1932

Abstract

Infection with SARS-CoV-2 results in clinical outcomes ranging from silent or benign infection in most individuals to critical pneumonia and death in a few. Genetic studies in patients have established that critical cases can result from inborn errors of TLR3- or TLR7-dependent type I interferon immunity, or from preexisting autoantibodies neutralizing primarily IFN-α and/or IFN-ω. These findings are consistent with virological studies showing that multiple SARS-CoV-2 proteins interfere with pathways of induction of, or response to, type I interferons. They are also congruent with cellular studies and mouse models that found that type I interferons can limit SARS-CoV-2 replication in vitro and in vivo, while their absence or diminution unleashes viral growth. Collectively, these findings point to insufficient type I interferon during the first days of infection as a general mechanism underlying critical COVID-19 pneumonia, with implications for treatment and directions for future research.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-101921-050835
2023-04-26
2024-04-21
Loading full text...

Full text loading...

/deliver/fulltext/immunol/41/1/annurev-immunol-101921-050835.html?itemId=/content/journals/10.1146/annurev-immunol-101921-050835&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Zhu N, Zhang D, Wang W, Li X, Yang B et al. 2020. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382:727–33
    [Google Scholar]
  2. 2.
    World Health Organ 2021. Living guidance for clinical management of COVID-19 Ver. 3. Living Guid. World Health Organ. Geneva: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
  3. 3.
    Pei S, Yamana TK, Kandula S, Galanti M, Shaman J. 2021. Burden and characteristics of COVID-19 in the United States during 2020. Nature 598:338–41
    [Google Scholar]
  4. 4.
    O'Driscoll M, Ribeiro Dos Santos G, Wang L, Cummings DAT, Azman AS et al. 2021. Age-specific mortality and immunity patterns of SARS-CoV-2. Nature 590:140–45
    [Google Scholar]
  5. 5.
    Sancho-Shimizu V, Brodin P, Cobat A, Biggs CM, Toubiana J et al. 2021. SARS-CoV-2-related MIS-C: a key to the viral and genetic causes of Kawasaki disease?. J. Exp. Med. 218:6e20210446
    [Google Scholar]
  6. 6.
    Arkin LM, Moon JJ, Tran JM, Asgari S, O'Farrelly C et al. 2021. From your nose to your toes: a review of severe acute respiratory syndrome coronavirus 2 pandemic-associated pernio. J. Investig. Dermatol. 141:2791–96
    [Google Scholar]
  7. 7.
    Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C et al. 2021. Post-acute COVID-19 syndrome. Nat. Med. 27:601–15
    [Google Scholar]
  8. 8.
    Koelle K, Martin MA, Antia R, Lopman B, Dean NE. 2022. The changing epidemiology of SARS-CoV-2. Science 375:1116–21
    [Google Scholar]
  9. 9.
    Barouch DH. 2022. Covid-19 vaccines—immunity, variants, boosters. N. Engl. J. Med. 387:1011–20
    [Google Scholar]
  10. 10.
    World Health Organ 2022. Therapeutics and COVID-19: living guideline Ver. 12. Living Guidel. World Health Organ Geneva: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
  11. 11.
    Casanova JL, Abel L. 2022. From rare disorders of immunity to common determinants of infection: following the mechanistic thread. Cell 185:3086–103
    [Google Scholar]
  12. 12.
    Casanova JL, Su HC, Effort CHG. 2020. A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection. Cell 181:1194–99
    [Google Scholar]
  13. 13.
    Andreakos E, Abel L, Vinh DC, Kaja E, Drolet BA et al. 2022. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection. Nat. Immunol. 23:159–64
    [Google Scholar]
  14. 14.
    Lee D, Le Pen J, Yatim A, Dong B, Aquino Y et al. 2022. Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children. Science 20:eabo3627
    [Google Scholar]
  15. 15.
    Isaacs A, Lindenmann J. 1957. Virus interference. I. The interferon. Proc. R. Soc. Lond. B. 147:258–67
    [Google Scholar]
  16. 16.
    Hoffmann HH, Schneider WM, Rice CM. 2015. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol 36:124–38
    [Google Scholar]
  17. 17.
    Lazear HM, Schoggins JW, Diamond MS. 2019. Shared and distinct functions of type I and type III interferons. Immunity 50:907–23
    [Google Scholar]
  18. 18.
    Mesev EV, LeDesma RA, Ploss A. 2019. Decoding type I and III interferon signalling during viral infection. Nat. Microbiol. 4:914–24
    [Google Scholar]
  19. 19.
    Stanifer ML, Pervolaraki K, Boulant S. 2019. Differential regulation of type I and type III interferon signaling. Int. J. Mol. Sci. 20:61445
    [Google Scholar]
  20. 20.
    Teijaro JR. 2016. Type I interferons in viral control and immune regulation. Curr. Opin. Virol. 16:31–40
    [Google Scholar]
  21. 21.
    Stanifer ML, Guo C, Doldan P, Boulant S. 2020. Importance of type I and III interferons at respiratory and intestinal barrier surfaces. Front. Immunol. 11:608645
    [Google Scholar]
  22. 22.
    Nathan CF, Murray HW, Wiebe ME, Rubin BY. 1983. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J. Exp. Med. 158:670–89
    [Google Scholar]
  23. 23.
    Matz KM, Guzman RM, Goodman AG. 2019. The role of nucleic acid sensing in controlling microbial and autoimmune disorders. Int. Rev. Cell Mol. Biol. 345:35–136
    [Google Scholar]
  24. 24.
    Tan X, Sun L, Chen J, Chen ZJ 2018. Detection of microbial infections through innate immune sensing of nucleic acids. Annu. Rev. Microbiol. 72:447–78
    [Google Scholar]
  25. 25.
    Margolis SR, Wilson SC, Vance RE. 2017. Evolutionary origins of cGAS-STING signaling. Trends Immunol 38:733–43
    [Google Scholar]
  26. 26.
    Jefferies CA. 2019. Regulating IRFs in IFN driven disease. Front. Immunol. 10:325
    [Google Scholar]
  27. 27.
    Crow YJ, Stetson DB. 2022. The type I interferonopathies: 10 years on. Nat. Rev. Immunol. 22:471–83
    [Google Scholar]
  28. 28.
    Schoggins JW. 2019. Interferon-stimulated genes: What do they all do?. Annu. Rev. Virol. 6:567–84
    [Google Scholar]
  29. 29.
    Schneider WM, Chevillotte MD, Rice CM. 2014. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32:513–45
    [Google Scholar]
  30. 30.
    Schreiber G. 2017. The molecular basis for differential type I interferon signaling. J. Biol. Chem. 292:7285–94
    [Google Scholar]
  31. 31.
    de Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA et al. 2013. Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1. Nat. Immunol. 14:901–7
    [Google Scholar]
  32. 32.
    Francois-Newton V, Magno de Freitas Almeida G, Payelle-Brogard B, Monneron D, Pichard-Garcia L et al. 2011. USP18-based negative feedback control is induced by type I and type III interferons and specifically inactivates interferon alpha response. PLOS ONE 6:e22200
    [Google Scholar]
  33. 33.
    Stifter SA, Matthews AY, Mangan NE, Fung KY, Drew A et al. 2018. Defining the distinct, intrinsic properties of the novel type I interferon, IFN. J. Biol. Chem. 293:3168–79
    [Google Scholar]
  34. 34.
    Harris BD, Schreiter J, Chevrier M, Jordan JL, Walter MR. 2018. Human interferon- and interferon-kappa exhibit low potency and low affinity for cell-surface IFNAR and the poxvirus antagonist B18R. J. Biol. Chem. 293:16057–68
    [Google Scholar]
  35. 35.
    Wells AI, Coyne CB. 2018. Type III interferons in antiviral defenses at barrier surfaces. Trends Immunol 39:848–58
    [Google Scholar]
  36. 36.
    Okabayashi T, Kojima T, Masaki T, Yokota S, Imaizumi T et al. 2011. Type-III interferon, not type-I, is the predominant interferon induced by respiratory viruses in nasal epithelial cells. Virus Res 160:360–66
    [Google Scholar]
  37. 37.
    Mahlakoiv T, Hernandez P, Gronke K, Diefenbach A, Staeheli P. 2015. Leukocyte-derived IFN-alpha/beta and epithelial IFN-lambda constitute a compartmentalized mucosal defense system that restricts enteric virus infections. PLOS Pathog. 11:e1004782
    [Google Scholar]
  38. 38.
    Klinkhammer J, Schnepf D, Ye L, Schwaderlapp M, Gad HH et al. 2018. IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission. eLife 7:e33354
    [Google Scholar]
  39. 39.
    Meuwissen ME, Schot R, Buta S, Oudesluijs G, Tinschert S et al. 2016. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J. Exp. Med. 213:1163–74
    [Google Scholar]
  40. 40.
    Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O et al. 2012. Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency. Science 337:1684–88
    [Google Scholar]
  41. 41.
    Spence JS, He R, Hoffmann HH, Das T, Thinon E et al. 2019. IFITM3 directly engages and shuttles incoming virus particles to lysosomes. Nat. Chem. Biol. 15:259–68
    [Google Scholar]
  42. 42.
    Haller O, Staeheli P, Schwemmle M, Kochs G. 2015. Mx GTPases: dynamin-like antiviral machines of innate immunity. Trends Microbiol 23:154–63
    [Google Scholar]
  43. 43.
    Gizzi AS, Grove TL, Arnold JJ, Jose J, Jangra RK et al. 2018. A naturally occurring antiviral ribonucleotide encoded by the human genome. Nature 558:610–14
    [Google Scholar]
  44. 44.
    Kristiansen H, Gad HH, Eskildsen-Larsen S, Despres P, Hartmann R. 2011. The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities. J. Interferon Cytokine Res. 31:41–47
    [Google Scholar]
  45. 45.
    Chen Y, Graf L, Chen T, Liao Q, Bai T et al. 2021. Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus. Science 373:918–22
    [Google Scholar]
  46. 46.
    McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. 2015. Type I interferons in infectious disease. Nat. Rev. Immunol. 15:87–103
    [Google Scholar]
  47. 47.
    Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M et al. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191:1777–88
    [Google Scholar]
  48. 48.
    Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C et al. 2006. Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J. Immunol. 176:2074–78
    [Google Scholar]
  49. 49.
    Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF. 2005. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J. Immunol. 174:4465–69
    [Google Scholar]
  50. 50.
    Biron CA, Sonnenfeld G, Welsh RM. 1984. Interferon induces natural killer cell blastogenesis in vivo. J. Leukoc. Biol. 35:31–37
    [Google Scholar]
  51. 51.
    Boukhaled GM, Harding S, Brooks DG. 2021. Opposing roles of type I interferons in cancer immunity. Annu. Rev. Pathol. 16:167–98
    [Google Scholar]
  52. 52.
    Lasfar A, Gogas H, Zloza A, Kaufman HL, Kirkwood JM. 2016. IFN-lambda cancer immunotherapy: new kid on the block. Immunotherapy 8:877–88
    [Google Scholar]
  53. 53.
    Felgenhauer U, Schoen A, Gad HH, Hartmann R, Schaubmar AR et al. 2020. Inhibition of SARS-CoV-2 by type I and type III interferons. J. Biol. Chem. 295:13958–64
    [Google Scholar]
  54. 54.
    Lokugamage KG, Hage A, de Vries M, Valero-Jimenez AM, Schindewolf C et al. 2020. Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. J. Virol. 94:23e01410–20
    [Google Scholar]
  55. 55.
    Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S et al. 2020. Critical role of type III interferon in controlling SARS-CoV-2 infection in human intestinal epithelial cells. Cell Rep 32:107863
    [Google Scholar]
  56. 56.
    Clementz MA, Chen Z, Banach BS, Wang Y, Sun L et al. 2010. Deubiquitinating and interferon antagonism activities of coronavirus papain-like proteases. J. Virol. 84:4619–29
    [Google Scholar]
  57. 57.
    Kopecky-Bromberg SA, Martinez-Sobrido L, Frieman M, Baric RA, Palese P. 2007. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J. Virol. 81:548–57
    [Google Scholar]
  58. 58.
    Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. 2007. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J. Virol. 81:9812–24
    [Google Scholar]
  59. 59.
    Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P et al. 2020. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. PNAS 117:28344–54
    [Google Scholar]
  60. 60.
    Lei X, Dong X, Ma R, Wang W, Xiao X et al. 2020. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11:3810
    [Google Scholar]
  61. 61.
    Schroeder S, Pott F, Niemeyer D, Veith T, Richter A et al. 2021. Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics. Lancet Microbe 2:e210–18
    [Google Scholar]
  62. 62.
    Corey L, Beyrer C, Cohen MS, Michael NL, Bedford T, Rolland M 2021. SARS-CoV-2 variants in patients with immunosuppression. N. Engl. J. Med. 385:562–66
    [Google Scholar]
  63. 63.
    Avanzato VA, Matson MJ, Seifert SN, Pryce R, Williamson BN et al. 2020. Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell 183:1901–12.e9
    [Google Scholar]
  64. 64.
    Choi B, Choudhary MC, Regan J, Sparks JA, Padera RF et al. 2020. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N. Engl. J. Med. 383:2291–93
    [Google Scholar]
  65. 65.
    Truong TT, Ryutov A, Pandey U, Yee R, Goldberg L et al. 2021. Increased viral variants in children and young adults with impaired humoral immunity and persistent SARS-CoV-2 infection: a consecutive case series. EBioMedicine 67:103355
    [Google Scholar]
  66. 66.
    Kemp SA, Collier DA, Datir RP, Ferreira I, Gayed S et al. 2021. SARS-CoV-2 evolution during treatment of chronic infection. Nature 592:277–82
    [Google Scholar]
  67. 67.
    Munoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX et al. 2020. Animal models for COVID-19. Nature 586:509–15
    [Google Scholar]
  68. 68.
    Casanova JL, Abel L. 2004. The human model: a genetic dissection of immunity to infection in natural conditions. Nat. Rev. Immunol. 4:55–66
    [Google Scholar]
  69. 69.
    Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J et al. 2016. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 19:181–93
    [Google Scholar]
  70. 70.
    Lowery SA, Sariol A, Perlman S. 2021. Innate immune and inflammatory responses to SARS-CoV-2: implications for COVID-19. Cell Host Microbe 29:1052–62
    [Google Scholar]
  71. 71.
    Sun J, Zhuang Z, Zheng J, Li K, Wong RL et al. 2020. Generation of a broadly useful model for COVID-19 pathogenesis, vaccination, and treatment. Cell 182:734–43.e5
    [Google Scholar]
  72. 72.
    Hassan AO, Case JB, Winkler ES, Thackray LB, Kafai NM et al. 2020. A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell 182:744–53.e4
    [Google Scholar]
  73. 73.
    Israelow B, Song E, Mao T, Lu P, Meir A et al. 2020. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. J. Exp. Med. 217:12e20201241
    [Google Scholar]
  74. 74.
    Robertson SJ, Bedard O, McNally KL, Lewis M, Clancy C et al. 2022. Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation and cytokine responses in COVID-19. bioRxiv 2021.09.17.460664, Feb. 24
  75. 75.
    Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J et al. 2022. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 606:585–93
    [Google Scholar]
  76. 76.
    Trouillet-Assant S, Viel S, Gaymard A, Pons S, Richard JC et al. 2020. Type I IFN immunoprofiling in COVID-19 patients. J. Allergy Clin. Immunol. 146:206–8.e2
    [Google Scholar]
  77. 77.
    Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J et al. 2020. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369:718–24
    [Google Scholar]
  78. 78.
    Lim HK, Huang SXL, Chen J, Kerner G, Gilliaux O et al. 2019. Severe influenza pneumonitis in children with inherited TLR3 deficiency. J. Exp. Med. 216:2038–56
    [Google Scholar]
  79. 79.
    Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M et al. 2020. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370:6515eabd4570
    [Google Scholar]
  80. 80.
    Abolhassani H, Landegren N, Bastard P, Materna M, Modaresi M et al. 2022. Inherited IFNAR1 deficiency in a child with both critical COVID-19 pneumonia and multisystem inflammatory syndrome. J. Clin. Immunol. 42:471–83
    [Google Scholar]
  81. 81.
    Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M et al. 2021. X-linked recessive TLR7 deficiency in ∼1% of men under 60 years old with life-threatening COVID-19. Sci. Immunol. 6:62eabl4348
    [Google Scholar]
  82. 82.
    Zhang Q, Matuozzo D, Le Pen J, Lee D, Moens L et al. 2022. Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia. J. Exp. Med. 219:8e20220131
    [Google Scholar]
  83. 83.
    Campbell TM, Liu Z, Zhang Q, Moncada-Velez M, Covill LE et al. 2022. Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency. J. Exp. Med. 219:7e20220202 Erratum. 2022. J. Exp. Med. 219(12):e2022020210282022c
    [Google Scholar]
  84. 84.
    Schmidt A, Peters S, Knaus A, Sabir H, Hamsen F et al. 2021. TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19. npj Genom. Med. 6:55
    [Google Scholar]
  85. 85.
    Matuozzo D, Talouarn E, Marchal A, Manry J, Seeleuthner Y et al. 2022. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. medRxiv 2022.10.22.22281221, Oct. 25
  86. 86.
    Levy R, Bastard P, Lanternier F, Lecuit M, Zhang SY, Casanova JL. 2021. IFN-α2a therapy in two patients with inborn errors of TLR3 and IRF3 infected with SARS-CoV-2. J. Clin. Immunol. 41:26–27
    [Google Scholar]
  87. 87.
    van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T et al. 2020. Presence of genetic variants among young men with severe COVID-19. JAMA 324:663–73
    [Google Scholar]
  88. 88.
    Fallerini C, Daga S, Mantovani S, Benetti E, Picchiotti N et al. 2021. Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study. eLife 10:e67569
    [Google Scholar]
  89. 89.
    Onodi F, Bonnet-Madin L, Meertens L, Karpf L, Poirot J et al. 2021. SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4. J. Exp. Med. 218:4e20201387
    [Google Scholar]
  90. 90.
    García-García A, Pérez de Diego R, Flores C, Zhang Q, Rinchai D et al. 2022. Inherited MyD88 and IRAK-4 deficiencies confer a predisposition to hypoxemic COVID-19 pneumonia. J. Exp. Med. In press
    [Google Scholar]
  91. 91.
    Duncan CJA, Randall RE, Hambleton S. 2021. Genetic lesions of type I interferon signalling in human antiviral immunity. Trends Genet. 37:46–58
    [Google Scholar]
  92. 92.
    Meyts I, Casanova JL. 2021. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway. Eur. J. Immunol. 51:1039–61
    [Google Scholar]
  93. 93.
    Yazdani R, Moazzami B, Madani SP, Behniafard N, Azizi G et al. 2019. Candidiasis associated with very early onset inflammatory bowel disease: first IL10RB deficient case from the National Iranian Registry and review of the literature. Clin. Immunol. 205:35–42
    [Google Scholar]
  94. 94.
    Bastard P, Hsiao KC, Zhang Q, Choin J, Best E et al. 2022. A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes. J. Exp. Med. 219:6e20220028
    [Google Scholar]
  95. 95.
    Hernandez N, Bucciol G, Moens L, Le Pen J, Shahrooei M et al. 2019. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines. J. Exp. Med. 216:2057–70
    [Google Scholar]
  96. 96.
    Meyts I. 2022. Null IFNAR1 and IFNAR2 alleles are surprisingly common in the Pacific and Arctic. J. Exp. Med. 219:6e20220491
    [Google Scholar]
  97. 97.
    COVID-19 Host Genet. Initiat 2021. Mapping the human genetic architecture of COVID-19. Nature 600:472–77
    [Google Scholar]
  98. 98.
    Kousathanas A, Pairo-Castineira E, Rawlik K, Stuckey A, Odhams CA et al. 2022. Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature 607:97–103
    [Google Scholar]
  99. 99.
    Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K et al. 2021. Genetic mechanisms of critical illness in COVID-19. Nature 591:92–98
    [Google Scholar]
  100. 100.
    Severe Covid-19 GWAS Group, Ellinghaus D, Degenhardt F, Bujanda L, Buti M et al. 2020. Genomewide association study of severe Covid-19 with respiratory failure. N. Engl. J. Med. 383:1522–34
    [Google Scholar]
  101. 101.
    Nakanishi T, Pigazzini S, Degenhardt F, Cordioli M, Butler-Laporte G et al. 2021. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality. J. Clin. Investig. 131:23e152386
    [Google Scholar]
  102. 102.
    Banday AR, Stanifer ML, Florez-Vargas O, Onabajo OO, Papenberg BW et al. 2022. Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries. Nat. Genet. 54:81103–16
    [Google Scholar]
  103. 103.
    Zeberg H, Paabo S. 2021. A genomic region associated with protection against severe COVID-19 is inherited from Neandertals. PNAS 118:9e2026309118
    [Google Scholar]
  104. 104.
    Soveg FW, Schwerk J, Gokhale NS, Cerosaletti K, Smith JR et al. 2021. Endomembrane targeting of human OAS1 p46 augments antiviral activity. eLife 10:e71047
    [Google Scholar]
  105. 105.
    Puel A, Bastard P, Bustamante J, Casanova JL. 2022. Human autoantibodies underlying infectious diseases. J. Exp. Med. 219:4e20211387
    [Google Scholar]
  106. 106.
    Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q et al. 2021. Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths. Sci. Immunol. 6:62eabl4340
    [Google Scholar]
  107. 107.
    Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH et al. 2020. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370:6515eabd4585
    [Google Scholar]
  108. 108.
    Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J et al. 2022. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. PNAS 119:e2200413119
    [Google Scholar]
  109. 109.
    Zhang Q, Bastard P, COVID Hum. Genet. Effort, Cobat A, Casanova JL 2022. Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature 603:587–98
    [Google Scholar]
  110. 110.
    Pozzetto B, Mogensen KE, Tovey MG, Gresser I. 1984. Characteristics of autoantibodies to human interferon in a patient with varicella-zoster disease. J. Infect. Dis. 150:707–13
    [Google Scholar]
  111. 111.
    Lopez J, Mommert M, Mouton W, Pizzorno A, Brengel-Pesce K et al. 2021. Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs. J. Exp. Med. 218:10e20211211 Erratum. 2021. J. Exp. Med. 218(10):e2021121108132021c
    [Google Scholar]
  112. 112.
    van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T et al. 2021. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Sci. Transl. Med. 13:eabh2624
    [Google Scholar]
  113. 113.
    Savvateeva E, Filippova M, Valuev-Elliston V, Nuralieva N, Yukina M et al. 2021. Microarray-based detection of antibodies against SARS-CoV-2 proteins, common respiratory viruses and type I interferons. Viruses 13:122553
    [Google Scholar]
  114. 114.
    Eto S, Nukui Y, Tsumura M, Nakagama Y, Kashimada K et al. 2022. Neutralizing type I interferon autoantibodies in Japanese patients with severe COVID-19. J. Clin. Immunol. 42:71360–70
    [Google Scholar]
  115. 115.
    Busnadiego I, Abela IA, Frey PM, Hofmaenner DA, Scheier TC et al. 2022. Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease. PLOS Biol 20:e3001709
    [Google Scholar]
  116. 116.
    Lamacchia G, Mazzoni A, Spinicci M, Vanni A, Salvati L et al. 2022. Clinical and immunological features of SARS-CoV-2 breakthrough infections in vaccinated individuals requiring hospitalization. J. Clin. Immunol. 42:71379–91
    [Google Scholar]
  117. 117.
    Meisel C, Akbil B, Meyer T, Lankes E, Corman VM et al. 2021. Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1. J. Clin. Investig. 131:14e150867
    [Google Scholar]
  118. 118.
    Soltani-Zangbar MS, Parhizkar F, Ghaedi E, Tarbiat A, Motavalli R et al. 2022. A comprehensive evaluation of the immune system response and type-I interferon signaling pathway in hospitalized COVID-19 patients. Cell Commun. Signal. 20:106
    [Google Scholar]
  119. 119.
    Simula ER, Manca MA, Noli M, Jasemi S, Ruberto S et al. 2022. Increased presence of antibodies against type I interferons and human endogenous retrovirus W in intensive care unit COVID-19 patients. Microbiol. Spectr. 10:4e0128022
    [Google Scholar]
  120. 120.
    Raadsen MP, Gharbharan A, Jordans CCE, Mykytyn AZ, Lamers MM et al. 2022. Interferon-α2 auto-antibodies in convalescent plasma therapy for COVID-19. J. Clin. Immunol. 42:232–39
    [Google Scholar]
  121. 121.
    Frasca F, Scordio M, Santinelli L, Gabriele L, Gandini O et al. 2022. Anti-IFN-alpha/-omega neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity. Eur. J. Immunol. 52:1120–28
    [Google Scholar]
  122. 122.
    Carapito R, Li R, Helms J, Carapito C, Gujja S et al. 2022. Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort. Sci. Transl. Med. 14:eabj7521
    [Google Scholar]
  123. 123.
    Akbil B, Meyer T, Stubbemann P, Thibeault C, Staudacher O et al. 2022. Early and rapid identification of COVID-19 patients with neutralizing type I interferon auto-antibodies. J. Clin. Immunol. 42:61111–29
    [Google Scholar]
  124. 124.
    Ziegler CGK, Miao VN, Owings AH, Navia AW, Tang Y et al. 2021. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell 184:4713–33.e22
    [Google Scholar]
  125. 125.
    Wang EY, Mao T, Klein J, Dai Y, Huck JD et al. 2021. Diverse functional autoantibodies in patients with COVID-19. Nature 595:283–88
    [Google Scholar]
  126. 126.
    Vazquez SE, Bastard P, Kelly K, Gervais A, Norris PJ et al. 2021. Neutralizing autoantibodies to type I interferons in COVID-19 convalescent donor plasma. J. Clin. Immunol. 41:1169–71
    [Google Scholar]
  127. 127.
    Troya J, Bastard P, Planas-Serra L, Ryan P, Ruiz M et al. 2021. Neutralizing autoantibodies to type I IFNs in >10% of patients with severe COVID-19 pneumonia hospitalized in Madrid, Spain. J. Clin. Immunol. 41:914–22
    [Google Scholar]
  128. 128.
    Solanich X, Rigo-Bonnin R, Gumucio VD, Bastard P, Rosain J et al. 2021. Pre-existing autoantibodies neutralizing high concentrations of type I interferons in almost 10% of COVID-19 patients admitted to intensive care in Barcelona. J. Clin. Immunol. 41:1733–44
    [Google Scholar]
  129. 129.
    Lemarquis A, Campbell T, Aranda-Guillen M, Hennings V, Brodin P et al. 2021. Severe COVID-19 in an APS1 patient with interferon autoantibodies treated with plasmapheresis. J. Allergy Clin. Immunol. 148:96–98
    [Google Scholar]
  130. 130.
    Koning R, Bastard P, Casanova JL, Brouwer MC, van de Beek D; with Amst. U.M.C. COVID-19 Biobank Investig 2021. Autoantibodies against type I interferons are associated with multi-organ failure in COVID-19 patients. Intensive Care Med 47:704–6
    [Google Scholar]
  131. 131.
    Goncalves D, Mezidi M, Bastard P, Perret M, Saker K et al. 2021. Antibodies against type I interferon: detection and association with severe clinical outcome in COVID-19 patients. Clin. Transl. Immunol. 10:e1327
    [Google Scholar]
  132. 132.
    Chauvineau-Grenier A, Bastard P, Servajean A, Gervais A, Rosain J et al. 2022. Autoantibodies neutralizing type I interferons in 20% of COVID-19 deaths in a French hospital. J. Clin. Immunol. 42:459–70
    [Google Scholar]
  133. 133.
    Chang SE, Feng A, Meng W, Apostolidis SA, Mack E et al. 2021. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat. Commun. 12:5417
    [Google Scholar]
  134. 134.
    Bastard P, Orlova E, Sozaeva L, Levy R, James A et al. 2021. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J. Exp. Med. 21:7e20210554
    [Google Scholar]
  135. 135.
    Acosta-Ampudia Y, Monsalve DM, Rojas M, Rodriguez Y, Gallo JE et al. 2021. COVID-19 convalescent plasma composition and immunological effects in severe patients. J Autoimmun 118:102598
    [Google Scholar]
  136. 136.
    Abers MS, Rosen LB, Delmonte OM, Shaw E, Bastard P et al. 2021. Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19. Immunol. Cell Biol. 99:917–21
    [Google Scholar]
  137. 137.
    Mathian A, Breillat P, Dorgham K, Bastard P, Charre C et al. 2022. Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α. Ann. Rheum. Dis. 81:1695–703
    [Google Scholar]
  138. 138.
    Bastard P, Vazquez S, Liu J, Laurie MT, Wang CY et al. 2022. Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs. Sci. Immunol 14:eabp8966
    [Google Scholar]
  139. 139.
    Shaw ER, Rosen LB, Cheng A, Dobbs K, Delmonte OM et al. 2022. Temporal dynamics of anti-type 1 interferon autoantibodies in patients with coronavirus disease 2019. Clin. Infect. Dis. 75:1e1192–94
    [Google Scholar]
  140. 140.
    Steels S, Van Elslande J, Leuven C-SG, De Munter P, Bossuyt X. 2022. Transient increase of pre-existing anti-IFN-α2 antibodies induced by SARS-CoV-2 infection. J. Clin. Immunol. 42:742–45
    [Google Scholar]
  141. 141.
    Walter JE, Rosen LB, Csomos K, Rosenberg JM, Mathew D et al. 2015. Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency. J. Clin. Investig. 125:4135–48
    [Google Scholar]
  142. 142.
    Rosenberg JM, Maccari ME, Barzaghi F, Allenspach EJ, Pignata C et al. 2018. Neutralizing anti-cytokine autoantibodies against interferon-alpha in immunodysregulation polyendocrinopathy enteropathy X-linked. Front. Immunol. 9:544
    [Google Scholar]
  143. 143.
    Levin M. 2006. Anti-interferon auto-antibodies in autoimmune polyendocrinopathy syndrome type 1. PLOS Med 3:e292
    [Google Scholar]
  144. 144.
    Cheng MH, Fan U, Grewal N, Barnes M, Mehta A et al. 2010. Acquired autoimmune polyglandular syndrome, thymoma, and an AIRE defect. N. Engl. J. Med. 362:764–66
    [Google Scholar]
  145. 145.
    Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T et al. 2021. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J. Exp. Med. 218:4e20202486
    [Google Scholar]
  146. 146.
    Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A et al. 2022. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J. Exp. Med. 219:11e20220514
    [Google Scholar]
  147. 147.
    Oo A, Zandi K, Shepard C, Bassit LC, Musall K et al. 2022. Elimination of Aicardi-Goutières syndrome protein SAMHD1 activates cellular innate immunity and suppresses SARS-CoV-2 replication. J. Biol. Chem. 298:101635
    [Google Scholar]
  148. 148.
    Hubiche T, Cardot-Leccia N, Le Duff F, Seitz-Polski B, Giordana P et al. 2021. Clinical, laboratory, and interferon-alpha response characteristics of patients with chilblain-like lesions during the COVID-19 pandemic. JAMA Dermatol 157:202–6
    [Google Scholar]
  149. 149.
    Colmenero I, Santonja C, Alonso-Riano M, Andina D, Rodriguez-Peralto JL et al. 2020. Chilblains and COVID-19: why SARS-CoV-2 endothelial infection is questioned; reply from the authors. Br. J. Dermatol. 183:1153–54
    [Google Scholar]
  150. 150.
    Gehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C et al. 2022. Lack of association between pandemic chilblains and SARS-CoV-2 infection. PNAS 119:9e2122090119
    [Google Scholar]
  151. 151.
    Wang ML, Chan MP. 2018. Comparative analysis of chilblain lupus erythematosus and idiopathic perniosis: histopathologic features and immunohistochemistry for CD123 and CD30. Am. J. Dermatopathol. 40:265–71
    [Google Scholar]
  152. 152.
    Frumholtz L, Bouaziz JD, Battistella M, Hadjadj J, Chocron R et al. 2021. Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak. Br. J. Dermatol. 185:1176–85
    [Google Scholar]
  153. 153.
    Manzano GS, Woods JK, Amato AA. 2020. Covid-19-associated myopathy caused by type I interferonopathy. N. Engl. J. Med. 383:2389–90
    [Google Scholar]
  154. 154.
    Okada Y, Izumi R, Hosaka T, Watanabe S, Shijo T et al. 2022. Anti-NXP2 antibody-positive dermatomyositis developed after COVID-19 manifesting as type I interferonopathy. Rheumatology 61:e90–92
    [Google Scholar]
  155. 155.
    Hung IF, Lung KC, Tso EY, Liu R, Chung TW et al. 2020. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 395:1695–704
    [Google Scholar]
  156. 156.
    Monk PD, Marsden RJ, Tear VJ, Brookes J, Batten TN et al. 2021. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir. Med. 9:196–206
    [Google Scholar]
  157. 157.
    Davoudi-Monfared E, Rahmani H, Khalili H, Hajiabdolbaghi M, Salehi M et al. 2020. A randomized clinical trial of the efficacy and safety of interferon beta-1a in treatment of severe COVID-19. Antimicrob. Agents Chemother. 64:9e01061–20
    [Google Scholar]
  158. 158.
    Rahmani H, Davoudi-Monfared E, Nourian A, Khalili H, Hajizadeh N et al. 2020. Interferon beta-1b in treatment of severe COVID-19: a randomized clinical trial. Int. Immunopharmacol. 88:106903
    [Google Scholar]
  159. 159.
    WHO Solidarity Trial Consortium 2021. Repurposed antiviral drugs for Covid-19—interim WHO solidarity trial results. N. Engl. J. Med. 384:497–511
    [Google Scholar]
  160. 160.
    Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D et al. 2021. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-beta-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin. Microbiol. Infect. 27:1826–37
    [Google Scholar]
  161. 161.
    Kalil AC, Mehta AK, Patterson TF, Erdmann N, Gomez CA et al. 2021. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir. Med. 9:1365–76
    [Google Scholar]
  162. 162.
    Beigel JH. 2021. What is the role of remdesivir in patients with COVID-19?. Curr. Opin. Crit. Care 27:487–92
    [Google Scholar]
  163. 163.
    Zhang Q, Bastard P, Bolze A, Jouanguy E, Zhang SY et al. 2020. Life-threatening COVID-19: defective interferons unleash excessive inflammation. Med 1:14–20
    [Google Scholar]
  164. 164.
    Zhang Z, Guo L, Huang L, Zhang C, Luo R et al. 2021. Distinct disease severity between children and older adults with coronavirus disease 2019 (COVID-19): impacts of ACE2 expression, distribution, and lung progenitor cells. Clin. Infect. Dis. 73:e4154–65
    [Google Scholar]
  165. 165.
    Jing Y, Shaheen E, Drake RR, Chen N, Gravenstein S, Deng Y. 2009. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum. Immunol. 70:777–84
    [Google Scholar]
  166. 166.
    Loske J, Rohmel J, Lukassen S, Stricker S, Magalhaes VG et al. 2022. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat. Biotechnol. 40:319–24
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-101921-050835
Loading
/content/journals/10.1146/annurev-immunol-101921-050835
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error