Immunosuppression may bear a higher risk for SARS-CoV-2 infection and severe COVID-19. But the story is not that simple. Neither is it clear what immunosuppression actually means, nor are the available data sufficient to draw any conclusion. We just don’t know enough. Nevertheless, some authors are trumpeting the news that there is an increased risk. A bad example? A systematic review and meta-analysis on 8 studies and 4007 patients came to the conclusion that “immunosuppression and immunodeficiency were associated with increased risk of severe COVID-19 disease, although the statistical differences were not significant” (Gao 2020). The authors also state that “in response to the COVID-19 pandemic, special preventive and protective measures should be provided.” There is null evidence for this impressive statement. The total number of patients with immunosuppression in the study was 39 (without HIV: 11!), with 6/8 studies describing less than 4 patients with different modalities of immunosuppression.
Despite the large absence of data, numerous viewpoints and guidelines have been published on how to manage immunosuppressed patients that may be more susceptible to acquire COVID-19 infection and develop severe courses. There are recommendations for intranasal corticosteroids in allergic rhinitis (Bousquet 2020), immunosuppressants for psoriasis and other cutaneous diseases (Conforti 2020, Torres 2020), rheumatic diseases (Favalli 2020, Figueroa-Parra 2020) or inflammatory bowel diseases (Kennedy 2020, Pasha 2020). The bottom line of these heroic attempts to balance the risk of immune-modifying drugs with the risk associated with active disease: what is generally needed, has to be done (or to be continued). Exposure prophylaxis is important.
However, several studies have indeed found evidence for deleterious effects of glucocorticoids, indicating that these drugs should be given with particular caution these days.
- In 600 COVID-19 patients with rheumatic diseases from 40 countries, multivariate-adjusted models revealed a prednisone dose ≥ 10 mg/day to be associated with higher odds of hospitalization. There was no risk with conventional disease-modifying anti-rheumatic drugs (DMARD) alone or in combination with biologics and Janus kinase (JAK) inhibitors (https://doi.org/10.1136/annrheumdis-2020-217871).
- In 525 patients with inflammatory bowel disease (IBD) from 33 countries (Brenner 2020), risk factors for severe COVID-19 included systemic corticosteroids (adjusted odds ratio 6,9, 95% CI: 2,3-20,5), and sulfasalazine or 5-aminosalicylate use (aOR 3,1). TNF antagonist treatment was not associated with severe COVID-19.
- In 86 patients with IBD and symptomatic COVID-19, among them 62 receiving biologics or JAK inhibitors, hospitalization rates were higher in patients treated with oral glucocorticoids, hydroxychloroquine and methotrexate but not with JAK inhibitors (Haberman 2020).
- In a large French database, including patients with inflammatory rheumatic and musculoskeletal diseases (iRMD), of 694 adults, 438 (63%) developed mild (not hospitalized), 169 (24%) moderate (hospitalized non-ICU) and 87 (13%) severe (ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age, male gender, hypertension and higher BMI. Use of corticosteroids (OR = 1,97), mycophenolate mofetil (OR = 6,6) and rituximab (OR = 4,21) were also risk factors.
References
Bousquet J, Akdis C, Jutel M, et al. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement. Allergy. 2020 Mar 31. PubMed: https://pubmed.gov/32233040. Full-text: https://doi.org/10.1111/all.14302
Brenner EJ, Ungaro RC, Gearry RB, et al. Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology. 2020 Aug;159(2):481-491.e3. PubMed: https://pubmed.gov/32425234. Full-text: https://doi.org/10.1053/j.gastro.2020.05.032
Conforti C, Giuffrida R, Dianzani C, Di Meo N, Zalaudek I. COVID-19 and psoriasis: Is it time to limit treatment with immunosuppressants? A call for action. Dermatol Ther. 2020 Jul;33(4):e13298. PubMed: https://pubmed.gov/32157783. Full-text: https://doi.org/10.1111/dth.13298
FAI2R / SFR / SNFMI / SOFREMIP / CRI / IMIDIATE consortium and contributors. Severity of COVID-19 and survival in patients with rheumatic and in-flammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. Ann Rheum Dis. 2020 Dec 2:annrheumdis-2020-218310. PubMed: https://pubmed.gov/33268442. Full-text: https://doi.org/10.1136/annrheumdis-2020-218310
Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmun Rev. 2020 Mar 20:102523. PubMed: https://pubmed.gov/32205186. Fulltext: https://doi.org/10.1016/j.autrev.2020.102523
Figueroa-Parra G, Aguirre-Garcia GM, Gamboa-Alonso CM, Camacho-Ortiz A, Galarza-Delgado DA. Are my patients with rheumatic diseases at higher risk of COVID-19? Ann Rheum Dis. 2020 Mar 22. PubMed: https://pubmed.gov/32205336. Fulltext: https://doi.org/10.1136/annrheumdis-2020-217322
Gao Y, Chen Y, Liu M, Shi S, Tian J. Impacts of immunosuppression and immunodeficiency on COVID-19: a systematic review and meta-analysis. J Infect. 2020 May 14:S0163-4453(20)30294-2. PubMed: https://pubmed.gov/32417309. Full-text: https://doi.org/10.1016/j.jinf.2020.05.017
Gianfrancesco M, Hyrich KL, Al-Adely S, 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 May 29. PubMed: https://pubmed.gov/32471903. Full-text: https://doi.org/10.1136/annrheumdis-2020-217871
Haberman R, Axelrad J, Chen A, et al. Covid-19 in Immune-Mediated Inflammatory Diseases – Case Series from New York. N Engl J Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348641. Full-text: https://doi.org/10.1056/NEJMc2009567
Kennedy NA, Jones GR, Lamb CA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020 Apr 17. PubMed: https://pubmed.gov/32303607. Full-text: https://doi.org/10.1136/gutjnl-2020-321244
Pasha SB, Fatima H, Ghouri YA. Management of Inflammatory Bowel Diseases in the Wake of COVID-19 Pandemic. J Gastroenterol Hepatol. 2020 Apr 4. PubMed: https://pubmed.gov/32246874. Full-text: https://doi.org/10.1111/jgh.15056
Torres T, Puig L. Managing Cutaneous Immune-Mediated Diseases During the COVID-19 Pandemic. Am J Clin Dermatol. 2020 Apr 10. pii: 10.1007/s40257-020-00514-2. PubMed: https://pubmed.gov/32277351. Full-text: https://doi.org/10.1007/s40257-020-00514-2.