangelo and L. Abel and H. Su and J. Casanova},
  journal={Science (New York, N.y.)},
  year={2020},
  volume={370}
}
The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this… Expand
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
TLDR
The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001. Expand
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TLDR
Findings indicate that impaired type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 13% of patients, and pave the way for further research into unexplained severe cases, and provide a rationale for preventing and treating the disease in individuals at risk, with recombinanttype I IFNs. Expand
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It is shown that auto-Abs against IFN-I that are not neutralizing in vitro occur frequently in ICU patients (16%), irrespective of COVID-19 infection. Expand
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The role of IFN-I signaling in infectious and non-infectious diseases of humans is summarized and the precautionary measures to be considered are highlighted before administering IFn-I to COVID-19 patients having other co-existing disorders. Expand
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It is concluded that type 1 interferon responses in patients with SCD may contribute to the variable COVID-19 responses reported in prior studies. Expand
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Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients
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The detection and quantification of circulating autoantibodies against type I interferon immunity in a cohort of severe COVID-19 patients confirmed the detrimental role of these Abs on the antiviral response, and support the use of recombinant type I IFNs not targeted by the auto-Abs in patients with an impaired IFN-I response. Expand
Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome
COVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction areExpand
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Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
TLDR
The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001. Expand
Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
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The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Expand
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A 28-IFN response gene scoring system is developed to calculate either a standardized or geomean score by customizing a NanoString assay to quantify the expression of putative IRGs and showed high reproducibility and low intra- and interassay variability. Expand
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Anti-Interferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1
TLDR
These apparently spontaneous autoantibody responses to IFNs, particularly IFN-α and IFn-ω, segregate like a recessive trait; their high “penetrance” is especially remarkable for such a variable condition. Expand
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It is postulated that acquired defects in macrophage activation by IFN-gamma may cause a similar immunological phenotype and thus explain the occurrence of disseminated intracellular infections in some patients without identifiable immune deficiency. Expand
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TLDR
Arguments will be presented to support the hypothesis that the major role of IFN is, after all, in antiviral defense, and the use of type I IFN in the treatment of patients with viral and neoplastic diseases and even diseases of varied and unknown etiology is discussed. Expand
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