J Korean Med Sci.  2021 Mar;36(12):e95. 10.3346/jkms.2021.36.e95.

COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology

• Park JK
• Lee EB
• Shin K
• Sung YK
• Kim TH
• Kwon SR
• Lee MS
• Hong SJ
• Choi BY
• Lee SS
• Back HJ
• on behalf of the Korean College of Rheumatology Task Force for COVID-19 Vaccine Guidance for Pat

• KMID: 2514128
• DOI: http://doi.org/10.3346/jkms.2021.36.e95

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1–2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.

Keyword

COVID-19; Autoimmune Inflammatory Rheumatic Diseases; Vaccines; Immunosuppression

Reference

1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239–1242. PMID: 32091533.

2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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. PMID: 32171076.

3. Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021; 184(4):861–880. PMID: 33497610.

4. Kim MJ, Lee EB, Song YW, Park JK. Profile of common inflammatory markers in treatment-naïve patients with systemic rheumatic diseases. Clin Rheumatol. 2020; 39(10):2899–2906. PMID: 32314175.

5. 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. PMID: 23836224.

6. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. Type I interferons in infectious disease. Nat Rev Immunol. 2015; 15(2):87–103. PMID: 25614319.

7. Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013; 52(1):53–61. PMID: 23192911.

8. Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002; 46(9):2287–2293. PMID: 12355475.

9. Hyrich KL, Machado PM. Rheumatic disease and COVID-19: epidemiology and outcomes. Nat Rev Rheumatol. 2021; 17(2):71–72. PMID: 33339986.

10. 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. Forthcoming. 2020; DOI: 10.1136/annrheumdis-2020-218946.

11. Emmi G, Bettiol A, Mattioli I, Silvestri E, Di Scala G, Urban ML, et al. SARS-CoV-2 infection among patients with systemic autoimmune diseases. Autoimmun Rev. 2020; 19(7):102575. PMID: 32376395.

12. Sarzi-Puttini P, Marotto D, Caporali R, Montecucco CM, Favalli EG, Franceschini F, et al. Prevalence of COVID infections in a population of rheumatic patients from Lombardy and Marche treated with biological drugs or small molecules: a multicentre retrospective study. J Autoimmun. 2021; 116:102545. PMID: 32972804.

13. Cordtz R, Lindhardsen J, Soussi BG, Vela J, Uhrenholt L, Westermann R, et al. Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark. Rheumatology (Oxford). 2020; keaa897. PMID: 33369663.

14. Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al. 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. PMID: 32471903.

15. Hasseli R, Mueller-Ladner U, Hoyer BF, Krause A, Lorenz HM, Pfeil A, et al. Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases. RMD Open. 2021; 7(1):e001464. PMID: 33479021.

16. Zucchi D, Tani C, Elefante E, Stagnaro C, Carli L, Signorini V, et al. Impact of first wave of SARS-CoV-2 infection in patients with Systemic Lupus Erythematosus: Weighting the risk of infection and flare. PLoS One. 2021; 16(1):e0245274. PMID: 33439910.

17. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020; 383(27):2603–2615. PMID: 33301246.

18. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021; 384(5):403–416. PMID: 33378609.

19. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021; 397(10269):99–111. PMID: 33306989.

20. Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021; 397(10275):671–681. PMID: 33545094.

21. Vaccines and related biological products advisory committee meeting. Updated 2021. Accessed February 13, 2021. https://www.fda.gov/media/146219/download.

22. Novavax creating tomorrow's vaccine today: announcement of UK and South Africa trial results. Updated 2021. Accessed February 13, 2021. https://www.novavax.com/sites/default/files/2021-01/UK-SouthAfrica-Trial-Results--FINAL.pdf.

23. Sinovac announces phase III results of its COVID-19 vaccine. Updated 2021. Accessed February 13, 2021. http://www.sinovac.com/?optionid=754&auto_id=922.

24. Rosenbaum L. Escaping catch-22 - overcoming Covid vaccine hesitancy. N Engl J Med. Forthcoming. 2021; DOI: 10.1056/NEJMms2101220.

25. Schwarzinger M, Watson V, Arwidson P, Alla F, Luchini S. COVID-19 vaccine hesitancy in a representative working-age population in France: a survey experiment based on vaccine characteristics. Lancet Public Health. Forthcoming. 2021; DOI: 10.1016/S2468-2667(21)00012-8.

26. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270–273. PMID: 32015507.

27. Brisse M, Vrba SM, Kirk N, Liang Y, Ly H. Emerging concepts and technologies in vaccine development. Front Immunol. 2020; 11:583077. PMID: 33101309.

28. Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Ebisawa M, El-Gamal Y, et al. COVID-19 vaccine-associated anaphylaxis: a statement of the World Allergy Organization Anaphylaxis Committee. World Allergy Organ J. 2021; 14(2):100517. PMID: 33558825.

29. Thacker EE, Timares L, Matthews QL. Strategies to overcome host immunity to adenovirus vectors in vaccine development. Expert Rev Vaccines. 2009; 8(6):761–777. PMID: 19485756.

30. Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. 2020; 383(24):2320–2332. PMID: 32877576.

31. Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021; 21(2):181–192. PMID: 33217362.

32. Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020; 383(25):2439–2450. PMID: 33053279.

33. Couch RB, Atmar RL, Franco LM, Quarles JM, Wells J, Arden N, et al. Antibody correlates and predictors of immunity to naturally occurring influenza in humans and the importance of antibody to the neuraminidase. J Infect Dis. 2013; 207(6):974–981. PMID: 23307936.

34. Schwarzkopf S, Krawczyk A, Knop D, Klump H, Heinold A, Heinemann FM, et al. Cellular immunity in COVID-19 convalescents with PCR-confirmed infection but with undetectable SARS-CoV-2-specific IgG. Emerg Infect Dis. 2021; 27(1):122–129.

35. Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021; 371(6529):eabf4063. PMID: 33408181.

36. Kapetanovic MC, Kristensen LE, Saxne T, Aktas T, Mörner A, Geborek P. Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis. Arthritis Res Ther. 2014; 16(1):R2. PMID: 24383620.

37. Bingham CO 3rd, Rizzo W, Kivitz A, Hassanali A, Upmanyu R, Klearman M. Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA). Ann Rheum Dis. 2015; 74(5):818–822. PMID: 24448345.

38. Jovani V, Calabuig I, Peral-Garrido ML, Tovar-Sugrañes E, López-González MD, Bernabeu P, et al. Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors. Ann Rheum Dis. Forthcoming. 2020; DOI: 10.1136/annrheumdis-2020-218152.

39. Inoue S, Shibata Y, Takabatake N, Igarashi A, Abe S, Kubota I. Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases. EXCLI J. 2013; 12:760–765. PMID: 26600737.

40. Fischer L, Gerstel PF, Poncet A, Siegrist CA, Laffitte E, Gabay C, et al. Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases--a longitudinal study. Arthritis Res Ther. 2015; 17(1):151. PMID: 26048579.

41. Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020; 79(1):39–52. PMID: 31413005.

42. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016; 68(1):1–26.

43. Park JK, Lee MA, Lee EY, Song YW, Choi Y, Winthrop KL, et al. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2017; 76(9):1559–1565. PMID: 28468794.

44. Park JK, Lee YJ, Shin K, Ha YJ, Lee EY, Song YW, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018; 77(6):898–904. PMID: 29572291.

45. Park JK, Choi Y, Winthrop KL, Song YW, Lee EB. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial. Ann Rheum Dis. 2019; 78(9):1283–1284. PMID: 30904830.

46. Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020; 370:m2980. PMID: 32732190.

47. Freites Nuñez DD, Leon L, Mucientes A, Rodriguez-Rodriguez L, Font Urgelles J, Madrid García A, et al. Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020; 79(11):1393–1399. PMID: 32769150.

48. Hua C, Barnetche T, Combe B, Morel J. Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2014; 66(7):1016–1026. PMID: 24339395.

49. Winthrop KL, Mariette X. To immunosuppress: whom, when and how? That is the question with COVID-19. Ann Rheum Dis. 2020; 79(9):1129–1131. PMID: 32753413.

50. Webb LM, Walmsley MJ, Feldmann M. Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimulatory pathway: requirement for both B7-1 and B7-2. Eur J Immunol. 1996; 26(10):2320–2328. PMID: 8898940.

51. Alten R, Bingham CO 3rd, Cohen SB, Curtis JR, Kelly S, Wong D, et al. Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept. BMC Musculoskelet Disord. 2016; 17(1):231. PMID: 27229685.

52. Crnkic Kapetanovic M, Saxne T, Jönsson G, Truedsson L, Geborek P. Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis. Arthritis Res Ther. 2013; 15(5):R171. PMID: 24286269.

53. Westra J, van Assen S, Wilting KR, Land J, Horst G, de Haan A, et al. Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients. Clin Exp Immunol. 2014; 178(1):40–47. PMID: 24889761.

54. Baker D, Roberts CA, Pryce G, Kang AS, Marta M, Reyes S, et al. COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin Exp Immunol. 2020; 202(2):149–161. PMID: 32671831.

55. Winthrop KL, Silverfield J, Racewicz A, Neal J, Lee EB, Hrycaj P, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016; 75(4):687–695. PMID: 25795907.

56. Bronte V, Ugel S, Tinazzi E, Vella A, De Sanctis F, Canè S, et al. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J Clin Invest. 2020; 130(12):6409–6416. PMID: 32809969.

57. Santos CS, Férnandez XC, Moriano Morales C, Álvarez ED, Álvarez Castro C, López Robles A, et al. Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe? RMD Open. 2021; 7(1):e001439. PMID: 33455920.

58. Randolph HE, Barreiro LB. Herd immunity: understanding COVID-19. Immunity. 2020; 52(5):737–741. PMID: 32433946.

59. Seo YB, Moon SJ, Jeon CH, Song JY, Sung YK, Jeong SJ, et al. The practice guideline for vaccinating Korean patients with autoimmune inflammatory rheumatic disease. Infect Chemother. 2020; 52(2):252–280. PMID: 32618150.

60. Seo MR, Kim JW, Park EJ, Jung SM, Sung YK, Kim H, et al. Recommendations for the management of patients with systemic rheumatic diseases during the coronavirus disease pandemic. Korean J Intern Med. 2020; 35(6):1317–1332. PMID: 32972125.

61. Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Engl J Med. 2021; 384(7):643–649. PMID: 33378605.

62. Banerji A, Wickner PG, Saff R, Stone CA Jr, Robinson LB, Long AA, et al. mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach. J Allergy Clin Immunol Pract. Forthcoming. 2020; DOI: 10.1016/j.jaip.2020.12.047.