Коронавирусная болезнь 2019 (COVID-19) и иммуновоспалительные ревматические заболевания: на перекрестке проблем тромбовоспаления и аутоиммунитета

Воспаление и свертывание крови составляют основу защиты организма от потенциально патогенных механических и биологических воздействий внешней и внутренней среды. Неконтролируемое воспаление приводит к гиперкоагуляции, подавлению антикоагуляции и нарушению процессов, контролирующих разрешение (resolution) воспаления, а образование «прокоагулянтных» медиаторов (тромбин, тканевой фактор и др.), активация тромбоцитов и клеток эндотелия сосудов (ЭК) поддерживает развитие воспаления. Все это, вместе взятое, составляет основу гетерогенного по своей природе патологического процесса, получившего название «тромбовоспаление» (thromboinflammation), или «иммунотромбоз» (immunothrombosis). В настоящее время «тромбовоспаление» в широком смысле слова рассматривается как универсальный патогенетический механизм многих широко распространенных острых и хронических заболеваний, в том числе иммуновоспалительных (аутоиммунных) ревматических заболеваний (ИВРЗ), нередко осложняющихся тяжелым, необратимым повреждением жизненно важных внутренних органов. Интерес к проблеме тромбовоспаления особенно возрос в период пандемии коронавирусной болезни 2019 (coronavirus disease 2019; СOVID-19), связанной с вирусом SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). В настоящее время тяжелый COVID-19 рассматривается как системный «тромбовоспалительный» синдром, получивший предварительное название COVID-19-ассоциированная коагулопатия, проявляющаяся развитием микро- и макроcосудистых тромбозов венозного и артериального русла. Обсуждаются общие патогенетические механизмы коагулопатии при COVID-19 и ИВРЗ, связанные с «дисрегуляцией» синтеза «провоспалительных» цитокинов, активацией системы комплемента, гиперпродукцией антифосфолипидных антител (аФЛ), и др. Гипотетически выделяется «аутоиммунный» субтип тромбовоспаления, идентификация генетических факторов (например, гены системы комплемента и др.) которых могут быть связаны с риском развития COVID-19-коагулопатии. Знания, накопленные в ревматологии в отношении механизмов развития тромбовоспаления при ИВРЗ и их фармакотерапии, будут способствовать разработке более эффективной, персонифицированной стратегии лечения COVID-19. 

1. Goeijenbier M, van Wissen M, van de Weg C, Jong E, Gerdes VE, et al. Viral infections and mechanisms of thrombosis and bleeding. J Med Virol. 2012; 84(10):1680-96. doi: 10.1002/jmv.23354

2. 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 3. Karbach S, Lagrange J, Wenzel P. Thromboinflammation and Vascular Dysfunction. Hamostaseologie. 2019; 39(2):180-187. doi: 10.1055/s-0038-1676130

3. Palankar R, Greinacher A. Challenging the concept of immunothrombosis. Blood. 2019; 133(6):508-509. doi: 10.1182/blood2018-11-886267

4. Frantzeskaki F, Armaganidis A, Orfanos SE. Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation. Respiration. 2017; 93(3):212-225. doi: 10.1159/000453002

5. Becatti M, Emmi G, Bettiol A, Silvestri E, Di Scala G, et al. Behçet’s syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects. Clin Exp Immunol. 2019; 195(3): 322–333. doi: 10.1111/cei.13243

6. Emmi G, Becatti M, Bettiol A, Hatemi G, Prisco D, Fiorillo C. Behçet’s Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils. Front Immunol. 2019; 10:1085. doi:10.3389/fimmu.2019.01085

7. Tamaki H, Khasnis A. Venous thromboembolism in systemic autoimmune diseases: A narrative review with emphasis on primary systemic vasculitides. Vasc Med. 2015; 20(4):369-76. doi: 10.1177/1358863X15573838

8. Emmi G, Silvestri E, Squatrito D, et al. Thrombosis in vasculitis: from pathogenesis to treatment. Thromb J. 2015;13:15. Published 2015 Apr 16. doi:10.1186/s12959-015-0047-z

9. Claudel SE, Tucker BM, Kleven DT, Pirkle JL Jr, Murea M. Narrative Review of Hypercoagulability in Small-Vessel Vasculitis. Kidney Int Rep. 2020;5(5):586-599. Published 2020 Jan 13. doi:10.1016/j.ekir.2019.12.018

10. Насонов ЕЛ, Решетняк ТМ, Алекберова ЗС. Тромботическая микроангиопатия в ревматологии: связь тромбовоспаления и аутоиммунитета. Терапевтический архив. 2020;92(5):4-14 doi: 10.26442/00403660.2020.05.000697

11. Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017; 129(21):2857-2863. doi: 10.1182/blood-2016-11-743104

12. Libby L, Loscalzo J, Ridker P, еt al. Inflammation, Immunity, and Infection in Atherothrombosis: JACC Review Topic of the Week. J Am Coll Cardiol. 2018; 72(17): 2071–2081. doi: 10.1016/j.jacc.2018.08.1043

13. Mitchell WB. Thromboinflammation in COVID-19 acute lung injury. Paediatric Respiratory Reviews (IF 2.615): 2020-06-11.doi: 10.1016/j.prrv.2020.06.004

14. Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020 Jun 11: 102597. doi: 10.1016/j.autrev.2020.102597

15. 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

16. 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

17. Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost. 2020;18(7):1559- 1561. doi:10.1111/jth.14849

18. Du F, Liu B, Zhang S. COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness [published online ahead of print, 2020 Jul 16]. J Thromb Thrombolysis. 2020;1-17. doi:10.1007/s11239-020-02224-2

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

20. Merrill JT, Erkan D, Winakur J, James JA. Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications. Nat Rev Rheumatol. 2020;1-9. doi:10.1038/s41584-020-0474-5

21. Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020; 22:95–97

22. Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020 May 26. doi: 10.1097/CCM.0000000000004458

23. Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020 May 15: 1–14. doi: 10.1007/s11239-020-02134-.

24. Joly RS, Siguret V, Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med. 2020 May 15 : 1–4. doi: 10.1007/s00134-020-06088-1

25. Tian W, Jiang W, Yao J, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020 May 22:10.1002/jmv.26050. doi: 10.1002/jmv.26050

26. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506:145-148. doi: 10.1016/j.cca.2020.03.022

27. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020; 191: 145–147.doi: 10.1016/j.thromres.2020.04.013

28. Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18:844–847. doi: 10.1111/jth.14768

29. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58(7):1116-1120. doi:10.1515/cclm-2020-0188

30. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432

31. Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed [published correction appears in Nat Rev Immunol. 2020 Jun 4]. Nat Rev Immunol. 2020; 20(7):389-391. doi:10.1038/s41577-020-0343-0

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

33. Goshua G, Pine AB, Meizlish ML, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020; 7(8):e575-e582. doi:10.1016/S2352-3026(20)30216-7

34. 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

35. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0

36. Pedersen SF, Ho YC. SARS-CoV-2: a storm is raging. J Clin Invest. 2020; 130(5):2202-2205. doi:10.1172/JCI137647

37. Henderson LA, Canna SW, Schulert GS, et al. On the Alert for Cytokine Storm: Immunopathology in COVID-19. Arthritis Rheumatol. 2020; 72(7):1059-1063. doi:10.1002/art.41285

38. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368(6490):473-474. doi:10.1126/science.abb8925

39. Behrens EM, Koretzky GA. Review: Cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheum. 2017; 69(6):1135-43. doi: 10.1002/art.40071

40. England JT, Abdulla A, Biggs CM, et al. Weathering the COVID19 storm: Lessons from hematologic cytokine syndromes [published online ahead of print, 2020 May 15]. Blood Rev. 2020;100707. doi:10.1016/j.blre.2020.100707

41. Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID19: Current State of the Science. Immunity. 2020;52(6):910-941. doi:10.1016/j.immuni.2020.05.002

42. Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013; 11:185. doi: 10.1186/1741-7015-11-185

43. Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?. Autoimmun Rev. 2020;19(7):102573. doi:10.1016/j.autrev.2020.102573

44. Fogarty H, Townsend L, Ni Cheallaigh C, et al. COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189(6):1044- 1049. doi:10.1111/bjh.16749

45. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46(4)):586–590. doi: 10.1007/s00134-020-05985-9

46. Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the ReninAngiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020; 126(10):1456-1474. doi: 10.1161/CIRCRESAHA.120.317015

47. Zheng Z, Peng F, Xu B, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020 Apr 23:S0163-4453(20)30234-6. doi: 10.1016/j.jinf.2020.04.021

48. Catanzaro M, Fagiani F, Racchi M, et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. 2020; 5: 84. doi: 10.1038/s41392-020-0191-1

49. 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

50. Савушкина НМ, Галушко EА, Демидова НВ, Гордеев АВ. Ангиотензины и ревматоидный артрит. Научнопрактическая ревматология. 2018;56(6):753-759. doi:10.14412/1995-4484-2018-753-759

51. Ranjbar R, Shafiee M, Hesari A, et al. The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases. J Cell Physiol. 2019; 234(3):2277-2295. doi: 10.1002/jcp.27205

52. Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int. 2020;98(2):314-322. doi:10.1016/j.kint.2020.05.013

53. Campbell CM, Kahwash R. Will Complement Inhibition Be the New Target in Treating COVID-19-Related Systemic Thrombosis?. Circulation. 2020;141(22):1739-1741. doi:10.1161/CIRCULATIONAHA.120.047419

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

55. Risitano AM, Mastellos DC, Huber-Lang M, et al. Complement as a target in COVID-19? [published correction appears in Nat Rev Immunol. 2020 Jul;20(7):448]. Nat Rev Immunol. 2020;20(6):343-344. doi:10.1038/s41577-020-0320-7

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

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

58. Gao T, Hu M, Zhang X, et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation. medRxiv. 2020.03.29.20041962. doi: 10.1101/2020.03.29.20041962

59. Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020;220:1-13. doi:10.1016/j.trsl.2020.04.007

60. Giani M, Seminati D, Lucchini A, Foti G, Pagni F. Exuberant Plasmocytosis in Bronchoalveolar Lavage Specimen of the First Patient Requiring Extracorporeal Membrane Oxygenation for SARS-CoV-2 in Europe. J Thorac Oncol. 2020;15(5):e65-e66. doi:10.1016/j.jtho.2020.03.008

61. Oku K, Nakamura H, Kono M, et al. Complement and thrombosis in the antiphospholipid syndrome. Autoimmun Rev. 2016; 15(10):1001-1004. doi:10.1016/j.autrev.2016.07.020

62. 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

63. Kotzen ES, Roy S, Jain K. Antiphospholipid Syndrome Nephropathy and Other Thrombotic Microangiopathies Among Patients With Systemic Lupus Erythematosus. Adv Chronic Kidney Dis. 2019; 26(5):376-386. doi: 10.1053/j.ackd.2019.08.012

64. Насонов ЕЛ. Антифосфолипидный синдром. Москва: Литтерра; 2004. 424 с. [Nasonov EL. Antifosfolipidnyi sindrom (Antiphospholipid syndrome). Moscow: Litterra; 2004. 424 p. (In Russ.)]

65. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018; 378(21):2010- 2021. doi: 10.1056/NEJMra1705454.

66. 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

67. Espinosa G, Rodríguez-Pintó I, Gomez-Puerta JA, Pons-Estel G, Cervera R; Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Relapsing catastrophic antiphospholipid syndrome potential role of microangiopathic hemolytic anemia in disease relapses. Semin Arthritis Rheum. 2013;42(4):417-23. doi: 10.1016/j.semarthrit.2012.05.005

68. 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

69. Chaturvedi S, Braunstein EM, Yuan X, et al. Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood. 2019;135(4):239-251. doi: 10.1182/blood.2019003863

70. Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020;382(17):e38. doi:10.1056/NEJMc2007575

71. Hossri S, Shadi M, Hamarsha Z, Schneider R, El-Sayegh D. Clinically significant anticardiolipin antibodies associated with COVID-19 [published online ahead of print, 2020 May 29]. J Crit Care. 2020;59:32-34. doi:10.1016/j.jcrc.2020.05.017

72. Sung J, Anjum S. Coronavirus Disease 2019 (COVID-19) Infection Associated With Antiphospholipid Antibodies and Four-Extremity Deep Vein thrombosis in a Previously Healthy Female. Cureus. 2020;12(6):e8408. Published 2020 Jun 2. doi:10.7759/cureus.8408

73. Sieiro Santos C, Nogal Arias C, Moriano Morales C, Ballesteros Pomar M, Diez Alvarez E, Perez Sandoval T. Antiphospholipid antibodies in patient with acute lower member ischemia and pulmonary thromboembolism as a result of infection by SARSCoV2. Clin Rheumatol. 2020;39(7):2105-2106. doi:10.1007/s10067-020-05194-1

74. Beyrouti R, Adams ME, Benjamin L, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(8):889-891. doi:10.1136/jnnp-2020-323586

75. Escher R, Breakey N, Lämmle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020;190:62. doi:10.1016/j.thromres.2020.04.014

76. Xiao M, Zhang Y, Zhang S, et al. Brief Report: Anti-phospholipid antibodies in critically ill patients with Coronavirus Disease 2019 (COVID-19). Arthritis Rheumatol. 2020; doi:10.1002/art.41425

77. Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with Covid-19. J Thromb Haemost. 2020;18(8):2064-2065. doi:10.1111/jth.14867

78. Bertin D, Brodovitch A, Beziane A, et al. Anti-cardiolipin IgG autoantibodies are an independent risk factor of COVID-19 severity [published online ahead of print, 2020 Jun 21]. Arthritis Rheumatol. 2020;10.1002/art.41409. doi:10.1002/art.41409

79. Previtali G, Seghezzi M, Moioli V, et al. The pathogenesis of thromboembolic disease in COVID-19 patients: could be catastrophic antiphospholipid syndrom? medRxiv 2020.04.30.20086397. doi: 10.1101/2020.04.30.20086397

80. Connell NT, Battinelli EM, Connors JM. Coagulopathy of COVID-19 and antiphospholipid antibodies [published online ahead of print, 2020 May 7]. J Thromb Haemost. 2020; doi:10.1111/jth.14893

81. Devreese KMJ, Linskens EA, Benoit D, Peperstraete H. Antiphospholipid antibodies in patients with COVID-19: A relevant observation?. J Thromb Haemost. 2020;10.1111/ jth.14994. doi:10.1111/jth.14994

82. Zhang Y, Cao W, Jiang W, et al. Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients. J Thromb Thrombolysis. 2020; 1-7. doi:10.1007/s11239-020-02182-9

83. Amezcua-Guerra LM, Rojas-Velasco G, Brianza-Padilla M, et al. Presence of antiphospholipid antibodies in COVID-19: case series study. Ann Rheum Dis. 2020; doi:10.1136/annrheumdis-2020-218100

84. Pineton de Chambrun M, Frere C, Miyara M, et al. High frequency of antiphospholipid antibodies in critically ill COVID19 patients: a link with hypercoagulability? J Intern Med. 2020;10.1111/joim.13126. doi:10.1111/joim.13126

85. Zuo Yu, Estes SK, Gandhi AA, et al. Prothrombotic antiphospholipid antibodies in COVID-19. medRxiv 2020.06.15.20131607; doi: https://doi.org/10.1101/2020.06.15.20131607

86. Mendoza-Pinto C, García-Carrasco M, Cervera R. Role of Infectious Diseases in the Antiphospholipid Syndrome (Including Its Catastrophic Variant). Curr Rheumatol Rep. 2018;20(10):62. doi:10.1007/s11926-018-0773-x

87. 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

88. Pignatelli P, Ettorre E, Menichelli D, et al. 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

89. Tsivgoulis G, Palaiodimou L, Katsanos AH, et al. Neurological manifestations and implications of COVID-19 pandemic. Ther Adv Neurol Disord. 2020;13. doi:10.1177/1756286420932036

90. Lai CC, Ko WC, Lee PI, Jean SS, Hsueh PR. Extra-respiratory manifestations of COVID-19. Int J Antimicrob Agents. 2020;56(2):106024. doi:10.1016/j.ijantimicag.2020.106024

91. Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermatol. 2020;83(2):700. doi:10.1016/j.jaad.2020.04.018

92. Llamas-Velasco M, Muñoz-Hernández P, Lázaro-González J, et al. Thrombotic occlusive vasculopathy in a skin biopsy from a livedoid lesion of a patient with COVID-19 [published online ahead of print, 2020 May 14]. Br J Dermatol. 2020; doi:10.1111/bjd.19222

93. Liu T, Gu J, Wan L, et al. “Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res Ther. 2020;22(1):33. doi:10.1186/s13075-020-2131-4

94. Mekinian A, Bourrienne MC, Carbillon L, et al. Nonconventional antiphospholipid antibodies in patients with clinical obstetrical APS: Prevalence and treatment efficacy in pregnancies. Semin Arthritis Rheum.2016;46(2):232–237. doi: 10.1016/j.semarthrit.2016.05.006

95. Oku K, Amengual O, Atsumi T. Antiphospholipid scoring: significance in diagnosis and prognosis. Lupus.2014; 23(12):1269–1272. doi: 10.1177/0961203314561284

96. Schouwers SME, Delanghe JR, Devreese KMJ. Lupus Anticoagulant (LAC) Testing in Patients With Inflammatory Status: Does C-reactive Protein Interfere With LAC Test Results? Thromb Res 2010;125(1):102-4. doi: 10.1016/j.thromres.2009.09.001

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

98. Bravo-Barrera J. Kourilovitch M. Galarza-Maldonado C. Neutrophil Extracellular Traps, Antiphospholipid Antibodies and Treatment. Antibodies (Basel). 2017; 6: 4. doi: 10.3390/antib6010004

99. Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):e138999. Published 2020 Jun 4. doi:10.1172/jci.insight.138999

100. Zuo Y, Zuo M, Yalavarthi S, et al. Neutrophil extracellular traps and thrombosis in COVID-19. medRxiv 2020.04. doi: 10.1101/2020.04.30.20086736

101. Yalavarthi S, Gould TJ, Rao AN, 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

102. Meng H, Yalavarthi S, Kanthi Y, 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.39938

103. 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

104. Smatti MK, Cyprian FS, Nasrallah GK, Al 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

105. Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020; 17(5):533-5. doi: 10.1038/s41423-020-0402-2

106. Zheng HY, Zhang M, Yang CX, et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020;17(5):541-543. doi: 10.1038/s41423-020-0401-3

107. Pender MP. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Autoimmune Dis. 2012: 189096. doi: 10.1155/2012/189096

108. 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

109. Wei YY, Wang RR, Zhang DW, et al. Risk factors for severe COVID-19: Evidence from 167 hospitalized patients in Anhui, China. J Infect. 2020;81(1):e89-e92. doi:10.1016/j.jinf.2020.04.010

110. Du RH, Liu LM, Yin W, et al. Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China. Ann Am Thorac Soc. 2020;17(7):839-846. doi:10.1513/AnnalsATS.202003-225OC

111. Argenziano MG, Bruce SL, Slater CL. Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series. medRxiv. 2020;2020 04.20.20072116

112. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study [published correction appears in BMJ. 2020 Mar 31;368:m1295]. BMJ. 2020;368:m1091. Published 2020 Mar 26. doi:10.1136/bmj.m1091

113. Wang L, He W, Yu X. Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up. J Infect. 2020;80(6):639-645. doi: 10.1016/j.jinf.2020.03.019

114. Zulfiqar AA, Lorenzo-Villalba N, Hassler P, Andres E. Immune thrombocytopenic purpura in a patient with Covid-19. N. Engl. J Med. 2020, 382, e43. doi: 10.1056/NEJMc2010472

115. Albiol N, Awol R, Martino R. Autoimmune thrombotic thrombocytopenic putpura (TTP) associated with COVID-19. Ann Hematol. 2020, 28 May, htts://doi.org/10.1007/s00277-020-04097-0

116. Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020;382(26):2574-2576. doi:10.1056/NEJMc2009191

117. Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19-triggered autoimmune neurologic disease: More to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e781. doi: 10.1212/NXI.0000000000000781

118. Lazarian G, Quinquenel A, Bellal M, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol. 2020;190(1):29-31. doi:10.1111/bjh.16794

119. Beydon M, Chevalier K, Al Tabaa O, et al. Myositis as a manifestation of SARS-CoV-2. Ann Rheum Dis. 2020. doi:10.1136/annrheumdis-2020-217573.

120. Allez M, Denis B, Bouaziz J-D, et al. Covid-19 related IgA vasculitis. Arthritis Rheum 2020. doi:10.1002/ART.41428

121. 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

122. Galeotti C, Bayry J. Autoimmune and inflammatory diseases following COVID-19. Nat Rev Rheumatol. 2020;16(8):413-414. doi:10.1038/s41584-020-0448-7

123. Gagiannis D, Steinestel J, Hackenbroch C, et al. COVID-19- induced acute respiratory failure: an exacerbation of organ-specific autoimmunity? medRxiv 2020.04.27.20077180; doi: https://doi.org/10.1101/2020.04.27.20077180

124. Didier K, Bolko L, Giusti D, et al. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians? Front Immunol. 2018;9:541. doi: 10.3389/fimmu.2018.00541

125. Gazzaruso C, Carlo Stella N, Mariani G, et al. High prevalence of antinuclear antibodies and lupus anticoagulant in patients hospitalized for SARS-CoV2 pneumonia. Clin Rheumatol. 2020;39(7):2095-2097. doi:10.1007/s10067-020-05180-7

126. Zhou Y, Han T, Chen J, et al. Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID-19. Clin Transl Sci. 2020; doi:10.1111/cts.12805

127. Atzeni F, Gerardi MC, Barilaro G, et al. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review. Expert Rev Clin Immunol. 2018;14(1):69-82. doi: 10.1080/1744666X.2018.1411190

128. Mira-Avendano I, Abril A, Burger CD, et al. Interstitial Lung Disease and Other Pulmonary Manifestations in Connective Tissue Diseases. Mayo Clin Proc. 2019; 94(2):309-325. doi:10.1016/j.mayocp.2018.09.002

129. Акулкина ЛА, Бровко МЮ, Шоломова ВИ, Янакаева АШ, Моисеев СВ. Интерстициальная пневмония с аутоиммунными признаками (ИПАП): мультидисциплинарный диагноз в пульмонологии и ревматологии. Клиническая фармакология и терапия. 2018;18 (27):5-10.

130. Graney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019; 16(5): 525–533. doi: 10.1513/AnnalsATS.201808-565CME.

131. 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

132. Becker MO, Kill A, Kutsche M, et al. Vascular Receptor Autoantibodies in Pulmonary Arterial Hypertension Associated with Systemic Sclerosis. Amer J Resp Crit Care Med 2014; 190(7), 808–817. 10.1164/rccm.201403-0442OC

133. Avouac J, Riemekasten G, Meune C, et al. 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

134. Kill A, Tabeling C, Undeutsch R, 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

135. İlgen U, Yayla ME, Düzgün N. Anti-angiotensin II type 1 receptor autoantibodies (AT1R-AAs) in patients with systemic sclerosis: lack of association with disease manifestations. Rheumatol Int. 2017; 37(4):593-598. doi: 10.1007/s00296-016- 3639-4

136. Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(23):2950- 2973. doi: 10.1016/j.jacc.2020.04.031

137. Unlu O, Erkan D. Catastrophic Antiphospholipid Syndrome: Candidate Therapies for a Potentially Lethal Disease. Annu Rev Med. 2017;68:287-296. doi: 10.1146/annurev-med-042915-102529

138. Tektonidou MG, Andreoli L, Limper M, Tincani A, Ward MM. Management of thrombotic and obstetric antiphospholipid syndrome: a systematic literature review informing the EULAR recommendations for the management of antiphospholipid syndrome in adults. RMD Open. 2019;5(1):e000924. doi: 10.1136/rmdopen-2019-000924

139. Shi C, Wang C, Wang H, et al. The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study. medRxiv. 2020.03.28.20046144; doi: https://doi.org/10.1101/2020.03.28.20046144

140. Wang J, Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): A case series. J Thromb Haemost. 2020;18(7):1752-1755. doi:10.1111/jth.14828

141. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155-66. doi: 10.1038/s41584-020-0372-x

142. Meyerowitz EA, Vannier AGL, Friesen MGN, et al. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J. 2020; 34(5):6027-6037. doi: 10.1096/fj.202000919

143. Sarma P, Kaur H, Kumar H, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis. J Med Virol. 2020; 92(7):776-785. doi: 10.1002/jmv.25898

144. Yu B, Li C, Chen P, et al. Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Sci China Life Sci. 2020 May 15:1-7. doi: 10.1007/s11427-020-1732-2

145. Membrillo de Novales FJ, Ramírez-Olivencia G, Estébanez M, Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study. 2020, 2020050057. doi: 10.20944/preprints202005.0057.v1

146. 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

147. Rand JH, Wu X-X, Quinn AS, 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. 10.1182/blood-2009-04-213520

148. Urbanski G, Caillon A, Poli C, 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

149. Miranda S, Billoir P, Damian L, 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

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

151. Schreiber K, Breen K, Parmar K, Rand JH, Wu XX, 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

152. 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

153. Fanouriakis A, Kostopoulou M, Alunno A, 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

154. 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 May 13;10.1111/1753-0407.13053. doi: 10.1111/1753-0407.13053

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

156. Veronese N, Demurtas J, Yang L, et al. Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature. Front Med (Lausanne). 2020 Apr 24;7:170. doi: 10.3389/fmed.2020.00170

157. Strehl C, Ehlers L, Gaber T, Buttgereit F. Glucocorticoids-allrounders tackling the versatile players of the immune system. Front Immunol. 2019;10:1744. doi: 10.3389/fimmu.2019.01744

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

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

160. Oray M, Abu Samra K, Ebrahimiadib N, et al. Long-term side effects of glucocorticoids. Expert Opin Drug Saf. 2016;15(4):457- 65. doi: 10.1517/14740338.2016.1140743

161. WHO. Clinical management of severe acute respiratory infection when novel coronavirus [nCoV] infection is suspected. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novelcoronavirus-[ncov]-infection-is-suspected (accessed 09.02.2020)

162. Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020; 180(7):1-11. doi:10.1001/jamainternmed.2020.0994

163. Zhou W, Liu Y, Tian D, et al. Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia. Signal Transduct Target Ther. 2020; 5(1):18. doi:10.1038/s41392-020-0127-9

164. Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther. 2020; 5(1):57. doi: 10.1038/s41392-020-0158-2

165. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020; 10.1056/NEJMoa2021436. doi:10.1056/NEJMoa2021436

166. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immun. 2017; 139:S1-46. doi: 10.1016/j.jaci.2016.09.023

167. Tenti S, Cheleschi S, Guidelli GM, Galeazzi M, Fioravanti A. Intravenous immunoglobulins and antiphospholipid syndrome: How, when and why? A review of the literature. Autoimmun Rev. 2016; 15(3):226-35. doi: 10.1016/j.autrev.2015.11.009

168. Prete M, Favoino E, Catacchio G, Racanelli V, Perosa F. SARSCoV-2 infection complicated by inflammatory syndrome. Could high-dose human immunoglobulin for intravenous use (IVIG) be beneficial?. Autoimmun Rev. 2020;19(7):102559. doi:10.1016/j.autrev.2020.102559

169. Xie Y, Cao S, Dong H, et al. Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19. J Infect. 2020; 81(2):318-356. doi:10.1016/j.jinf.2020.03.044

170. Cao W, Liu X, Bai T, et al. High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019. Open Forum Infect Dis. 2020; 7(3):ofaa102. doi:10.1093/ofid/ofaa102

171. Diez J-M, Romero C, Gajardo R. Currently available intravenous immunoglobulin (Gamunex®-C and Flebogamma® DIF) contains antibodies reacting against SARS-CoV-2 antigens. bioRxiv. 2020 Apr 07:029017. doi: 10.1101/2020.04.07.029017

172. Rojas M, Rodríguez Y, Monsalve DM, et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev. 2020; 19(7):102554. doi:10.1016/j.autrev.2020.102554

173. Насонов ЕЛ. Иммунофармакология и иммунофармакотерапия коронавирусной болезни 2019 (COVID-19): фокус на интерлейкин 6. Научно-практическая ревматология 2020;58(3):245-261. doi:10.14412/1995-4484-2020-245-261

174. Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID19-a systematic review of current evidence. Ecancermedicalscience. 2020; 14:1022. Published 2020 Mar 27. doi:10.3332/ecancer.2020.1022

175. 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):4040-7. doi: 10.26355/eurrev_202004_20875

176. 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; 215:108450. doi:10.1016/j.clim.2020.108450

177. Bekker P, Dairaghi D, Seitz L, et al. Characterization of pharmacologic and pharmacokinetic properties of CCX168, a potent and selective orally administered complement 5a receptor inhibitor, based on preclinical evaluation and randomized Phase 1 clinical study. PLoS One. 2016; 11:e0164646. doi: 10.1371/journal.pone.0164646

178. Jayne DRW, Bruchfeld AN, Harper L, et al; CLEAR Study Group. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2017; 28(9):2756-67. doi: 10.1681/ASN.2016111179

179. Kello N, Khoury LE, Marder G, Furie R, Zapantis E, Horowitz DL. Secondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: Case series and review of literature. Semin Arthritis Rheum. 2019; 49(1):74-83. doi: 10.1016/j.semarthrit.2018.11.005

180. Levi M. Tocilizumab for severe COVID-19: A promising intervention affecting inflammation and coagulation. Eur J Intern Med. 2020; 76: 21–22. doi: 10.1016/j.ejim.2020.05.018

181. Senchenkova EY, Russell J, Yildirim A, Granger DN, Gavins FN. A novel role of T cells and IL-6 in angiotensin-II induced microvascular dysfunction. Hypertension 2020; 73(4):829-838. doi:10.1161/HYPERTENSIONAHA.118.12286

182. 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

183. Dimopoulos G, de Mast Q, Markou N, et al. Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis. Cell Host Microbe. 2020; 28(1):117-123.e1. doi:10.1016/j.chom.2020.05.007

184. 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; doi:10.1002/art.41422

185. Ucciferri C, Auricchio A, Di Nicola M, et al. Canakinumab in a subgroup of patients with COVID-19. Lancet Rheumatol. 2020; 2 (8):e452-e454. doi: 10.1016/S2665-9913(20)30167-3

186. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017; 377(12):1119-1131. doi:10.1056/NEJMoa1707914

187. Насонов ЕЛ, Попкова ТВ. Противовоспалительная терапия атеросклероза – вклад и уроки ревматологии. Научнопрактическая ревматология. 2017; 55(5):465-473. doi:10.14412/1995-4484-2017-465-473

188. Ridker PM, Libby P, MacFadyen JG, et al. Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J. 2018;39(38):3499-3507. doi: 10.1093/eurheartj/ehy310

189. Burzynski LC, Humphry M, Pyrillou K, et al. The Coagulation and Immune Systems Are Directly Linked through the Activation of Interleukin-1α by Thrombin. Immunity. 2019; 50(4):1033- 1042.e6. doi: 10.1016/j.immuni.2019.03.003

190. Насонов ЕЛ, Бекетова ТВ, Ананьева ЛП, Васильев ВИ, Соловьев СК, Авдеева АС. Перспективы анти-В-клеточной терапии при иммуновоспалительных ревматических заболеваниях. Научно-практическая ревматология. 2019;57:1-40. doi: 10.14412/1995-4484-2019-3-40.

191. Woodruff M, Ramonell R, Cashman K, et al. Critically ill SARSCoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv 2020.04.29.20083717. doi: 10.1101/2020.04.29.20083717

192. Quinti I, Lougaris V, Milito C, et al. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia. J Allergy Clin Immunol. 2020; 146(1):211-213.e4. doi:10.1016/j.jaci.2020.04.013

193. Pecoraro A, Crescenzi L, Galdiero MR, et al. Immunosuppressive therapy with rituximab in common variable immunodeficiency. Clin Mol Allergy. 2019; 17:9. doi:10.1186/s12948-019-0113-3

194. George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020; 8(8):807-815. doi:10.1016/S2213-2600(20)30225-3

195. Spagnolo P, Balestro E, Aliberti S, et al. Pulmonary fibrosis secondary to COVID-19: a call to arms? Lancet Respir Med. 2020; 8(8):750-752. doi:10.1016/S2213-2600(20)30222-8

196. Duarte AC, Cordeiro A, Fernandes BM, et al. Rituximab in connective tissue disease-associated interstitial lung disease. Clin Rheumatol. 2019; 38(7):2001-2009. doi: 10.1007/s10067-019-04557-7

197. Turgutkaya A, Yavaşoğlu İ, Bolaman Z. Application of plasmapheresis for Covid-19 patients [published online ahead of print, 2020 Jun 8]. Ther Apher Dial. 2020; doi:10.1111/1744-9987.13536