The course and outcomes of COVID-19 in patients with ANCA-associated systemic vasculitis, receiving biological therapy (Rituximab, Mepolizumab): The results of the first 8 months of the pandemic
https://doi.org/10.47360/1995-4484-2021-37-46
Abstract
Objective. Currently, the issues of the effect of anti-B cell therapy or inhibitor of interleukin 5 on the risk of COVID-19 infecting and outcomes in patients with ANCA-associated vasculitis (AAV) has not been completely studied. We present an analysis of the COVID-19 course and outcomes in AAV patients treated with rituximab or mepolizumab from one rheumatology center registry.
Methods. From November 11 to November 15, 2020, a cross-sectional study was conducted using telephone and online surveys, and information was collected from all 128 AAV patients treated with rituximab in V.A. Nasonova Research Institute of Rheumatology. Patients mean age was 51 (20–81) years, 61.7% were women. Granulomatosis with polyangiitis (GPA) was diagnosed in 58 patients, microscopic polyangiitis (MPA) – in 38, eosinophilic granulomatosis with polyangiitis (EGPA) – in 24 (including 54.2% of ANCA-negative cases), and AAV with uncertain nosological affiliation – in 8 patients. Due to the disease activity or a high risk of AAV recurrence during the pandemic rituximab was prescribed in 60/126 (47.6%) patients, and mepolizumab – in 6 cases.
Results. In the spring of the pandemic (until May 2020), the incidence of COVID-19 in AAV patients treated with rituximab was 4.3%, the disease course was relatively favorable. All patients recovered. At month 3–6, antibodies to SARS-CoV-2 IgG persisted in only 1 out of 4 patients. Since September 2020, the incidence has increased 3-fold, with a more severe course of COVID-19. In total, in the period until November 11, 2020, COVID-19 was diagnosed in 17.2% (22/128); the mean age of patients was 55 (25–81) years; 54.5% were women. 21/22 patients were on rituximab therapy, 2 patients had mepolizumab therapy (including 1 case after previous rituximab therapy). COVID-19 incidence was lower in patients with GPA (15.5%) vs MPA and EGPA (21.1% and 20.8% respectively). The mortality rate was 13.6%, including 2 patients with MPA and 1 patient with GPA. When analyzing the 5-year survival rate according to the registry of AAV patients treated with rituximab, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years – only 2 deaths.
Discussion. Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (primarily in the context of microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome as manifestation of the acute inflammatory syndrome), the activity of AAV can potentially contribute to the disease onset and a severe course of COVID-19. Given the previously published information on the use of rituximab during the COVID-19 pandemic for various diseases, it seems that B cell depletion, without reducing the risk of infection, may have a protective effect with regard to the risk of severe/catastrophic COVID-19, which, however, can be insufficient in AAV patients. Further analysis of COVID-19 cases in patients with AAV and other immuno-inflammatory rheumatic diseases is exceptionally important.About the Authors
T. V. BeketovaRussian Federation
Tatiana Beketova
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests: нет
V. V. Babak
Russian Federation
Valeriya V. Babak
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests: нет
M. D. Suprun
Russian Federation
Marina D. Suprun
115522, Moscow, Kashirskoye Highway, 34A
Competing Interests: нет
References
1. Nasonov EL, Lila AM, Mazurov VI, Belov BS, Karateev AE, Dubinina TV, et al. Coronavirus disease 2019 (COVID-19) and immune inflammatory (autoimmune) rheumatic diseases. Draft recommendations of the All-Russian public organization Association of rheumatologists of Russia. 2020 (In Russ.). URL: https://rheumatolog.su/news/koronavirusnaya-bolezn-2019-COVID-19-i-immunovospalitelnye-autoimmunnye-revmaticheskie-zabolevaniya/ (accessed: 2020)
2. Beketova TV. Diagnostic algorithm for antineutrophil cytoplasmic antibody-associated systemic vasculitis. Terapevticheskiy arkhiv = Therapeutic Archive. 2018;5:13–21 (In Russ.). doi: 10.26442/terarkh201890513-21
3. Fornasari PM. COVID-19: Neutrophils “unfriendly fire” imbalance proteolytic cascades triggering clinical worsening and viral sepsis. Potential role explanation for convalescent plasma as “fire hose”. Preprints. 2020;2020050373. doi: 10.20944/preprints202005.0373.v1
4. Luqmani R, Suppiah R, Edwards CJ, Phillip R, Maskell J, Culliford D, et al. Mortality in Wegener’s granulomatosis: A bimodal pattern. Rheumatology (Oxford, England). 2011;50(4): 697–702. doi: 10.1093/rheumatology/keq351
5. Colling ME, Kanthi Y. COVID-19-associated coagulopathy: An exploration of mechanisms. Vascular Medicine. 2020;25(5):471– 478. doi: 10.1177/1358863X20932640
6. Ciceri F, Beretta L, Scandroglio AM, Colombo S, Landoni G, Ruggeri A, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): An atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020;22(2):95–97.
7. Nasonov EL, Beketova TV, Reshetnyak TM, Lila AM, Ananieva LP, Lisitsyna TA, et al. Coronavirus disease 2019 (COVID-19) and immune-mediated inflammatory rheumatic diseases: At the crossroads of thromboinflammation and autoimmunity. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2020;58(4):353–367 (In Russ.). doi: 10.47360/1995-4484-2020-353-367
8. Zabozlaev FG, Kravchenko EV, Gallyamova AR, Letunovsky NN. Pulmonary pathology of the new coronavirus disease (COVID-19). The preliminary analysis of post-mortem findings. Klinicheskaya praktika = Journal of Clinical Practice. 2020;11(2):21–37 (In Russ.). doi: 10.17816/clinpract34849
9. Kronbichler A, Lee KH, Denicolò S, Choi D, Lee H, Ahn D, et al. Immunopathogenesis of ANCA-associated vasculitis. Int J Mol Sci. 2020;21(19):7319. doi: 10.3390/ijms21197319
10. Talotta R, Robertson E. Autoimmunity as the comet tail of COVID-19 pandemic. World J Clin Cases. 2020;8(17):3621– 3644. doi: 10.12998/wjcc.v8.i17.3621
11. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020;71(16):2027–2034. doi: 10.1093/cid/ciaa344
12. Woodruff MC, Ramonell RP, Cashman KS, Nguyen DC, Saini AS, Haddad N, et al. Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation. medRxiv. 2020.04.29.20083717; doi: 10.1101/2020.04.29.20083717
13. Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID-19. Nat Rev Immunol. 2020;20:339–341. doi: 10.1038/s41577-020-0321-6
14. Wang Y, Zhang L, Sang L, Ye F, Ruan S, Zhong B, et al. Kinetics of viral load and antibody response in relation to COVID-19 severity. J Clin Invest. 2020;130(10):5235–5344. doi: 10.1172/JCI138759
15. Sun B, Feng Y, Mo X, et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):940–948. doi: 10.1080/22221751.2020.1762515
16. Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. doi: 10.1126/science.abd4585
17. Song WC, FitzGerald GA. COVID-19, microangiopathy, hemostatic activation, and complement. J Clin Invest. 2020;130(8): 3950–3953. doi: 10.1172/JCI140183
18. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, 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
19. Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z, et al. Heightened Innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27:883–890.e2 doi: 10.1016/j.chom.2020.04.017
20. Singh A, Sood N, Narang V, Goyal A. Morphology of COVID-19-affected cells in peripheral blood film. BMJ Case Rep. 2020;13(5):e236117. doi: 10.1136/bcr-2020-236117
21. Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17(5):533–535. doi: 10.1038/s41423-020-0402-2
22. Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020;20:269–270. doi: 10.1038/S41577-020-0308-3
23. Sachdeva M, Gianotti R, Shah M, Bradanini L, Tosi D, Veraldi S, et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J Dermatol Sci. 2020;98:75–81. doi: 10.1016/j.jdermsci.2020.04.011
24. Conde Cardona G, Quintana Pájaro LD, Quintero Marzola ID, Ramos Villegas Y, Moscote Salazar LR. Neurotropism of SARS-CoV-2: Mechanisms and manifestations. J Neurol Sci. 2020;412:116824. doi: 10.1016/j.jns.2020.116824
25. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: Causality or coincidence? Lancet Neurol. 2020;19:383–384. doi: 10.1016/S1474-4422(20)30109-5
26. Lazarian G, Quinquenel A, Bellal M, Siavellis J, Jacquy C, Re D, et al. Autoimmune haemolytic anaemia associated with COVID-19 infection. Br J Haematol. 2020;190:29–31. doi: 10.1111/bjh.16794
27. Zulfiqar AA, Lorenzo-Villalba N, Hassler P, Andrès E. Immune thrombocytopenic purpura in a patient with Covid-19. N Engl J Med. 2020;382:e43. doi: 10.1056/NEJMc2010472
28. Beydon M, Chevalier K, Al Tabaa O, Hamroun S, Delettre AS, Thomas M, et al. Myositis as a manifestation of SARS-CoV-2. Ann Rheum Dis. Published Online First. 2020. doi: 10.1136/annrheumdis-2020-217573
29. Craver R, Huber S, Sandomirsky M, McKenna D, Schieffelin J, Finger L. Fatal eosinophilic myocarditis in a healthy 17-year-old male with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2c). Fetal Pediatr Pathol. 2020;39:263–268. doi: 10.1080/1551 3815.2020.1761491
30. Andina D, Noguera-Morel L, Bascuas-Arribas M, Gaitero-Tristán J, Alonso-Cadenas JA, Escalada-Pellitero S, et al. Chilblains in children in the setting of COVID-19 pandemic. Pediatr Dermatol. 2020;37:406–411. doi: 10.1111/pde.14215
31. Licciardi F, Pruccoli G, Denina M, Parodi E, Taglietto M, Rosati S, et al. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: A novel COVID phenotype in children. Pediatrics. 2020;146:e20201711. doi: 10.1542/peds.2020-1711
32. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. Lancet. 2020;395:1771–1778. doi: 10.1016/S0140-6736(20)31103-X
33. 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
34. Letellier A, Gibelin A, Voiriot G, Fartoukh M, Djibré M. Destructive pulmonary fibrosis after severe COVID-19 pneumonia. Int J Infect Dis. 2020;100:377–378. doi: 10.1016/j.ijid.2020.09.026
35. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The perspectives of clinical immunologists from China. Clin Immunol. 2020;214:108393. doi: 10.1016/j.clim.2020.108393
36. Guisado-Vasco P, Valderas-Ortega S, Carralón-González MM, Roda-Santacruz A, González-Cortijo L, Sotres-Fernández G, et al. Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort). EClinicalMedicine. 2020;28:100591. doi: 10.1016/j.eclinm.2020.100591
37. Diurno F, Numis FG, Porta G, Cirillo F, Maddaluno S, Ragozzino A, 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
38. Nasonov EL, Beketova TV, Ananyeva LP, Vasilyev VI, Solovyev SK, Avdeeva AS. Prospects for anti-B-cell therapy in immuno-inflammatory rheumatic diseases. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2019;57:1–40 (In Russ.). doi: 10.14412/1995-4484-2019-3-40
39. Izquierdo JL, Almonacid C, González Y, Del Rio-Bermúdez C, Ancochea J, Cárdenas R, et al. The impact of COVID-19 on patients with asthma. Eur Respir J. Published online ahead of print. 2020 Dec 17;2003142. doi: 10.1183/13993003.03142-2020
40. Matucci A, Caminati M, Vivarelli E, Vianello A, Micheletto C, Menzella F, et al. COVID-19 in severe asthmatic patients during ongoing treatment with biologicals targeting type 2 inflammation: Results from a multicenter Italian survey. Allergy. 2020. doi: 10.1111/all.14516
41. Banerjee S, George M, Young K, Venkatachalam S, Gordon J, Burroughs C, et al. Effects of the COVID-19 pandemic on patients living with vasculitis. ACR Open Rheumatology. 2020:1–8. doi: 10.1002/acr2.11204
42. Kant S, Morris A, Ravi S, Floyd L, Gapud E, Antichos B, et al. The impact of COVID-19 pandemic on patients with ANCA associated vasculitis. J Nephrol. 2020 Oct 8:1–6. doi: 10.1007/s40620-020-00881-3
43. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H, et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019;4:e123158. doi: 10.1172/jci.insight.123158
44. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19. medRxiv. 2020:2020.04.09.20059626. doi: 10.1101/2020.04.09.20059626
45. 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
46. Quinti I, Lougaris V, Cinzia Milito C, Cinetto F, Pecoraro A, Mezzaroma I, et al. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia. J All Clin Immunol. 2020;146(1):211–213.e4. doi: 10.1016/j.jaci.2020.04.013
47. Soresina A, Moratto D, Chiarini M, Paolillo C, Baresi G, Focà E, et al. Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover. Pediatr Allergy Immunol. 2020;31(5):565–569. doi: 10.1111/pai.13263
48. Fill L, Hadney L, Graven K, Persaud R, Hostoffer R. The clinical observation of a patient with common variable immunodeficiency diagnosed as having coronavirus disease 2019. Ann Allergy Asthma Immunol. 2020;125(1):112–114. doi: 10.1016/j.anai.2020.04.033
49. Montero-Escribano P, Matías-Guiu J, Gómez-Iglesias P, Porta-Etessam J, Pytel V, Matias-Guiu JA. Anti-CD20 and Covid-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain. Mult Scler Relat Disord. 2020;42:102185. doi: 10.1016/j.msard.2020.102185
50. Safavi F, Nourbakhsh B, Azimi AR. B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult Scler Relat Disord. 2020;43:102195. doi: 10.1016/j.msard.2020.102195
51. Schramm MA, Venhoff N, Wagner D, Thiel J, Huzly D, Craig-Mueller N, et al. COVID-19 in a severely immunosuppressed patient with life-threatening eosinophilic granulomatosis with polyangiitis. Front Immunol. 2020;11:2086. doi: 10.3389/fimmu.2020.02086
52. Suárez-Díaz S, Morán-Castaño C, Coto-Hernández R, et al. Mild COVID-19 in ANCA-associated vasculitis treated with rituximab. Ann Rheum Dis. Published Online First. 2020 Aug 7 doi: 10.1136/annrheumdis-2020-218246
53. Fallet B, Kyburz D, Walker UA. Mild course of Coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B-cells due to treatment with rituximab. Arthritis Rheumatol. 2020;72:1581–1582. doi: 10.1002/art.41380
54. Guilpain P, Le Bihan C, Foulongne V, Taourel P, Pansu N, Thibault A, et al. Rituximab for granulomatosis with polyangiitis in the pandemic of COVID-19: Lessons from a case with severe pneumonia. Ann Rheum Dis. 2021;80:e10. doi: 10.1136/annrheumdis-2020-217549
55. Loarce-Martos J, García-Fernández A, López-Gutiérrez F, García-García V, Calvo-Sanz L, del Bosque-Granero I, 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
56. Favalli EG, Agape E, Caporali R. Incidence and clinical course of COVID-19 in patients with connective tissue diseases: A descriptive observational analysis. J Rheumatol. 2020;47:1296. doi: 10.3899/jrheum.200507
Review
For citations:
Beketova T.V., Babak V.V., Suprun M.D. The course and outcomes of COVID-19 in patients with ANCA-associated systemic vasculitis, receiving biological therapy (Rituximab, Mepolizumab): The results of the first 8 months of the pandemic. Rheumatology Science and Practice. 2021;59(1):37-46. https://doi.org/10.47360/1995-4484-2021-37-46