Коронавирусная болезнь 2019 (COVID-19) и аутоиммунитет

Пандемия коронавирусной болезни 2019 (coronavirus disease, COVID-19), этиологически связанной с вирусом SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), привлекла внимание медицинского сообщества к новым клиническим и фундаментальным проблемам иммунопатологии заболеваний человека. В течение года, прошедшего с начала пандемии, было проведено беспрецедентное число клинических и фундаментальных исследований, посвященных проблемам эпидемиологии, вирусологии, иммунологии и молекулярной биологии, клинического течения, полиморфизма и фармакотерапии COVID-19, объединивших ученых и врачей практически всех биологических и медицинских специальностей. Эти усилия увенчались созданием нескольких типов вакцин против инфекции SARS-CoV-2 и в целом разработкой более рациональных подходов к ведению пациентов. 2020 год является юбилейным, поскольку именно 70 лет назад (в 1950 году) Т. Рейхштейн, Э. Кендалл и Ф. Хенч были удостоены Нобелевской премии, за «открытия, касающиеся гормонов коры надпочечников, структуры и биологических эффектов». Не менее важное значение имеют исследования, касающиеся применения генно-инженерных биологических препаратов и «таргетных» противовоспалительных препаратов, модулирующих внутриклеточную сигнализацию цитокинов, которые в течение последних 20 лет специально разрабатывались для лечения иммуновоспалительных ревматических заболеваний (ИВРЗ). В процессе детального анализа спектра клинических проявлений и иммунопатологических нарушений при COVID-19 стало очевидным, что инфекция SARS-CoV-2 сопровождается развитием широкого спектра экстрапульмональных клинических и лабораторных нарушений, некоторые из которых характерны для ИВРЗ и других аутоиммунных и аутовоспалительных заболеваний человека. Все вместе это послужило основанием для «репозиционирования» (drug repurposing) и применения по незарегистрированным показаниям (off-label) при COVID-19 противовоспалительных препаратов, ранее специально разработанных для лечения ИВРЗ. В статье обсуждаются перспективы лечения COVID-19 с использованием глюкокортикоидов, генно-инженерных биологических препаратов, ингибиторов JAK и других препаратов, блокирующих эффекты провоспалительных цитокинов.

1. Насонов ЕЛ. Коронавирусная болезнь 2019 (COVID-19): размышления ревматолога. Научно-практическая ревматология. 2020;58(2):123–132. doi: 10.14412/1995-4484-2020-123-132

2. Osier F, Ting JPY, Fraser J, Lambrecht BN, Romano M, Gazzinelli RT, et al. The global response to the COVID-19 pandemic: how have immunology societies contributed? Nat Rev Immunol. 2020;20(10):594–602. doi: 10.1038/s41577-020-00428-4

3. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20(10):615–632. doi: 10.1038/s41577-020-00434-6

4. Bhimra A, Morgan RL, Shumaker AM, Lavergne V, Badeb L, et al. Infectious Disease Society of American Guidelines on the Treatment and Management of Patients with COVID-19. URL: www.idsociety.org/COVID19guidelines (Accessed: 8th January 2021).

5. McInnes IB. COVID-19 and rheumatology: first steps towards a different future? Ann Rheum Dis. 2020;79(5):551–552. doi: 10.1136/annrheumdis-2020-217494

6. Robinson PC, Yazdany J. The COVID-19 Global Rheumatology Alliance: collecting data in a pandemic. Nat Rev Rheumatol. 2020;16(6):293–294. doi: 10.1038/s41584-020-0418-0

7. Yazdany J. COVID-19 in rheumatic diseases: A research agenda. Arthritis Rheumatol. 2020;72(10):1596–1599. doi: 10.1002/art.41447

8. Burmester GR, Bijlsma JWJ, Cutolo M, McInnes IB. Managing rheumatic and musculoskeletal diseases – past, present and future. Nat Rev Rheumatol. 2017;13(7):443–448. doi: 10.1038/nrrheum.2017.95

9. Schett G, Sticherling M, Neurath MF. COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol. 2020;20(5):271–272. doi: 10.1038/s41577-020-0312-7

10. Schett G, Manger B, Simon D, Caporali R. COVID-19 revisiting inflammatory pathways of arthritis. Nat Rev Rheumatol. 2020;16(8):465–470. doi: 10.1038/s41584-020-0451-z

11. Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. doi: 10.1016/j.autrev.2020.102597

12. Rodríguez Y, Novelli L, Rojas M, De Santis M, Acosta-Ampudia Y, et al. Autoinflammatory and autoimmune conditions at the crossroad of COVID-19. J Autoimmun. 2020;114:102506. doi: 10.1016/j.jaut.2020.102506

13. Насонов ЕЛ, Бекетова ТВ, Решетняк ТМ, Лила АМ, Ананьева ЛП, Лисицина ТА и др. Коронавирусная болезнь 2019 (COVID-19) и иммуновоспалительные ревматические заболевания: на перекрестке проблем тромбовоспаления и аутоиммунитета. Научно-практическая ревматология. 2020;58(4):353–367. doi: 10.47360/1995-4484-2020-353-367

14. Raju TN. The Nobel chronicles. 1950: Edward Calvin Kendall (1886–1972); Philip Showalter Hench (1896–1965); and Tadeus Reichstein (1897–1996). Lancet. 1999;353(9161):1370. doi: 10.1016/s0140-6736(05)74374-9

15. Hench PS. The present status of cortisone and ACTH in general medicine. Proc R Soc Med. 1950;43(10):769–773.

16. Cain DW, Cidlowski JA. After 62 years of regulating immunity, dexamethasone meets COVID-19. Nat Rev Immunol. 2020;20(10):587–588. doi: 10.1038/s41577-020-00421-x

17. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175–87. doi: 10.1136/annrheumdis-2017-211555

18. Насонов ЕЛ. Фармакотерапия ревматоидного артрита: новая стратегия, новые мишени. Научно-практическая ревматология. 2017;55(4):409–419. doi: 10.14412/1995-4484-2017-409-419

19. Насонов ЕЛ, Лила АМ. Ингибиция интерлейкина 6 при иммуновоспалительных ревматических заболеваниях: достижения, перспективы и надежды. Научно-практическая ревматология. 2017;55(6):590–599. doi: 10.14412/1995-4484-2017-590-599

20. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16(6):335–345. doi: 10.1038/s41584-020-0419-z

21. Nasonov E, Samsonov M. The role of Interleukin 6 inhibitors in therapy of severe COVID-19. Biomed Pharmacother. 2020;131: 110698. doi: 10.1016/j.biopha.2020.110698

22. McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19(6):102537. doi: 10.1016/j.autrev.2020.102537

23. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2020:1–14. doi: 10.1038/s41579-020-00459-7

24. Zhou T, Su TT, Mudianto T, Wang J. Immune asynchrony in COVID-19 pathogenesis and potential immunotherapies. J Exp Med. 2020;217(10):e20200674. doi: 10.1084/jem.20200674

25. Miossec P. Synergy between cytokines and risk factors in the cytokine storm of COVID-19: Does ongoing use of cytokine inhibitors have a protective effect? Arthritis Rheumatol. 2020;72(12):1963–1966. doi: 10.1002/art.41458

26. Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, et al. Genetic mechanisms of critical illness in Covid-19. Nature. 2020 Dec 11. doi: 10.1038/s41586-020-03065-y

27. Zhou F, Yu T, Du R, Fan G, Liu Y, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395(10229): 1054–1062. doi: 10.1016/S0140-6736(20)30566-3

28. Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, et al. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021;6(1):144455. doi: 10.1172/jci.insight.144455

29. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636– 1643. doi: 10.1038/s41591-020-1051-9

30. Lucas C, Wong P, Klein J, Castro TBR, Silva J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020;584(7821):463–469. doi: 10.1038/s41586-020-2588-y

31. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0

32. Mangalmurti N, Hunter CA. Cytokine storms: Understanding COVID-19. Immunity. 2020;53(1):19–25. doi: 10.1016/j.immuni.2020.06.017

33. Fajgenbaum DC, June CH, Cytokine storm. N Engl J Med. 2020;383:2255-2273. doi: 10.1056/NEJMra2026131

34. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, et al. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol. 2020;72(7):1059–1063. doi: 10.1002/art.41285

35. Remy KE, Mazer M, Striker DA, Ellebedy AH, Walton AH, et al. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020;5(17):e140329. doi: 10.1172/jci.insight.140329

36. Chen X, Zhao B, Qu Y, Chen Y, Xiong J, et al. Detectable serum severe acute respiratory syndrome coronavirus 2 viral load (RNAemia) is closely correlated with drastically elevated interleukin 6 level in critically ill patients with coronavirus disease 2019. Clin Infect Dis. 2020;71(8):1937–1942. doi: 10.1093/cid/ciaa449

37. Bermejo-Martin JF, González-Rivera M, Almansa R, Micheloud D, Tedim AP, et al. Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19. Crit Care. 2020;24(1):691. doi: 10.1186/s13054-020-03398-0

38. Li H, Liu L, Zhang D, Xu J, Dai H, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517– 1520. doi: 10.1016/S0140-6736(20)30920-X

39. Leisman DE, Ronner L, Pinotti R, Taylor MD, Sinha P, et al. Cytokine elevation in severe and critical COVID-19: A rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020;8(12):1233–1244. doi: 10.1016/S2213-2600(20)30404-5

40. Sinha P, Matthay MA, Calfee CS. Is a «cytokine storm» relevant to COVID-19? JAMA Intern Med. 2020;180(9):1152–1154. doi: 10.1001/jamainternmed.2020.3313

41. Каледа МИ, Никишина ИП, Федоров ЕС, Насонов ЕЛ. Коронавирусная болезнь 2019 (COVID-19) у детей: уроки педиатрической ревматологии. Научно-практическая ревматология. 2020;58(5):469–479. doi: 10.47360/1995-4484-2020-469-479

42. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20(8):453–454. doi: 10.1038/s41577-020-0367-5

43. Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection – United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(40):1450–1456. doi: 10.15585/mmwr.mm6940e1

44. Weatherhead JE, Clark E, Vogel TP, Atmar RL, Kulkarni PA. Inflammatory syndromes associated with SARS-CoV-2 infection: Dysregulation of the immune response across the age spectrum. J Clin Invest. 2020;130(12):6194–6197. doi: 10.1172/JCI145301

45. Kingsmore KM, Grammer AC, Lipsky PE. Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases. Nat Rev Rheumatol. 2020;16(1):32–52. doi: 10.1038/s41584-019-0337-0

46. Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev. 2020;19(7):102567. doi: 10.1016/j.autrev.2020.102567

47. Hyrich KL, Machado PM. Rheumatic disease and COVID-19: Epidemiology and outcomes. Nat Rev Rheumatol. 2020. doi: 10.1038/s41584-020-00562-2

48. Sepriano A, Kerschbaumer A, Smolen JS, van der Heijde D, Dougados M, et al. Safety of synthetic and biological DMARDs: A systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):760–770. doi: 10.1136/annrheumdis-2019-216653

49. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430–436. doi: 10.1038/s41586-020-2521-4

50. Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, et al.; COVID-19 Global Rheumatology Alliance. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: Data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020;79(7):859–866. doi: 10.1136/annrheumdis-2020-217871

51. Liu M, Gao Y, Zhang Y, Shi S, Chen Y, Tian J. The association between severe or dead COVID-19 and autoimmune diseases: A systematic review and meta-analysis. J Infect. 2020;81(3):e93–e95. doi: 10.1016/j.jinf.2020.05.065

52. Jethwa H, Sullivan A, Abraham S. COVID-19 and immunomodulatory therapy – Can we use data from previous viral pandemics? J Rheumatol. 2020;47(12):1734–1737. doi: 10.3899/jrheum.200527

53. Peach E, Rutter M, Lanyon P, Grainge MJ, et al. Risk of death among people with rare autoimmune diseases compared to the general population in England during the 2020 COVID-19 pandemic. Rheumatology. 2020. doi: 10.1093/rheumatology/keaa855

54. Isaacs JD, Burmester GR. Smart battles: immunosuppression versus immunomodulation in the inflammatory RMDs. Ann Rheum Dis. 2020;79(8):991–993. doi: 10.1136/annrheumdis-2020-218019

55. Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 2020 Dec 15. doi: 10.1097/ BOR.0000000000000776

56. Novelli L, Motta F, De Santis M, Ansari AA, Gershwin ME, Selmi C. The JANUS of chronic inflammatory and autoimmune diseases onset during COVID-19 – A systematic review of the literature. J Autoimmunity. 2021;117:102592. doi:10.1016/j.jaut2020.102529

57. Ciaffi J, Meliconi R, Ruscitti P, Berardicurti O, Giacomelli R, Ursini F. Rheumatic manifestations of COVID-19: A systematic review and meta-analysis. BMC Rheumatol. 2020;4:65. doi: 10.1186/s41927-020-00165-0

58. Smatti MK, Cyprian FS, Nasrallah GK, Thani AA, Almishal RO, Yassine HM. Viruses and autoimmunity: A review on the potential interaction and molecular mechanisms. Viruses. 2019;11(8):762. doi: 10.3390/v11080762

59. Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol. 2020;217:108480. doi: 10.1016/j.clim.2020.108480

60. Halpert G, Shoenfeld Y. SARS-CoV-2, the autoimmune virus. Autoimmun Rev. 2020;19(12):102695. doi: 10.1016/j.autrev.2020.102695

61. Karaderi T, Bareke H, Kunter I, Seytanoglu A, Cagnan I, et al. Host genetics at the intersection of autoimmunity and COVID-19: A potential key for heterogeneous COVID-19 severity. Front Immunol. 2020;11:586111. doi: 10.3389/fimmu.2020.586111

62. Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: Challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906–918. doi: 10.1182/blood-2018-11-882993

63. Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, et al. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nat Rev Cardiol. 2020;1–16. doi: 10.1038/s41569-020-00469-1

64. McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2020;2(7):e437–e445. doi: 10.1016/S2665-9913(20)30121-1

65. Merrill JT, Erkan D, Winakur J, James JA. Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications. Nat Rev Rheumatol. 2020;16(10):581–589. doi: 10.1038/s41584-020-0474-5

66. Насонов ЕЛ, Решетняк ТМ, Алекберова ЗС. Тромботическая микроангиопатия в ревматологии: связь тромбовоспаления и аутоиммунитета. Терапевтический архив. 2020;92(5). doi: 10.26442/00403660.2020.05.000697

67. Iba T, Levy JH, Connors JM, Warkentin TE, Thachil J, Levi M. The unique characteristics of COVID-19 coagulopathy. Crit Care. 2020;24(1):360. doi: 10.1186/s13054-020-03077-0

68. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020;8(6):e46–e47. doi: 10.1016/S2213-2600(20)30216-2

69. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. doi: 10.1016/ S0140-6736(20)30937-5

70. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta. 2020;507:167–173. doi: 10.1016/j.cca.2020.04.027

71. Trump S, Lukassen S, Anker MS, Chua RL, Liebig J, Thürmann L, et al. Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19. Nat Biotechnol. 2020. doi: 10.1038/S41587-020-00796-1

72. Song W-C, FitzGerald GA. COVID-19, microangiopathy, hemostatic activation, and complement. J Clin Invest. 2020;130(8):3950– 3953. doi: 10.1172/JCI140183

73. Lo MW, Kemper C, Woodruff TM. COVID-19: Complement, coagulation, and collateral damage. J Immunol. 2020;205(6):1488–1495. doi: 10.4049/jimmunol.2000644

74. Trouw LA, Pickering MC, Blom AM. The complement system as a potential therapeutic target in rheumatic disease. Nat Rev Rheumatol. 2017;13(9):538–547. doi: 10.1038/nrrheum.2017.125

75. Baines AC, Brodsky RA. Complementopathies. Blood Rev. 2017;31(4):213–223. doi: 10.1016/j.blre.2017.02.003

76. Holter JC, Pischke SE, de Boer E, Lind A, Jenum S, et al. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proc Natl Acad Sci USA. 2020;117(40):25018–25025. doi: 10.1073/pnas.2010540117

77. Cugno M, Meroni PL, Gualtierotti R, Griffini S, Grovetti E, et al. Complement activation and endothelial perturbation parallel COVID-19 severity and activity. J Autoimmun. 2021;116:102560. doi: 10.1016/j.jaut.2020.102560

78. Антифосфолипидный синдром. Под ред. ЕЛ Насонова, М.: Литтерра;2004:424..

79. Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med. 2018;378(21):2010–2021. doi: 10.1056/NEJMra1705454

80. Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: Understanding the antibodies. Nat Rev Rheumatol. 2011;7(6):330–339. doi: 10.1038/nrrheum.2011.52

81. Cervera R, Rodríguez-Pintó I, Espinosa G. The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: A comprehensive review. J Autoimmun. 2018;92:1–11. doi: 10.1016/j.jaut.2018.05.007

82. Chaturvedi S, Braunstein EM, Yuan X, Yu J, Alexander A, Chen H, et al. Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood. 2020;135(4):239–251. doi: 10.1182/blood.2019003863

83. Gkrouzman E, Barbhaiya M, Erkan D, Lockshin MD. Reality check on antiphospholipid antibodies in COVID-19-associated coagulopathy. Arthritis Rheumatol. 2020 Jul 31. doi: 10.1002/art.41472

84. Mendoza-Pinto C, Garcia-Carrasco M, Cervera R. Role of infectious disease in the antiphospholipid syndrome (including its catastrophic variant). Curr Rheumatol Rep. 2018;20(10):62. doi: 10.1007/s11926-018-0773-x

85. Abdel-Wahab N, Talathi S, Lopez-Olivo MA, Suarez-Almazor ME. Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis. Lupus. 2018;27(4):572–583. doi: 10.1177/0961203317731532

86. Zhang Y, Cao W, Jiang W, Xiao M, Li Y, Tang N, Liu Z, Yan X, Zhao Y, Li T, Zhu T. Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. J Thromb Thrombolysis. 2020;50(3):580–586. doi: 10.1007/s11239-020-02182-9.

87. Xiao M, Zhang Y, Zhang S, Qin X, Xia P, et al. Anti-phospholipid antibodies in critically ill patients with Coronavirus Disease 2019 (COVID-19). Arthritis Rheumatol. 2020;72(12):1998–2004. doi: 10.1002/art.41425

88. Althaus K, Marini I, Zlamal J, Pelzl L, Singh A et al. Antibodyinduced procoagulant platelets in severe COVID-19 infection. Blood. 2020 Dec 23:blood.2020008762. doi: 10.1182/blood.2020008762

89. Shi H, Zuo Y, Gandhi AA, Sule G, Yalavarthi S, et al. Endothelial cell-activating antibodies in COVID-19. medRxiv 2021.01.18.21250041. doi: 10.1101/2021.01.18.21250041

90. Pignatelli P, Ettorre E, Menichelli D, Pani A, Violi F, Pastori D. Seronegative antiphospholipid syndrome: refining the value of «non-criteria» antibodies for diagnosis and clinical management. Haematologica. 2020;105(3):562–572. doi: 10.3324/haematol.2019.221945

91. Litvinova E, Darnige L, Kirilovsky A, Burnel Y, de Luna G, Dragon-Durey MA. Prevalence and significance of non-conventional anti-phospholipid antibodies in patients with clinical APS criteria. Front Immunol. 2018;9:2971. doi: 10.3389/fimmu.2018.02971

92. Hasan Ali O, Bomze D, Risch L, Brugger SD, Paprotny M, et al. Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies. Clin Infect Dis. 2020 Sep 30:ciaa1496. doi: 10.1093/cid/ciaa1496

93. Zuniga M, Gomes C, Carsons SE, Bender MT, Cotzia P, et al. Autoimmunity to the lung protective phospholipid-binding protein annexin A2 predicts mortality among hospitalized COVID-19 patients. medRxiv 2020.12.28.20248807; doi: 10.1101/2020.12.28.20 248807

94. Dallacasagrande V, Hajjar KA. Annexin A2 in inflammation and host defense. Cells. 2020;9(6):1499. doi: 10.3390/cells9061499

95. Cañas F, Simonin L, Couturaud F, Renaudineau Y. Annexin A2 autoantibodies in thrombosis and autoimmune diseases. Thromb Res. 2015;135(2):226–230. doi: 10.1016/j.thromres.2014.11.034

96. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652. doi: 10.1084/jem.20200652

97. Apel F, Zychlinsky A, Kenny EF. The role of neutrophil extracellular traps in rheumatic diseases. Nat Rev Rheumatol. 2018;14(8):467–475. doi: 10.1038/s41584-018-0039-z

98. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):138999. doi: 10.1172/jci.insight.138999

99. Zuo Y, Zuo M, Yalavarthi S, Gockman K, Madison JA, et al. Neutrophil extracellular traps and thrombosis in COVID-19. Neutrophil extracellular traps in COVID-19. medRxiv. 2020.04.30.20086736. doi: 10.1101/2020.04.30.20086736

100. Yalavarthi S, Gould TJ, Rao AN, Mazza LF, et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: A newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 2015;67(11):2990–3003. doi: 10.1002/art.39247

101. Meng H, Yalavarthi S, Kanthi Y, Mazza LF, Elfline MA, et al. In vivo role of neutrophil extracellular traps in antiphospholipid antibody-mediated venous thrombosis. Arthritis Rheumatol. 2017;69(3):655–667. doi: 10.1002/art.39

102. Sule G, Kelley WJ, Gockman K, Yalavarthi S, Vreede AP, et al. Increased adhesive potential of antiphospholipid syndrome neutrophils mediated by β2 integrin Mac-1. Arthritis Rheumatol. 2020;72(1):114–124. doi: 10.1002/art.41057

103. Zuo Y, Estes SK, Ali RA, Gandhi AA, Yalavarthi S,et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. 2020;12(570):eabd3876. doi: 10.1126/scitranslmed.abd3876

104. El Hasbani G, Taher AT, Jawad A, Uthman I. COVID-19, antiphospholipid antibodies, and catastrophic antiphospholipid syndrome: A possible association? Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120978667. doi: 10.1177/1179544120978667

105. Didier K, Bolko L, Giusti D, Toquet S, Robbins A, Antonicelli F, Servettaz A. Autoantibodies associated with connective tissue diseases: What meaning for clinicians? Front Immunol. 2018;9:541. doi: 10.3389/fimmu.2018.00541

106. Zhou Y, Han T, Chen J, Hou C, Hua L, et al. Clinical and autoimmune characteristics of severe and critical cases of COVID-19. Clin Transl Sci. 2020;13(6):1077–1086. doi: 10.1111/cts.12805

107. Shah S, Danda D, Kavadichanda C, Das S, Adarsh MB, Negi VS. Autoimmune and rheumatic musculoskeletal diseases as a consequence of SARS-CoV-2 infection and its treatment. Rheumatol Int. 2020;40(10):1539–1554. doi: 10.1007/s00296-020-04639-9

108. Wang EY, Mao T, Klein J, Dai Y, Huck JD, et al. Diverse functional autoantibodies in patients with COVID-19. medRxiv. 2020 D ec 12:2020.12.10.20247205. doi: 10.1101/2020.12.10.20247205

109. Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, et al. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020;79(12):1661–1663. doi: 10.1136/annrheumdis-2020-218009

110. Lerma LA, Chaudhary A, Bryan A, Morishima C, Wener MH, Fink SL. Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19). J Transl Autoimmun. 2020;3:100073. doi: 10.1016/j.jtauto.2020.100073

111. Gazzaruso C, Stella NC, Mariani G, Nai C, Coppola A, et al. High prevalence of antinuclear antibodies and lupus anticoagulant in patients hospitalized for SARS-CoV2 pneumonia. Clin Rheumatol. 2020 May 27:1–3. doi: 10.1007/s10067-020-05180-7

112. Gagiannis D, Steinestel J, Hackenbroch C, Schreiner B, Hannemann M, et al. Clinical, serological, and histopathological similarities between severe COVID-19 and acute exacerbation of connective tissue disease-associated interstitial lung disease (CTD-ILD). Front Immunol. 2020;11:587517. doi: 10.3389/fimmu.2020.587517

113. Pascolini S, Vannini A, Deleonardi G, Ciordinik M, Sensoli A, Carletti I, et al. COVID-19 and immunological dysregulation: can autoantibodies be useful? Clin Transl Sci. 2020;10.1111/cts.12908. doi: 10.1111/cts.12908

114. Ludwig RJ, Vanhoorelbeke K, Leypoldt F, Kaya Z, Bieber K, et al. Mechanisms of Autoantibody-Induced Pathology. Front Immunol. 2017;8:603. doi: 10.3389/fimmu.2017.00603

115. Gomes C, Zuniga M, Crotty KA, Qian K, Lin LH, et al. Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients. medRxiv 2021.01.04.20249054. doi: 10.1101/2 021.01.04.20249054

116. Cheng AP, Cheng MP, Gu W, Lenz JS, Hsu E, et al. Cell-free DNA in blood reveals significant cell, tissue and organ specific injury and predicts COVID-19 severity. medRxiv 2020.07.27.20163188. doi: 10.1101/2020.07.27.20163188

117. Graney BA, Fischer A. Interstitial pneumonia with autoimmune features. Ann Am Thorac Soc. 2019;16(5):525–533. doi: 10.1513/AnnalsATS.201808-565CME

118. Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020;56(3):2001618. doi: 10.1183/13993003.01618-2020

119. De Lorenzis E, Natalello G, Gigante L, Verardi L, Bosello SL, Gremese E. What can we learn from rapidly progressive interstitial lung disease related to anti-MDA5 dermatomyositis in the management of COVID-19? Autoimmun Rev. 2020;19(11):102666. doi: 10.1016/j.autrev.2020.102666

120. Dias Junior AG, Sampaio NG, Rehwinkel J. A balancing act: MDA5 in antiviral immunity and autoinflammation. Trends Microbiol. 2019;27(1):75–85. doi: 10.1016/j.tim.2018.08.007

121. Sakamoto N, Ishimoto H, Nakashima S. Clinical features of anti-MDA5 antibody-positive rapidly progressive interstitial lung disease without signs of dermatomyositis. Intern Med. 2019;58(6):837–841. doi: 10.2169/internalmedicine.1516-18

122. Gono T, Kaneko H, Kawaguchi Y. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). 2014;53(12):2196–2203. doi: 10.1093/rheumatology/keu258

123. Sato S, Kuwana M, Fujita T. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol. 2013;23(3):496–502. doi: 10.1007/s10165-012-0663-4

124. Fujii H, Tsuji T, Yuba T, Tanaka S, Suga Y, et al. High levels of anti-SSA/Ro antibodies in COVID-19 patients with severe respiratory failure: a case-based review: High levels of anti-SSA/Ro antibodies in COVID-19. Clin Rheumatol. 2020;39(11):3171–3175. doi: 10.1007/s10067-020-05359-y

125. Buvry C, Cassagnes L, Tekath M, Artigues M, Pereira B, et al. Anti-Ro52 antibodies are a risk factor for interstitial lung disease in primary Sjögren syndrome. Respir Med. 2020;163:105895. doi: 10.1016/j.rmed.2020.105895

126. Sabbagh S, Pinal-Fernandez I, Kishi T, Targoff IN, Miller FW, Rider LG, Mammen AL; Childhood Myositis Heterogeneity Collaborative Study Group. Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis. Ann Rheum Dis. 2019;78(7):988–995. doi: 10.1136/annrheumdis-2018-215004

127. Maier C, Wong A, Woodhouse I, Schneider F, Kulpa D, Silvestri G. Broad auto-reactive IgM responses are common in critically ill COVID-19 patients. Res Sq. 2020 Dec 31:rs.3.rs-128348. doi: 10.21203/rs.3.rs-128348/v1

128. Chang SE, Feng A, Meng W, Apostolidis SA, Mack E, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. medRxiv. 2021.01.27.21250559. doi: 10.1101/2021.01.27 .21250559

129. Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Front Immunol. 2021 Jan 19;11:617089. doi: 10.3389/fimmu.2020.617089

130. Lyons-Weiler J. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity. J Transl Autoimmun. 2020;3:100051. doi: 10.1016/j.jtauto.2020.100051

131. Kanduc D, Shoenfeld Y. Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. Immunol Res. 2020;68(5):310–313. doi: 10.1007/s12026-020-09152-6

132. Kharlamova N, Dunn N, Bedri SK, Jerling S, Almgren M, et al. SARS-CoV-2 serological tests can generate false positive results for samples from patients with chronic inflammatory diseases. medRxiv. 2020.11.13.20231076. doi: 10.1101/2020.11.13.20231076

133. Lopez L, Sang PC, Tian Y, Sang Y. Dysregulated interferon response underlying severe COVID-19. Viruses. 2020;12(12):1433. doi: 10.3390/v12121433

134. Насонов ЕЛ, Авдеева АС. Иммуновоспалительные ревматические заболевания, связанные с интерфероном типа I: новые данные. Научно-практическая ревматология. 2019;57(4):452–461. [Nasonov EL, Avdeeva AS. Immunoinflammatory rheumatic diseases associated with type I interferon: New evidence. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2019;57(4):452–461 (In Russ.)]. doi: 10.14412/1995-4484-2019-452-461

135. Fernandez-Ruiz R, Paredes JL, Niewold TB. COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease. Transl Res. 2020:S1931-5244(20)30302-9. doi: 10.1016/j.trsl.2020.12.007

136. Postal M, Vivaldo JF, Fernandez-Ruiz R, Paredes JL, Appenzeller S, Niewold TB. Type I interferon in the pathogenesis of systemic lupus erythematosus. Curr Opin Immunol. 2020;67:87–94. doi: 10.1016/j.coi.2020.10.014

137. Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039. doi: 10.1038/nrdp.2016.39

138. Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036–1045.e9. doi: 10.1016/j.cell.2020.04.026

139. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718–724. doi: 10.1126/science.abc6027

140. Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. doi: 10.1126/science.abd4570

141. Niewold TB. Advances in lupus genetics. Curr Opin Rheumatol. 2015;27(5):440–447. doi: 10.1097/BOR.0000000000000205

142. Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. doi: 10.1126/science.abd4585

143. Howe HS, Leung BPL. Anti-cytokine autoantibodies in systemic lupus erythematosus. Cells. 2019;9(1):72. doi: 10.3390/cells9010072

144. Gupta S, Tatouli IP, Rosen LB, Hasni S, Alevizos I, et al. Distinct functions of autoantibodies against interferon in systemic lupus erythematosus: A comprehensive analysis of anticytokine autoantibodies in common rheumatic diseases. Arthritis Rheumatol. 2016;68(7):1677–1687. doi: 10.1002/art.39607

145. Fernandez-Ruiz R, Masson M, Kim MY, Myers B, Haberman RH, et al.; NYU WARCOV Investigators. Leveraging the United States epicenter to provide insights on COVID-19 in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2020;72(12):1971–1980. doi: 10.1002/art.41450

146. Gupta S, Nakabo S, Chu J, Hasni S, Kaplan MJ. Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus. medRxiv. 2020;2020.10.29.20222000. doi: 10.1101/2020.10.29.20222000

147. Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, et al.; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3):211–221. doi: 10.1056/NEJMoa1912196

148. Woodruff MC, Ramonell RP, Nguyen DC, Cashman KS, Saini AS, et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nat Immunol. 2020;21(12):1506–1516. doi: 10.1038/s41590-020-00814-z

149. Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, et al. Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity. 2018;49(4):725–739.e6. doi: 10.1016/j.immuni.2018.08.015 Erratum in: Immunity. 2020;52(1):203.

150. Jenks SA, Cashman KS, Woodruff MC, Lee FE, Sanz I. Extrafollicular responses in humans and SLE. Immunol Rev. 2019;288(1):136–148. doi: 10.1111/imr.12741

151. Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H, et al.; Massachusetts Consortium on Pathogen Readiness Specimen Working Group. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell. 2020;183(1):143–157.e13. doi: 10.1016/j.cell.2020.08.025

152. Maier-Moore JS, Horton CG, Mathews SA, Confer AW, Lawrence C, et al. Interleukin-6 deficiency corrects nephritis, lymphocyte abnormalities, and secondary Sjögren’s syndrome features in lupus-prone Sle1.Yaa mice. Arthritis Rheumatol. 2014;66(9):2521–2231. doi: 10.1002/art.38716

153. Lu L, Zhang H, Dauphars DJ, He YW. A potential role of interleukin 10 in COVID-19 pathogenesis. Trends Immunol. 2021;42(1):3–5. doi: 10.1016/j.it.2020.10.012

154. Geginat J, Vasco M, Gerosa M, Tas SW, Pagani M, et al. IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus. Semin Immunol. 2019;44:101330. doi: 10.1016/j.smim.2019.101330

155. Godsell J, Rudloff I, Kandane-Rathnayake R, Hoi A, Nold MF, Morand EF, et al. Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus. Sci Rep. 2016;6:34604. doi: 10.1038/srep34604

156. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123–1130. doi: 10.1080/22221751.2020.1770129.

157. Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, et al. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus. Proc Natl Acad Sci USA. 2020;117(13):7305–7316. doi: 10.1073/pnas.1917834117

158. Jog N, DeJager W, Guthridge J, James J. Epstein–Barr virus interleukin 10 in SLE pathogenesis [abstract]. Arthritis Rheumatol. 2019;71(suppl 10). URL: https://acrabstracts.org/abstract/epstein-barr-virus-interleukin-10-in-sle-pathogenesis

159. Geginat J, Larghi P, Paroni M, Nizzoli G, Penatti A, et al. The light and the dark sides of Interleukin-10 in immune-mediated diseases and cancer. Cytokine Growth Factor Rev. 2016;30:87–93. doi: 10.1016/j.cytogfr.2016.02.003

160. Farris AD, Guthridge JM. Overlapping B cell pathways in severe COVID-19 and lupus. Nat Immunol. 2020;21(12):1478–1480. doi: 10.1038/s41590-020-00822-z

161. Riemekasten G, Cabral-Marques O. Antibodies against angiotensin II type 1 receptor (AT1R) and endothelin receptor type A (ETAR) in systemic sclerosis (SSc)-response. Autoimmun Rev. 2016;15(9):935. doi: 10.1016/j.autrev.2016.04.004

162. Becker MO, Kill A, Kutsche M, Guenther J, Rose A, Tabeling C, et al. Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis. Amer J Resp Crit Care Med. 2014;190(7):808–817. doi: 10.1164/rccm.201403-0442OC

163. Avouac J, Riemekasten G, Meune C, Ruiz B, Kahan A, Allanore Y. Autoantibodies against endothelin 1 type A receptor are strong predictors of digital ulcers in systemic sclerosis. J Rheum. 2014;42(10):1801–1807. doi: 10.3899/jrheum.150061

164. Kill A, Tabeling C, Undeutsch R, Kühl AA, Günther J, Radic M, et al. Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis. Arthritis Res Ther. 2014;16(1):R29. doi: 10.1186/ar4457

165. McMillan P, Uhal BD. COVID-19 – A theory of autoimmunity to ACE-2. MOJ Immunol. 2020;7(1):17–19.

166. Casciola-Rosen L, Thiemann DR, Andrade F, Zambrano MIT, Hooper JE, et al. IgM autoantibodies recognizing ACE2 are associated with severe COVID-19. medRxiv. 2020.10.13.20211664. doi: 10.1101/2020.10.13.20211664

167. Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell. 2020;183(4):982–995.e14. doi: 10.1016/j.cell.2020.09.034

168. Jeong JS, Jiang L, Albino E, Marrero J, Rho HS, Hu J, et al. Rapid identification of monospecific monoclonal antibodies using a human proteome microarray. Mol Cell Proteomics. 2012;11(6):O111.016253. doi: 10.1074/mcp.O111.016253

169. Jones CW, Woodford AL, Platts-Mills TF. Characteristics of COVID-19 clinical trials registered with ClinicalTrials.gov: cross-sectional analysis. BMJ Open. 2020;10:e041276. doi: 10.1136/bmjopen-2020-041276

170. Smolen JS. Treat to target in rheumatology: A historical account on occasion of the 10th anniversary. Rheum Dis Clin North Am. 2019;45(4):477–485. doi: 10.1016/j.rdc.2019.07.001

171. Lu L, Zhang H, Zhan M, Jiang J, Yin H, et al. Preventing mortality in COVID-19 patients: Which cytokine to target in a raging storm? Front Cell Dev Biol. 2020;8:677. doi: 10.3389/fcell.2020.00677

172. Perricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, et al. The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19. J Autoimmun. 2020;111:102468. doi: 10.1016/j.jaut.2020.102468

173. Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF. How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy. Nat Med. 2013;19(7):822–824. doi: 10.1038/nm.3260

174. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155–166. doi: 10.1038/s41584-020-0372-x

175. Dos Reis Neto ER, Kakehasi AM, de Medeiros Pinheiro M, Ferreira GA, Marques CDL, da Mota LMH, et al. Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases. Adv Rheumatol. 2020;60:32. doi: 10.1186/s42358-020-00134-8

176. Berthelot JM, Lioté F, Maugars Y, Sibilia J. Lymphocyte changes in severe COVID-19: Delayed over-activation of STING? Front Immunol. 2020;11:607069. doi: 10.3389/fimmu.2020.607069

177. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932. doi: 10.1016/j.ijantimicag.2020.105932

178. Ghazy RM, Almaghraby A, Shaaban R, Kamal A, Beshir H, et al. A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment. Sci Rep. 2020;10(1):22139. doi: 10.1038/s41598-020-77748-x

179. Mazhar F, Hadi MA, Kow CS, Marran AMN, Merchant HA, Hasan SS. Use of hydroxychloroquine and chloroquine in COVID-19: How good is the quality of randomized controlled trials? Int J Infect Dis. 2020;101:107–120. doi: 10.1016/j.ijid.2020.09.1470

180. Ladapo JA, McKinnon JE, McCullough PA, Risch H. Randomized controlled trials of early ambulatory hydroxychloroquine in the prevention of COVID-19 infection, hospitalization, and death: meta-analysis. medRxiv. 2020. doi: 10.1101/2020.09.30. 20204693

181. Espinola RG, Pierangeli SS, Gharavi AE, Harris EN, Ghara AE. Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost. 2002;87:518–522.

182. Rand JH, Wu X-X, Quinn AS, Ashton AW, Chen PP, Hathcock JJ, et al. Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: Evidence for a novel effect for an old antimalarial drug. Blood. 2010;115:2292–2299. doi: 10.1182/blood-2009-04-213520

183. Urbanski G, Caillon A, Poli C, Kauffenstein G, Begorre M-A, et al. Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome. PLoS One. 2018;13(11):e0206814. doi: 10.1371/journal.pone.0206814

184. Miranda S, Billoir P, Damian L, Thiebaut PA, Schapman D, et al. Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction. PLoS One. 2019;14(3):e0212614. doi: 10.1371/journal.pone.0212614

185. Schmidt-Tanguy A, Voswinkel J, Henrion D, Subra JF, Loufrani L, Rohmer V, et al. Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients. J Thromb Haemost. 2013;11:1927–1929. doi: 10.1111/jth.12363

186. Schreiber K, Breen K, Parmar K, Rand JH, Wu X-X, Hunt BJ. The effect of hydroxychloroquine on haemostasis, complement, inflammation and angiogenesis in patients with antiphospholipid antibodies. Rheumatology (Oxford). 2018;57(1):120–124. doi: 10.1093/rheumatology/kex378

187. Nuri E, Taraborelli M, Andreoli L, Tonello M, Gerosa M, et al. Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syn-drome. Immunol Res. 2017;65(1):17–24. doi: 10.1007/s12026-016-8812-z

188. Kravvariti E, Koutsogianni A, Samoli E, Sfikakis PP, Tektonidou MG. The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study. Autoimmun Rev. 2020;19(4):102491. doi: 10.1016/j. autrev.2020.102491

189. Erkan D, Unlu O, Sciascia S, Belmont HM, Branch DW, et al.; APS ACTION. Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease. Lupus. 2018;27(3):399–406. doi: 10.1177/0961203317724219

190. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69(1):20–8. doi: 10.1136/ard.2008.101766

191. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: A systematic review. Ann Rheum Dis. 2019;78(6):736–745. doi: 10.1136/annrheumdis-2019-215089

192. Infante M, Ricordi C, Fabbri A. Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: Risks and benefits at the time of COVID-19 pandemic. J Diabetes. 2020;12(9):659– 667. doi: 10.1111/1753-0407.13053

193. Chen C, Pan K, Wu B, Li X, Chen Z, Xu Q, et al.. Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials. Eur J Clin Pharmacol. 2021;77(1):13–24. doi: 10.1007/s00228-020-02962-5

194. World Health Organization. Clinical management of COVID-19. URL: https://www.who.int/publications/i/item/clinical-management-of-covid-19 (Accessed 14th October 2020).

195. Meduri GU, Annane D, Confalonieri M, Chrousos GP, et al. Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med. 2020;46(12):2284–2296. doi: 10.1007/s00134-020-06289-8

196. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus [nCoV] infection is suspected. URL: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novelcoronavirus-[ncov]-infection-is-suspected (Accessed 9th February 2020).

197. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473–475. doi: 10.1016/S0140-6736(20)30317-2

198. Buttgereit F. Views on glucocorticoid therapy in rheumatology: the age of convergence. Nat Rev Rheumatol. 2020;16(4):239–246. doi: 10.1038/s41584-020-0370-z

199. Hardy RS, Raza K, Cooper MS. Therapeutic glucocorticoids: mechanisms of actions in rheumatic disease. Nat Rev Rheumatol. 2020;16(3):133–144. doi: 10.1038/s41584-020-0371-y

200. Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233–247. doi: 10.1038/nri.2017.1

201. Franco LM, Gadkari M, Howe KN, Sun J, Kardava L, et al. Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses. J Exp Med. 2019;216(2):384– 406. doi: 10.1084/jem.20180595

202. Park JH, Lee HK. Re-analysis of single cell transcriptome reveals that the NR3C1-CXCL8-neutrophil axis determines the severity of COVID-19. Front Immunol. 2020;11:2145. doi: 10.3389/ fimmu.2020.02145

203. Ferrara F, Vitiello A. Efficacy of synthetic glucocorticoids in COVID-19 endothelites. Naunyn Schmiedebergs Arch Pharmacol. 2021 Jan 14:1–5. doi: 10.1007/s00210-021-02049-7

204. Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS. Long-term side effects of glucocorticoids. Expert Opin Drug Saf. 2016;15(4):457–465. doi: 10.1517/14740338.2016.1140743

205. RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19 – Preliminary report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. doi: 10.1056/NEJMoa2021436

206. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA. 2020;324(13):1330– 1341. doi: 10.1001/jama.2020.17023

207. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, et al.. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA. 2020;324(13):1317–1329. doi: 10.1001/jama.2020.17022

208. Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, et al.; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A ran- domized clinical trial. JAMA. 2020;324(13):1298–1306. doi: 10.1001/jama.2020.16761

209. Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with COVID-19 (Metcovid): A randomised, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis. 2020 Aug 12:ciaa1177. doi: 10.1093/cid/ciaa1177

210. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, et al; COALITION COVID-19 Brazil III Investigators. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX randomized clinical trial. JAMA. 2020;324(13):1307–1316. doi: 10.1001/jama.2020.17021

211. Van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Crit Care. 2020;24(1):696. doi: 10.1186/s13054-020-03400-9

212. Shuto H, Komiya K, Yamasue M, Uchida S, Ogura T, et al. A systematic review of corticosteroid treatment for noncritically ill patients with COVID-19. Sci Rep. 2020;10(1):20935. doi: 10.1038/s41598-020-78054-2

213. Cano EJ, Fuentes XF, Campioli CC, O’Horo JC, Saleh OA, Odeyemi Y et al. Impact of corticosteroids in coronavirus disease 2019 outcomes: Systematic review and meta-analysis. Chest. 2020:S0012-3692(20)35107-2. doi: 10.1016/j.chest.2020.10.054

214. WHO updates guidance on corticosteroids in Covid-19 patients. (Acessed: 3rd September 2020).

215. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, et al. American College of Rheumatology Clinical Guidance for pediatric patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in COVID-19. Version 2. Arthritis Rheumatol. 2020 Dec 5. doi: 10.1002/art.41616

216. Matthay MA, Wick KD. Corticosteroids, COVID-19 pneumonia, and acute respiratory distress syndrome. J Clin Invest. 2020;130(12):6218–6221. doi: 10.1172/JCI143331

217. Liu J, Zhang S, Dong X, Li Z, Xu Q, et al. Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome. J Clin Invest. 2020;130(12):6417–6428. doi: 10.1172/JCI140617

218. Bartoletti M, Marconi L, Scudeller L, Pancaldi L, Tedeschi S, et al.; PREDICO Study Group. Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: A multicentre study. Clin Microbiol Infect. 2021;27(1):105–111. doi: 10.1016/j.cmi.2020.09.014

219. Liu Z, Li X, Fan G, Zhou F, Wang Y, et al. Low-to-moderate dose corticosteroids treatment in hospitalized adults with COVID-19. Clin Microbiol Infect. 2021;27(1):112–117. doi: 10.1016/j.cmi.2020.09.045

220. Li Y, Meng Q, Rao X, Wang B, Zhang X, et al. Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study. Crit Care. 2020;24(1):698. doi: 10.1186/s13054-020-03429-w

221. Wu C, Hou D, Du C, Cai Y, Zheng J, et al. Corticosteroid therapy for coronavirus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis. Crit Care. 2020;24(1):643. doi: 10.1186/s13054-020-03340-4

222. Albani F, Fusina F, Granato E, Capotosto C, Ceracchi C, et al. Corticosteroid treatment has no effect on hospital mortality in COVID-19 patients. Sci Rep. 2021;11(1):1015. doi: 10.1038/s41598-020-80654-x

223. Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013;48(6):742–748. doi: 10.1165/rcmb.2012-0339OC

224. Keller MJ, Kitsis EA, Arora S, Chen JT, Agarwal S, Ross MJ, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. J Hosp Med. 2020;15(8):489–493. doi: 10.12788/jhm.3497

225. Coelho MC, Santos CV, Vieira Neto L, Gadelha MR. Adverse effects of glucocorticoids: coagulopathy. Eur J Endocrinol. 2015;173(4):M11-21. doi: 10.1530/EJE-15-0198

226. Johannesdottir SA, Horváth-Puhó E, Dekkers OM, Cannegieter SC, Jørgensen JO, Ehrenstein V, et al. Use of glucocorticoids and risk of venous thromboembolism: A nationwide population-based case-control study. JAMA Intern Med. 2013;173(9):743–752. doi: 10.1001/jamainternmed.2013.122

227. van Zaane B, Nur E, Squizzato A, Gerdes VE, Büller HR, et al. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemost. 2010;8(11):2483–2493. doi: 10.1111/j.1538-7836.2010.04034.x

228. Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP. Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma. Respir Res. 2017;18(1):207. doi: 10.1186/s12931-017-0689-4

229. Alessi J, de Oliveira GB, Schaan BD, Telo GH. Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes. Diabetol Metab. 2020;Syndr 12:80. doi: 10.1186/s13098-020-00583-7

230. Villar J, Confalonieri M, Pastores SM, Meduri GU. Rationale for prolonged corticosteroid treatment in the acute respiratory distress syndrome caused by coronavirus disease 2019. Crit Care Explor. 2020;2(4):e0111. doi: 10.1097/CCE.0000000000000111

231. Lamontagne SJ, Pizzagalli DA, Olmstead MC. Does inflammation link stress to poor COVID-19 outcome? Stress Health. 2020 Dec 14. doi: 10.1002/smi.3017

232. Isidori AM, Arnaldi G, Boscaro M, Falorni A, Giordano C, et al. COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency. J Endocrinol Invest. 2020;43(8):1141– 1147. doi: 10.1007/s40618-020-01266-w

233. Akiyama S, Hamdeh S, Micic D, Sakuraba A. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: A systematic review and meta-analysis. Ann Rheum Dis. 2020 Oct 13:annrheumdis-2020-218946. doi: 10.1136/annrheumdis-2020-218946

234. Favalli EG, Bugatti S, Klersy C, Biggioggero M, Rossi S, et al. Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis. Arthritis Res Ther. 2020;22(1):290. doi: 10.1186/s13075-020-02395-6

235. Yao T-C, Huang Y-W, Chang S-M, Tsai S-Y, Chen Wu A, Tsai H-J. Association between oral corticosteroid bursts and severe adverse events: A nationwide population-based cohort study. Ann Intern Med. 2020;173(5):325–330. doi: 10.7326/M20-0432

236. Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol. 2020;146(3):518–534.e1. doi: 10.1016/j.jaci.2020.07.001

237. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959–970. doi: 10.2217/imt-2016-0

238. Lan SH, Lai CC, Huang HT, Chang SP, Lu LC, Hsueh PR. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents. 2020;56(3):106103. doi: 10.1016/j.ijantimicag.2020.106103

239. Boregowda U, Perisetti A, Nanjappa A, Gajendran M, Kutti Sridharan G, Goyal H. Addition of tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis. Front Med (Lausanne). 2020;7:586221. doi: 10.3389/fmed.2020.586221

240. Han Q, Guo M, Zheng Y, Zhang Y, De Y, et al. Current evidence of interleukin-6 signaling inhibitors in patients with COVID-19: A systematic review and meta-analysis. Front Pharmacol. 2020;11:615972. doi: 10.3389/fphar.2020.615972

241. Khan F, Stewart I, Fabbri L, Moss S, Robinson KA, et al. A systematic review of Anakinra, Sarilumab, Siltuximab with meta-analysis of Tocilizumab for Covid-19. medRxiv. 2020.04.23.20076612. doi: 10.1101/2020.04.23.20076612

242. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, et al. Effect of tocilizumab vs standard of care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med. 2020. doi: 10.1001/jamainternmed.2020.6615

243. Hermine O, Mariette X, Tharaux P-L, Resche-Rigon M, Porcher R, Ravaud P; for the CORIMUNO-19 Collaborative Group. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2020. doi: 10.1001/jamainternmed.2020.6820

244. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, et al. MK; BACC Bay Tocilizumab Trial Investigators. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333–2344. doi: 10.1056/NEJMoa2028836

245. Rosas I, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with COVID-19 pneumonia. URL: https://www.medrxiv.org/content/10.1101/2020.08.27.20183442v2 (Accessed 12th September 2020).

246. Salama C, Han J, Yau L, Reiss WG, Kramer B, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30. doi: 10.1056/NEJMoa2030340

247. The REMAP-CAP Investigators, Gordon CA, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19 – Preliminary report. medRxiv. 2021.01.07.21249390; doi: 10.1101/2021.01.07.212 49390

248. Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, et al.; Coalition COVID-19 Brazil VI Investigators. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: Randomised controlled trial. BMJ. 2021 Jan 20;372:n84. doi: 10.1136/bmj.n84

249. RECOVERY Collaborative Group, Horby PW, Pessoa-Amorim G, eto L, Brightling CE, Sarkar R, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. medRxiv 2021.02.11.21249258; doi: https://doi.org/10.1101/2021.02.11.21249258

250. Regeneron and Sanofi Begin Global Kevzara (Sarilumab) Clinical Trial Program in patients with severe COVID-19. 2020 Mar 16. URL: https://investor.regeneron.com/news-releases/news-re-lease-details/regeneron-and-sanofi-begin-global-kevzarar-sarilumab-clinical.

251. Maude S, Barrett DM. Current status of chimeric antigen receptor therapy for haematological malignancies. Br J Haematol. 2016;172(1):11–22. doi: 10.1111/bjh.13792

252. Diaz-Torne C, Ortiz MDA, Moya P, Hernandez MV, Reina D, Castellvi I, et al. The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab. Semin Arthritis Rheum. 2018;47(6):757–764. doi: 10.1016/j.semarthrit.2017.10.022

253. Berti A, Cavalli G, Campochiaro C, et al. Interleukin-6 in ANCA-associated vasculitis: Rationale for successful treatment with tocilizumab. Semin Arthritis Rheum. 2015;45(1):48–54. doi: 10.1016/j.semarthrit.2015.02.002

254. Umare V, Nadkarni A, Nadkar M, et al. Do high sensitivity C-reactive protein and serum interleukin-6 levels correlate with disease activity in systemic lupus erythematosus patients? J Postgrad Med. 2017;63(2):92–95.

255. van Gameren MM, Willemse PH, Mulder NH, et al. Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. Blood. 1994;84(5):1434–1441.

256. Velazquez-Salinas L, Verdugo-Rodriguez A, Rodriguez LL, Borca MV. The role of interleukin 6 during viral infections. Front Microbiol. 201910:1057. doi: 10.3389/fmicb.2019.01057

257. Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol. 2017;13:399–409. doi: 10.1038/nrrheum.2017.83

258. Rubio-Rivas M, Mora-Lujan JM, Montero A, Homs NA, Rello J, et al. Beneficial and harmful outcomes of tocilizumab in severe COVID-19: A systematic review and meta-analysis. medRxiv. 2020.09.05.20188912. doi: 10.1101/2020.09.05.20188912

259. Mazzoni A, Salvati L, Maggi L, Capone M, Vanni A, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest. 2020 Sep 1;130(9):4694–4703. doi: 10.1172/JCI138554

260. Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020;92(10):1875–1883. doi: 10.1002/jmv.26050

261. Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9. doi: 10.1002/rmv.2141

262. Georgakis MK, Malik R, Gill D, Franceschini N, Sudlow CLM, Dichgans M; INVENT Consortium, CHARGE Inflammation Working Group. Interleukin-6 signaling effects on ischemic stroke and other cardiovascular outcomes: A mendelian randomization study. Circ Genom Precis Med. 2020;13(3):e002872. doi: 10.1161/CIRCGEN.119.002872

263. Bovijn J, Lindgren CM, Holmes MV. Genetic variants mimicking therapeutic inhibition of IL-6 receptor signaling and risk of COVID-19. Lancet Rheumatol. 2020;2(11):e658–e659. doi: 10.1016/S2665-9913(20)30345-3

264. Larsson SC, Burgess S, Gill D. Genetically proxied interleukin-6 receptor inhibition: opposing associations with COVID-19 and pneumonia. Eur Respir J. 2020:2003545. doi: 10.1183/13993003.03545-2020

265. Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, et al. The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) study. Rationale and design. Ann Am Thorac Soc. 2020;17(7):879–891. doi: 10.1513/AnnalsATS.202003-192SD

266. Rubio-Rivas M, Ronda M, Padulles A, Mitjavila F, Riera-Mestre A, et al. Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness. Int J Infect Dis. 2020;101:290–297. doi: 10.1016/j.ijid.2020.09.1486

267. Ruiz-Antorán B, Sancho-López A, Torres F, Moreno-Torres V, et al.; TOCICOV-study group. Combination of tocilizumab and steroids to improve mortality in patients with severe COVID-19 infection: A Spanish, multicenter, cohort study. Infect Dis Ther. 2020 Dec 6:1–16. doi: 10.1007/s40121-020-00373-8

268. Narain S, Stefanov DG, Chau AS, Weber AG, Marder G, et al.; Northwell COVID-19 Research Consortium. Comparative survival analysis of immunomodulatory therapy for coronavirus disease 2019 cytokine storm. Chest. 2020:S0012-3692(20)34901-1. doi: 10.1016/j.chest.2020.09.275

269. Ramiro S, Mostard RLM, Magro-Checa C, van Dongen CMP, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis. 2020;79(9):1143–1151. doi: 10.1136/annrheumdis-2020-218479

270. Mikulska M, Nicolini LA, Signori A, Di Biagio A, Sepulcri C, et al. Tocilizumab and steroid treatment in patients with COVID-19 pneumonia. PLoS One. 2020;15(8):e0237831. doi: 10.1371/journal.pone.0237831

271. Martínez-Urbistondo D, Segovia RC, del Villar Carrero RS, Risco CR, Fernández PV. Early combination of tocilizumab and corticosteroids: An upgrade in anti-inflammatory Therapy for severe coronavirus disease (COVID). Clinical Infectious Disease. 2020;ciaa910, URL: 10.1093/cid/ciaa910

272. Hazbun ME, Faust AC, Ortegon AL, Sheperd LA, Weinstein GL, et al. The combination of tocilizumab and methylprednisolone along with initial lung recruitment strategy in coronavirus disease 2019 patients requiring mechanical ventilation: A series of 21 consecutive cases. Crit Care Explor. 2020;2(6):e0145. doi: 10.1097/CCE.0000000000000145

273. Jiménez-Brítez G, Ruiz P, Soler X. Tocilizumab plus glucocorticoids in severe and critically COVID-19 patients. A single center experience. Med Clin (Barc). 2020;155(9):410–411. doi: 10.1016/j.medcli.2020.07.001

274. Lopez-Medrano F, Asin MAP-J, Fernandez-Ruiz M, Carretero O, et al. Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: a single-center retrospective study. medRxiv. 2020.09.26.20202283; doi: 10.1101/2020.09.26.20202283

275. Kim MS, An MH, Kim WJ, Hwang T-H. Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis. PLoS Med. 2020;17(12):e1003501. doi: 10.1371/journal.pmed.1003501

276. Gupta S, Wang W, Hayek SS, et al. STOP-COVID Investigators Association between early treatment with tocilizumab and mortality among critically ill patients with COVID-19. JAMA Intern Med. 2021;181:41–51. doi: 10.1001/jamainternmed.2020.625

277. Petrak RM, Van Hise NW, Skorodin NC, et al. Early tocilizumab dosing is associated with improved survival in critically ill patients infected with SARS-COV-2. medRxiv. 2020.10.27.20211433. doi: 1 0.1101/2020.10.27.20211433

278. Capra R, De Rossi N, Mattioli F, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020;76:31–5. doi: 10.1016/j.ejim.2020.05.009

279. Langer-Gould A, Smith JB, Gonzales EG, et al. Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab. Int J Infect Dis. 2020;99:291–7. doi: 10.1016/j.ijid.2020.07.081

280. Насонов ЕЛ. Роль интерлейкина 1 в развитии заболеваний человека. Научно-практическая ревматология. 2018;56(Прил. 1):19–27. doi: 10.14412/1995-4484-2018-19-27.

281. Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol. 2019;15(10):612–32. doi: 10.1038/s41584-019-0277-8

282. van de Veerdonk FL, Netea MG. Blocking IL-1 to prevent respiratory failure in COVID-19. Crit Care. 2020;24(1):445. doi: 10.1186/s13054-020-03166-0

283. Kooistra EJ, Waalders NJB, Grondman I, Janssen NAF, de Nooijer AH; the RCI-COVID-19 Study Group. Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study. Crit Care. 2020;24:688. doi: 10.1186/s13054-020-03364-w

284. Aouba A, Baldolli A, Geffray L, et al. Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Ann Rheum Dis. 2020;79(10):1381–1382. doi: 10.1136/annrheumdis-2020-217706

285. Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325– e331. doi: 10.1016/S2665-9913(20)30127-2

286. Navarro-Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH, Crow MK. Use of anakinra to prevent mechanical ventilation in severe COVID-19: A case series. Arthritis Rheumatol. 2020;72(12):1990–1997. doi: 10.1002/art.41422

287. Iglesias-Julián E, López-Veloso M, de-la-Torre-Ferrera N, Barraza-Vengoechea JC, et al. High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients. J Autoimmun. 2020;115:102537. doi: 10.1016/j.jaut.2020.102537

288. Aomar-Millán IF, Salvatierra J, Torres-Parejo Ú, Faro-Miguez N, Callejas-Rubio JL, et al. Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study. Intern Emerg Med. 2021 Jan 5:1–10. doi: 10.1007/s11739-020-02600-z

289. Bozzi G, Mangioni D, Minoia F, Aliberti S, Grasselli G, et al. Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study. J Allergy Clin Immunol. 2020:S0091-6749(20)31621-3. doi: 10.1016/j.jaci.2020.11.006

290. Huet T, Beaussier H, Voisin H, Jouveshomme S, Dauriat G, Lazareth I, et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020;2(7):e393–e400. doi: 10.1016/S2665-9913(20)30164-8

291. Pontali E, Volpi S, Antonucci G, et al. Safety and efficacy of early high-dose IV anakinra in severe COVID-19 lung disease. J Allergy Clin Immunol. 2020;146(1):213–215. doi: 10.1016/j.jaci.2020.05.002

292. Cauchois R, Koubi M, Delarbre D, et al. Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19. Proc Natl Acad Sci USA. 2020;117(32):18951–18953. doi: 10.1073/pnas.2009017117

293. Kyriazopoulou E, Panagopoulos P, Metallidis S, Dalekos GN, Poulakou G, et al. Anakinra to prevent respiratory failure in COVID-19. medRxiv. 2020.10.28.20217455. doi: 10.1101/2020.10.2 8.20217455

294. Balkhair A, Al-Zakwani I, Al Busaidi M, Al-Khirbash A, Al Mubaihsi S, et al. Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study. Int J Infect Dis. 2020;103:288–296. doi: 10.1016/j.ijid.2020.11.149

295. Kooistra EJ, Waalders NJB, Grondman I. et al. Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study. Crit Care. 2020;24:688. doi: 10.1186/s13054-020-03364-w

296. Cavalli G, Lacher A, Tomelleri A, Campochiaro C, Della-Torre E, et al. Interleukin-1 and interleukin-6 inhibition compared with standart management in patients with COVID-19 and hyperinflammation: a cohort studt. Lancet Rheumatol 2021. https://doi.org/10.1016/S2665-993(21)00012-6.

297. Generali D, Bosio G, Malberti F, Cuzzoli A, Testa S, et al. Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study. Int J Infect Dis. 2020:S1201-9712(20)32597-2. doi: 10.1016/j.ijid.2020.12.073

298. Landi L, Ravaglia C, Russo E, Cataleta P, Fusari M, et al. Blockage of interleukin-1β with canakinumab in patients with Covid-19. Sci Rep. 2020;10(1):21775. doi: 10.1038/s41598-020-78492-y

299. Ucciferri C, Auricchio A, Di Nicola M, Potere N, Abbate A, Cipollone F, et al. Canakinumab in a subgroup of patients with COVID-19. Lancet Rheumatol. 2020;2(8):e457–ee458. doi: 10.1016/S2665-9913(20)30167-3

300. Sheng CC, Sahoo D, Dugar S, Prada RA, Wang TKM, et al. Canakinumab to reduce deterioration of cardiac and respiratory function in SARS-CoV-2 associated myocardial injury with heightened inflammation (canakinumab in Covid-19 cardiac injury: The three C study). Clin Cardiol. 2020;43(10):1055–1063. doi: 10.1002/clc.23451

301. CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): A randomised controlled trial. Lancet Respir Med. 2021:S2213-2600(20)30556-7. doi: 10.1016/S2213-2600(20)30556-7

302. Clinicaltrials.gov. Study of efficacy and safety of canakinumab treatment for CRS in participants with COVID-19-induced pneumonia (CAN-COVID). NCT04362813. URL: https://clinicaltrials.gov/ct2/show/NCT04362813 (Accessed November 2020).

303. Winthrop KL, Mariette X, Silva JT, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors). Clin Microbiol Infect. 2018;24 Suppl 2:S21–S40. doi: 10.1016/j.cmi.2018.02.002

304. Cavalli G, Dinarello CA. Anakinra therapy for non-cancer inflammatory diseases. Front Pharmacol. 2018;9:1157. doi: 10.3389/fphar.2018.01157

305. Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med. 2016;44:275–81. doi: 10.1097/CCM.0000000000001402

306. Eloseily EM, Weiser P, Crayne CB, et al. Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis. Arthritis Rheum. 2020;72(2):326–334. doi: 10.1002/art.41103

307. Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol. 2020;2(6):e358–e367. doi: 10.1016/S2665-9913(20)30096-5

308. Monteagudo LA, Boothby A, Gertner E. Continuous intravenous anakinra infusion to calm the cytokine storm in macrophage activation syndrome. ACR Open Rheumatol. 2020;2(5):276–282. doi: 10.1002/acr2.11135

309. Papa R, Natoli V, Caorsi R, et al. Successful treatment of refractory hyperferritinemic syndromes with canakinumab: A report of two cases. Pediatr Rheumatol. 2020;18:56. doi: 10.1186/s12969-020-00450-9

310. Алекберова ЗС, Насонов ЕЛ. Перспективы применения колхицина в медицине: новые данные. Научно-практическая ревматология. 2020;58(2):183–190. doi: 10.14412/1995-4484-2020-183-190

311. Reyes AZ, Hu KA, Teperman J, Wampler Muskardin TL, Tardif JC, Shah B, et al. Anti-inflammatory therapy for COVID-19 infection: the case for colchicine. Ann Rheum Dis. 2020 Dec 8: annrheumdis-2020-219174. doi: 10.1136/annrheumdis-2020-219174

312. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3:e2013136. doi: 10.1001/jamanetworkopen

313. Scarsi M, Piantoni S, Colombo E, et al. Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome. Ann Rheum Dis. 2020;79:1286–1289. doi: 10.1136/annrheumdis-2020-217712

314. Lopes MIF, Bonjorno LP, Giannini MC, et al. Beneficial effects of colchicine for moderate to severe COVID-19: An interim analysis of a randomized, double-blinded, placebo controlled clinical trial. medRxiv. 2020. doi: 10.1101/2020.08.06.20169573

315. Tardif J-C, Bouabdallaoui N, L’Allier PL, Gaudet D, Shah B, et al. Efficacy of colchicine in non-hospitalized patients with COVID-19. medRxiv. 2021.01.26.21250494. doi: 10.1101/2021.01.2 6.21250494

316. Stewart S, Yang KCK, Atkins K, et al. Adverse events during oral colchicine use: A systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther. 2020;22(1):28. doi: 10.1186/s13075-020-2120-7

317. Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843–862. doi: 10.1038/nrd.2017.201

318. Насонов ЕЛ, Лила АМ. Ингибиторы Янус-киназ при иммуновоспалительных ревматических заболеваниях: новые возможности и перспективы. Научно-практическая ревматология. 2019;57(1):8–16. doi: 10.14412/1995-4484-2019-8-16

319. Jorgensen SCJ, Tse CLY, Burry L, Dresser LD. Baricitinib: A review of pharmacology, safety, and emerging clinical experience in COVID-19. Pharmacotherapy. 2020;40(8):843–856. doi: 10.1002/phar.2438

320. Stebbing J, Krishnan V, de Bono S, Ottaviani S, Casalini G, et al.; Sacco Baricitinib Study Group. Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients. EMBO Mol Med. 2020;12(8):e12697. doi: 10.15252/emmm.202012697

321. Bronte V, Ugel S, Tinazzi E, Vella A, De Sanctis F, et al. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J Clin Invest. 2020;130(12):6409–6416. doi: 10.1172/JCI141772

322. Hoang TN, Pino M, Boddapati AK, et al. Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. URL: https://www.biorxiv.org/content/10.1101/2020.09.16.300277v1 (Accessed 16th September 2020)

323. Cantini F, Niccoli L, Nannini C, Matarrese D, Natale MED, et al. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. J Infect. 202;81(4):647–679. doi: 10.1016/j.jinf.2020.06.052

324. Rosas J, Liaño FP, Cantó ML, Barea JMC, Beser AR, et al.; COVID19-HMB Group. Experience with the use of baricitinib and tocilizumab monotherapy or combined, in patients with interstitial pneumonia secondary to coronavirus COVID19: A real-world study. Reumatol Clin. 2020:S1699-258X(20)30271-0. doi: 10.1016/j.reuma.2020.10.009

325. Titanji BK, Farley MM, Mehta A, Connor-Schuler R, Moanna A, et al. Use of baricitinib in patients with moderate and severe COVID-19. Clin Infect Dis. 2020:ciaa879. doi: 10.1093/cid/ciaa879

326. Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2020 Dec 11:NEJMoa2031994. doi: 10.1056/NEJMoa2031994

327. Rodriguez-Garcia JL, Sanchez-Nievas G, Arevalo-Serrano J, Garcia-Gomez C, Jimenez-Vizuete JM, Martinez-Alfaro E. Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study. Rheumatology (Oxford). 2020 Oct 6.

328. Walz L, Cohen AJ, Rebaza AP, Vanchieri J, Slade MD, et al. JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: A systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):47. doi: 10.1186/s12879-020-05730-z

329. Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020;146(1):137-146.e3. doi: 10.1016/j.jaci.2020.05.019

330. Cingolani A, Tummolo AM, Montemurro G, Gremese E, Larosa L, et al. for COVID 2 Columbus Working Group. Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab. Infection. 2020;48(5):767–771. doi: 10.1007/s15010-020-01476-7

331. La Rosée F, Bremer HC, Gehrke I, et al. The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020;34(7):1805–1815. doi: 10.1038/s41375-020-0891-0

332. Wang J, Wang Y, Wu L, Wang X, Jin Z, Gao Z. Ruxolitinib for refractory/relapsed hemophagocytic lymphohistiocytosis. Haematologica. 2019;105:e210–e212.

333. Ahmed A, Merrill SA, Alsawah F, Bockenstedt P, Campagnaro E, et al. Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: An open-label, single-centre, pilot trial. Lancet Haematol. 2019;6(12):e630–e637. doi: 10.1016/S2352-3026(19)30156-5

334. Goldsmith SR, Saif Ur Rehman S, Shirai CL, Vij K, et al. Resolution of secondary hemophagocytic lymphohistiocytosis after treatment with the JAK1/2 inhibitor ruxolitinib. Blood Adv. 2019;3(23):4131–4135. doi: 10.1182/bloodadvances.2019000898

335. Насонов ЕЛ, Лила АМ. Барицитиниб: новые возможности фармакотерапии ревматоидного артрита и других иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2020;58(3):304–316. doi: 10.14412/1995-4484-2020-304-316

336. Mehta P, Ciurtin C, Scully M, Levi M, Chambers RC. JAK inhibitors in COVID-19: The need for vigilance regarding increased inherent thrombotic risk. Eur Respir J. 2020;56(3):2001919. doi: 10.1183/13993003.01919-2020

337. Wong EKS, Kavanagh D. Diseases of complement dysregulation – An overview. Semin Immunopathol. 2018;40(1):49–64. doi: 10.1007/s00281-017-0663-8

338. Diurno F, Numis FG, Porta G, et al. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040–4047. doi: 10.26355/eurrev_202004_20875

339. Laurence J, Mulvey JJ, Seshadri M, Racanelli A, Harp J, Schenck EJ, et al. Anti-complement C5 therapy with eculizumab in three cases of critical COVID-19. Clin Immunol. 2020;219:108555. doi: 10.1016/j.clim.2020.108555

340. Raghunandan S, Josephson CD, Verkerke H, et al. Complement inhibition in severe COVID-19 acute respiratory distress syndrome. Front Pediatr. 2020;8:616731. doi: 10.3389/fped.2020.616731

341. Peffault de Latour R, Bergeron A, Lengline E, Dupont T, Marchal A, Galicier L, et al. Complement C5 inhibition in patients with COVID-19 – a promising target? Haematologica. 2020;105(12):2847–2850. doi: 10.3324/haematol.2020.260117

342. Mastaglio S, Ruggeri A, Risitano AM, Angelillo P, Yancopoulou D, Mastellos DC, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450. doi: 10.1016/j.clim.2020.108450

343. Mastaglio S, Ruggeri A, Risitano AM, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020:108450. doi: 10.1016/j.clim.2020.108450

344. Patriquin CJ, Kuo KHM. Eculizumab and beyond: The past, present, and future of complement therapeutics. Transfus Med Rev. 2019;33(4):256–265. doi: 10.1016/j.tmrv.2019.09.004

345. Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1):e20190945. doi: 10.1084/jem.20190945

346. Mehta P, Porter JC, Manson JJ, Isaacs JD, Openshaw PJM, et al. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: Challenges and opportunities. Lancet Respir Med. 2020;8(8):822–830. doi: 10.1016/S2213-2600(20)30267-8

347. Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020;20(8):507–514. doi: 10.1038/s41577-020-0357-7

348. De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A, et al. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: A single-centre, prospective cohort study. Lancet Rheumatol. 2020;2(8):e465–e473. doi: 10.1016/S2665-9913(20)30170-3

349. Temesgen Z, Assi M, Shweta FNU, Vergidis P, Rizza SA, et al. GM-CSF neutralization with lenzilumab in severe COVID-19 pneumonia: A case-cohort study. Mayo Clin Proc. 2020;95(11):2382–2394. doi: 10.1016/j.mayocp.2020.08.038

350. Melody M, Nelson J, Hastings J, Propst J, Smerina M, Mendez J, et al. Case report: use of lenzilumab and tocilizumab for the treatment of coronavirus disease 2019. Immunotherapy. 2020;12(15):1121–1126. doi: 10.2217/imt-2020-0136

351. Crotti C, Agape E, Becciolini A, Biggioggero M, Favalli EG. Targeting granulocyte-monocyte colony-stimulating factor signaling in rheumatoid arthritis: Future prospects. Drugs. 2019;79(16):1741–1755. doi: 10.1007/s40265-019-01192-z

352. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1–S46. doi: 10.1016/j.jaci.2016.09.023

353. Nguyen AA, Habiballah SB, Platt CD, Geha RS, Chou JS, McDonald DR. Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution! Clin Immunol. 2020;216:108459. doi: 10.1016/j.clim.2020.108459

354. Herth FJF, Sakoulas G, Haddad F. Use of intravenous immunoglobulin (Prevagen or Octagam) for the treatment of COVID-19: Retrospective case series. Respiration. 2020;99(12):1145–1153. doi: 10.1159/000511376

355. Food and Drug Administration. Letter of authorization: EUA for baricitinib (Olumiant), in combination with remdesivir (Veklury), for the treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19). 2020. URL: https://www.fda.gov/media/143822/download (Accessed 11th December 2020).

356. Alunno A, Padjen I, Fanouriakis A, Boumpas DT. Pathogenic and therapeutic relevance of JAK/STAT signaling in systemic lupus erythematosus: integration of distinct inflammatory pathways and the prospect of their inhibition with an oral agent. Cells. 2019;8(8):898. doi: 10.3390/cells8080898

357. Анти-В-клеточная терапия в ревматологии: фокус на ритуксимаб. Под ред. ЕЛ Насонова. М.: ИМА-ПРЕСС;2012:119–152.

358. Mehta P, Porter JC, Chambers RC, Isenberg DA, Reddy V. B-cell depletion with rituximab in the COVID-19 pandemic: where do we stand? Lancet Rheumatol. 2020. doi: https://doi.org/10.1016/S2665-9913(20)30270-8

359. Loarce-Martos J, García-Fernández A, López-Gutiérrez F, García-García V, Calvo-Sanz L, et al. High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study. Rheumatol Int. 2020;40(12):2015–2021. doi: 10.1007/s00296-020-04699-x

360. Webb BJ, Peltan ID, Jensen P, et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome: A cohort study. Lancet Rheumatol. 2020;2(12):e754–e763. doi: 10.1016/S2665-9913(20)30343-X

361. Caricchio R, Gallucci M, Dass C; Temple University COVID-19 Research Group, et al. Preliminary predictive criteria for COVID-19 cytokine storm. Ann Rheum Dis. 2021;80(1):88–95. doi: 10.1136/annrheumdis-2020-218323

362. Lippi G, Plebani M. Cytokine «storm», cytokine «breeze», or both in COVID-19? Clin Chem Lab Med. 2020. doi: 10.1515/cclm-2020-1761

363. Martens RJH, van Adrichem AJ, Mattheij NJA, Brouwer CG, van Twist DJL, et al. Hemocytometric characteristics of COVID-19 patients with and without cytokine storm syndrome on the sysmex XN-10 hematology analyzer. Clin Chem Lab Med. 2020 Dec 8. doi: 10.1515/cclm-2020-1529

364. Sinha P, Calfee CS, Cherian S, et al. Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: A prospective observational study. Lancet Respir Med. 2020;8(12):1209–1218. doi: 10.1016/S2213-2600(20)30366-0

365. Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184(1):149-168.e17. doi: 10.1016/j.cell.2020.11.025

366. Liu Y, Zhang C, Huang F, et al. Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury. Natl Sci Rev. 2020;7(6):1003–1011. doi: 10.1093/nsr/nwaa037