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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2020

01-12-2020 | Glucocorticoid | Research article

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis

Authors: Ennio Giulio Favalli, Serena Bugatti, Catherine Klersy, Martina Biggioggero, Silvia Rossi, Orazio De Lucia, Francesca Bobbio-Pallavicini, Antonella Murgo, Silvia Balduzzi, Roberto Caporali, Carlomaurizio Montecucco

Published in: Arthritis Research & Therapy | Issue 1/2020

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Abstract

Background

Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis.

Methods

The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated.

Results

The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04–1.44] to 3.20 [1.97–5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18–1.21] to 0.47 [0.46–0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed.

Conclusions

During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection.

Trial registration

Retrospectively registered. Not applicable.
Appendix
Available only for authorised users
Literature
1.
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):1054–62.PubMedPubMedCentralCrossRef
2.
Acter T, Uddin N, Das J, Akhter A, Choudhury TR, Kim S. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: a global health emergency. Sci Total Environ. 2020;730:138996.PubMedPubMedCentralCrossRef
3.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763–70.PubMedPubMedCentralCrossRef
4.
Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966.PubMedPubMedCentralCrossRef
5.
Minotti C, Tirelli F, Barbieri E, Giaquinto C, Donà D. How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review. J Inf Secur. 2020;81(1):e61–6.
6.
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;323(18):1824–36.PubMed
7.
Phua J, Weng L, Ling L, Egi M, Lim C-M, Divatia JV, et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med. 2020;8(5):506–17.PubMedPubMedCentralCrossRef
8.
Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020;368(6493):860–8.
9.
Giordano G, Blanchini F, Bruno R, Colaneri P, Filippo AD, Matteo AD, et al. Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy. Nat Med. 2020;26(6):855-60.
10.
Favalli EG, Ingegnoli F, Lucia OD, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmun Rev. 2020;19(5):102523.PubMedPubMedCentralCrossRef
11.
Sarzi-Puttini P, Giorgi V, Sirotti S, Marotto D, Ardizzone S, Rizzardini G, et al. COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol. 2020;38(2):337–42.PubMed
12.
Campochiaro C, Della-Torre E, Cavalli G, Luca GD, Ripa M, Boffini N, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. Eur J Intern Med. 2020;76:43–9.PubMedPubMedCentralCrossRef
13.
Cavalli G, Luca GD, Campochiaro C, Della-Torre E, Ripa M, Canetti D, 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):e325–31.PubMedPubMedCentralCrossRef
14.
Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;2020:01047.
15.
Tu Y-F, Chien C-S, Yarmishyn AA, Lin Y-Y, Luo Y-H, Lin Y-T, et al. A review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci. 2020;21(7):2657.PubMedCentralCrossRef
16.
17.
Coletto LA, Favalli EG, Caporali R. Psoriasis and psoriatic arthritis: how to manage immunosuppressants in COVID -19 days. Dermatol Ther. 2020;33(4):e13415.
18.
19.
20.
Doran MF, Pond GR, Crowson CS, O’Fallon WM, Gabriel SE. Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum. 2002;46(3):625–31.PubMedCrossRef
21.
Blumentals WA, Arreglado A, Napalkov P, Toovey S. Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study. BMC Musculoskelet Dis. 2012;13(1):158.CrossRef
22.
Tinsley A, Navabi S, Williams ED, Liu G, Kong L, Coates MD, et al. Increased risk of influenza and influenza-related complications among 140,480 patients with inflammatory bowel disease. Inflamm Bowel Dis. 2018;25(2):369–76.CrossRef
23.
Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. 2015;386(9990):258–65.PubMedPubMedCentralCrossRef
24.
Noreña I, Fernández-Ruiz M, Aguado JM. Viral infections in the biologic therapy era. Expert Rev Anti-Infect Ther. 2018;16(10):781–91.PubMedCrossRef
25.
Mackay IR, Rosen FS, Davidson A, Diamond B. Autoimmune diseases. New Engl J Med. 2001;345(5):340–50.CrossRef
26.
Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685–99.PubMedCrossRef
27.
Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, et al. ECCO guidelines on therapeutics in Crohn’s disease: medical treatment. J Crohns Colitis. 2020;14(1):4–22.PubMedCrossRef
28.
Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599–613.PubMedPubMedCentralCrossRef
29.
van der Heijde D, Ramiro S, Landewé R, Baraliakos X, den Bosch FV, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978–91.PubMedCrossRef
30.
Gossec L, Coates LC, de Wit M, Kavanaugh A, Ramiro S, Mease PJ, et al. Management of psoriatic arthritis in 2016: a comparison of EULAR and GRAPPA recommendations. Nat Rev Rheumatol. 2016;12(12):743–50.PubMedCrossRef
31.
Baumgart DC, Misery L, Naeyaert S, Taylor PC. Biological therapies in immune-mediated inflammatory diseases: can biosimilars reduce access inequities? Front Pharmacol. 2019;10:279.PubMedPubMedCentralCrossRef
32.
33.
34.
Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly P, et al. COVID-19 in immune-mediated inflammatory diseases - case series from New York. New Engl J Med. 2020;383(1):85–88.
35.
Michelena X, Borrell H, López-Corbeto M, López-Lasanta M, Moreno E, Pascual-Pastor M, et al. Incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs. Semin Arthritis Rheum. 2020;50(4):564–70.
36.
Monteleone G, Ardizzone S. Are patients with inflammatory bowel disease at increased risk for COVID-19 infection? J Crohns Colitis. 2020;14(9):1334–6.PubMedCrossRef
37.
D’Antiga L. Coronaviruses and immunosuppressed patients: the facts during the third epidemic. Liver Transplant. 2020;26(6):832–4.CrossRef
38.
Devaux CA, Rolain J-M, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020;55(5):105938.
39.
Mathian A, Mahevas M, Rohmer J, Roumier M, Cohen-Aubart F, Amador-Borrero B, et al. Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Ann Rheum Dis. 2020. https://​doi.​org/​10.​1136/​annrheumdis-2020-217566.
40.
Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020;383(6):517–25.PubMedCrossRef
41.
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. https://​doi.​org/​10.​1136/​annrheumdis-2020-217871.
42.
Dixon WG, Suissa S, Hudson M. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses. Arthritis Res Ther. 2011;13(4):R139.PubMedPubMedCentralCrossRef
43.
Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroid use. Rheum Dis Clin N Am. 2015;42(1):157–76 ix–x.CrossRef
44.
Fardet L, Petersen I, Nazareth I. Common infections in patients prescribed systemic glucocorticoids in primary care: a population-based cohort study. PLoS Med. 2016;13(5):e1002024.PubMedPubMedCentralCrossRef
45.
Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Pardo-Hernandez H, et al. Drug treatments for COVID-19: living systematic review and network meta-analysis. BMJ. 2020;370:m2980.PubMedCrossRef
46.
47.
Caporali R, Favalli EG. Managing patients with rheumatic conditions during the COVID-19 pandemic. BMJ. 2020;369:m1633.PubMedCrossRef
48.
Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76(6):1101–36.PubMedCrossRef
49.
Strand V, Ahadieh S, French J, Geier J, Krishnaswami S, Menon S, et al. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther. 2015;17(1):362.PubMedPubMedCentralCrossRef
50.
Favalli EG, Desiati F, Atzeni F, Sarzi-Puttini P, Caporali R, Pallavicini FB, et al. Serious infections during anti-TNFα treatment in rheumatoid arthritis patients. Autoimmun Rev. 2009;8(3):266–73.PubMedCrossRef
51.
Atzeni F, Sarzi-Puttini P, Sebastiani M, Panetta V, Salaffi F, Iannone F, et al. Rate of serious infections in spondyloarthropathy patients treated with anti-tumour necrosis factor drugs: a survey from the Italian registry GISEA. Clin Exp Rheumatol. 2019;37(4):649–55.PubMed
52.
Rutherford AI, Subesinghe S, Hyrich KL, Galloway JB. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77(6):905–10.PubMed
53.
Singh JA, Wells GA, Christensen R, Ghogomu ET, Maxwell LJ, MacDonald JK, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2:CD008794.
54.
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.
55.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.PubMedPubMedCentralCrossRef
56.
57.
58.
Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970–75.
59.
Capra R, Rossi ND, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, 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.PubMedPubMedCentralCrossRef
60.
Quartuccio L, Sonaglia A, McGonagle D, Fabris M, Peghin M, Pecori D, et al. Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care. J Clin Virology. 2020;129:104444.
61.
Colaneri M, Bogliolo L, Valsecchi P, Sacchi P, Zuccaro V, Brandolino F, et al. Tocilizumab for treatment of severe COVID-19 patients: preliminary results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms. 2020;8(5):695.PubMedCentralCrossRef
62.
Keyaerts E, Vijgen L, Maes P, Neyts J, Ranst MV. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323(1):264–8.PubMedPubMedCentralCrossRef
63.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71(15):732–9.PubMedCrossRef
64.
Mahévas M, Tran V-T, Roumier M, Chabrol A, Paule R, Guillaud C, et al. Clinical efficacy of hydroxychloroquine in patients with COVID-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ. 2020;369:m1844.PubMedPubMedCentralCrossRef
65.
Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA. 2020;323(24):2493–502.PubMedPubMedCentralCrossRef
66.
Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. New Engl J Med. 2020;382(25):2411–8.PubMedCrossRef
67.
Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Brito M, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open. 2020;3(4.23):e208857.PubMedCrossRef
68.
69.
70.
Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68(7):1100–4.PubMedCrossRef
71.
Clapham H, Hay J, Routledge I, Takahashi S, Choisy M, Cummings D, et al. Seroepidemiologic study designs for determining SARS-COV-2 transmission and immunity. Emerg Infect Dis. 2020;26(9):1978–86.PubMedPubMedCentralCrossRef
Metadata
Title
Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis
Authors
Ennio Giulio Favalli
Serena Bugatti
Catherine Klersy
Martina Biggioggero
Silvia Rossi
Orazio De Lucia
Francesca Bobbio-Pallavicini
Antonella Murgo
Silvia Balduzzi
Roberto Caporali
Carlomaurizio Montecucco
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02395-6

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