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Letter
SARS CoV-2 infection among patients using immunomodulatory therapies
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  1. Kevin L Winthrop1,2,
  2. Amanda E Brunton1,
  3. Susan Beekmann3,
  4. Philip Polgreen3,
  5. John Baddley4,
  6. Kenneth G Saag5,
  7. Cassandra Calabrese6,
  8. Leonard Calabrese6,
  9. Philip C Robinson7,
  10. Zachary S Wallace8,
  11. Jeffrey R Curtis5
  12. the COVID-19 Study Team
    1. 1 School of Public Health, Oregon Health & Science University, Portland, Oregon, USA
    2. 2 Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, USA
    3. 3 Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    4. 4 Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA
    5. 5 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
    6. 6 Division of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA
    7. 7 Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia
    8. 8 Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    1. Correspondence to Kevin L Winthrop, School of Public Health, Oregon Health and Science University, Portland OR 97239, USA; winthrop{at}ohsu.edu

    http://dx.doi.org/10.1136/annrheumdis-2020-218580

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      The risk of coronavirus disease 2019 (COVID-19) and disease progression among patients using immunomodulatory therapy is unclear. Accordingly, we implemented an active surveillance project with USA/Canada Infectious Disease specialists via the Emerging Infections Network (EIN) to identify COVID-19 cases occurring in patients who use immunomodulatory therapy and to describe their clinical outcomes.

      EIN listserv members include 2396 infectious disease physicians in the USA/Canada linked via a moderated listserv. On 8 April via listserv, we requested reports of COVID-19 cases among patients receiving immunomodulatory therapy. Two weekly reminders were later sent and case reports were collected until 22 May. We collected information regarding patient demographics, COVID-19 test results, symptoms, hospitalisation details, complications, treatment, pre-existing conditions, concomitant therapies, and patient outcomes. We conducted descriptive analyses of these patient factors and compared differences between survivors and non-survivors. We grouped immunosuppressive therapies by class (table 1).

      View this table:
      Table 1

      COVID-19 outcomes among autoimmune patients receiving immunomodulatory therapy

      Thirty-eight physicians screened over 2500 COVID-19 cases from which 77 (3%) were identified using immunomodulatory drugs. Of these, 52% were female, median age of 60 years (range, 16–84) and 83.1% had autoimmune disease (rheumatoid arthritis (19, 24.7%), ulcerative colitis (5, 6.5%) and sarcoidosis (5, 6.5%) were most common). Comorbidities included hypertension (26, 33.8%), diabetes (19, 24.7%), underlying chronic kidney disease (11, 14.3%) and others. All patients had PCR-confirmed COVID-19. Symptoms included dyspnoea (70.1%), fever (68.8%) and cough (64.9%). At time of COVID-19 diagnosis, 31 (40%) were using biologic therapies including anti tumor necrosis factor (anti-TNF) therapies (n=16), rituximab (n=6), abatacept (n=2), tocilizumab (n=2) and other (n=5). Among those using non-biologics at baseline (46, 60%), the following therapies were in use: janus kinase (JAK) inhibitors (3, 6.5%), non-biologic disease-modifying antirheumatic drugs (DMARDs) (11, 24%), prednisone alone (5, 11%) or other (27, 59%). Among those who received anti-COVID-19 treatment (n=41), the most common treatment regimens included hydroxychloroquine (n=27), azithromycin (n=10) and/or tocilizumab (n=10). Overall, 63 (81.8%) patients were hospitalised, 27 (35.1%) required mechanical ventilation, 37 (48.1%) required ICU care and 9 (11.7%) died. Patients who died were slightly older (median 68 years vs 58 years) and similar with regard to comorbidities as those who survived. No patients taking anti-TNF therapy at baseline died (table 1).

      Like other early reports, our surveillance effort yielded few biologic or JAK inhibitor using patients severely ill with COVID-19. Certainly, a lower risk of exposure could help explain this (ie, those patients perceiving high risk are social distancing), but it is also possible these therapies are protective against severe outcomes. A rheumatology registry of over 600 COVID-19 patients with autoimmune disease observed that those using biologics, in particular anti-TNF therapy, were less likely to be hospitalised.1

      While the overall proportion of patients who died in this case series is higher than reported in the US general population,2 this would be expected given the likelihood that most COVID-19 cases being consulted on by ID physicians would be within the inpatient setting. While we identified only a small number of anti-TNF users, none of them died. TNF blockers could hypothetically inhibit innate antiviral responses with COVID-19 or predispose to secondary bacterial infection, although in animal models of viral pneumonia they can be protective, and among inflammatory bowel disease (IBD) COVID-19 patients, the clinical outcomes of those using TNF blockers have been observed to be comparable or better to those using non-biologic DMARDs.3 4 While JAK inhibitors decrease innate viral immunity and might potentially increase the risk of viral progression, we found only two tofacitinib and one upadicitinib patients and all three had complete recovery. This and other studies involve small numbers of patients, making further population-based studies necessary to understand the risk of DMARDs with COVID-19.

      Acknowledgments

      The author thanks Teresa Xu for supporting the development of this report by assisting with the literature search and formatting.

      References

      1. ↵
        1. COVID-19 Global Rheumatology Alliance
        . The global rheumatology community's response to the worldwide COVID-19 pandemic. Available: https://rheum-covid.org/ [Accessed 18 May 2020].
      2. ↵
      3. ↵
        2. Feldmann M ,
        3. Maini RN ,
        4. Woody JN , et al
        . Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet 2020;395:1407–9.doi:10.1016/S0140-6736(20)30858-8 pmid:http://www.ncbi.nlm.nih.gov/pubmed/32278362
        OpenUrlCrossRefPubMed
      4. ↵
        1. Coronavirus and IBD Reporting Database
        . SECURE-IBD Database - Surveillance Epidemiology of Coronavirus Under Research Exclusion. Available: https://covidibd.org/ [Accessed 18 May 2020].

      Footnotes

      • Handling editor Josef S Smolen

      • Twitter @CCalabreseDO, @philipcrobinson

      • Collaborators Members of the COVID-19 Study Team: P. Holland Alday, Oregon Health and Science University; Juzar Ali, Louisiana State University School of Medicine, New Orleans LA; Yousaf Ali, Mount Sinai West, NYC; Rebecca Berdel, University of Southern California; Adam Brady, Good Samaritan Hospital; Brian Bramson, UNC Chapel Hill; David Brieff, North Shore ID Consultants, Port Washington NY; Wun-ling Chang, Lo Jolla ID Institute, San Diego CA; Jonathan Cheah, UMass Memorial; Kerry Cleveland, University of Tennessee College of Medicine; Carey J. Field, Rheumatologists of White River Junction VAMC, VT; Christopher Graber, David Geffen School of Medicine at UCLA; Nicholas Hartog, Michigan State University; Guy El Helou, University of Florida, Gainesville; Leigh M. Howard, Vanderbilt University Medical Center, Vivek Kak, Patient Infection and Infusion Center, Jackson MI; Jonathan Kay, Univ. Massachusetts Medical Center; Takaaki Kobayashi, University of Iowa Medical Center; Rebecca Kumar, Northwestern University; Nancy Liu, UMass Memorial; Jose A. Lucar, University of Mississippi Medical Center; Anuj Malik, Ascension St John Medical Center, Tulsa OK; Shirin Mazumder, University of Tennessee Health Sciences Center; Anne O’Donnell, Georgetown University; Rachel Orscheln, Washington University; Anais Ovalle, Dartmouth; Christopher Palma, University of Rochester Medical Center; Debendra Pattanaik, Univ. Tennessee Health Center; Bryan Poole, UMass Memorial; Husain Poonawala, Lowell General Hospital, MA; Ayesha Rashid, St. Paul Infectious Disease Associates, St. Paul, Minnesota, Luis Marcos, Stony Brook University; Francis Riedo, Evergreen Health; Kairav Shah, Metro Infectious Disease Consultants, Stockbridge GA; Robert Striker, Univ Wisconsin-Madison; Marjorie Wongskhaluang, Infectious Disease Associates of Kansas City; Hanna Zembrzuska, University of Iowa.

      • Contributors All coauthors contributed to the creation of this letter in all aspects including data gathering, analysis, writing and critical revision of the manuscript.

      • Funding This publication was supported by Cooperative Agreement Number 1 U50 CK00477 funded by the Centers for Disease Control and Prevention, and by Award Number UL1TR002537 funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The author thanks Teresa Xu for supporting the development of this report by assisting with literature search and formatting.

      • Disclaimer The findings and conclusions presented in this manuscript are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention or the Department of Health and Human Services.

      • Competing interests KLW reports personal fees from Pfizer, AbbVie, Union Chimique Belge (UCB), Eli Lilly & Company, Galapagos, GlaxoSmithKline (GSK), Roche, Gilead and reports research grants from BMS, Pfizer outside the submitted work. AB and SB have no potential conflicts of interest. PP reports grants from Centers for Disease Control and Prevention, grants from National Center For Advancing Translational Sciences, during the conduct of the study; non-financial support from 3M, personal fees from Eli Lily, outside the submitted work. JB reports personal fees from Pfizer, Lilly, R-Pharm and Viela Bio outside the submitted work. KGS reports grants and personal fees from Amgen, personal fees from Sanofi/Genzyme, personal fees from Gilead, outside the submitted work. CC reports personal fees from AbbVie and is a member of the speakers’ bureau for Sanofi-Regeneron outside the submitted work. LC reports personal fees from Genentech, personal fees from GMS, personal fees from GSK, personal fees from AbbVie, personal fees from Janssen, personal fees from Sanofi, personal fees from Gilead, personal fees from Kiniksa, personal fees from UCB, outside the submitted work. PCR reports personal fees and non-financial support from Roche, personal fees from Abbvie, grants and personal fees from Janssen, grants and personal fees from Novartis, non-financial support from BMS, personal fees from Eli Lilly, personal fees from Pfizer, grants and personal fees from UCB, outside the submitted work. ZSW reports research grants from NIH/NIAMS (K23AR073334 and L30 AR070520) and Bristol-Myers Squibb outside the submitted work. JRC reports grants and personal fees from AbbVie, grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from Corrona, grants and personal fees from Eli Lilly, grants and personal fees from Janssen, grants and personal fees from Myriad, grants and personal fees from Pfizer, grants and personal fees from Regeneron, grants and personal fees from Roche, grants and personal fees from UCB, outside the submitted work.

      • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

      • Patient consent for publication Not required.

      • Ethics approval This project was approved by the University of Iowa Institutional Review Board, IRB ID #202 003 698.

      • Provenance and peer review Not commissioned; externally peer reviewed.