The novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), responsible for the coronavirus disease 2019 (COVID-19)) outbreak is a major public health concern worldwide, while it is spreading globally.
It is not yet known whether immunomodulatory treatments used in patients with autoimmune and rheumatic diseases are associated with better or poorer outcomes over the course of COVID-19.
We report the case of a recovery from COVID-19 in a 60-year-old immunocompromised man, treated with tumour necrosis factor-alpha (TNF-α) inhibitor (the soluble TNF receptor: etanercept 50 mg, subcutaneous, weekly) and methotrexate (20 mg subcutaneous, weekly), for spondyloarthritis.
One week after the categorisation of eastern France as a new cluster of COVID-19 and 2 days after the weekly subcutaneous injection of 50 mg etanercept, the patient developed fever (up to 39°C), cough, myalgias and diarrhoeas. Five days after the onset of symptoms, the patient was referred to the local emergency department where the SARS-CoV2 was detected by real-time reverse transcription (RT)-PCR on a nasopharyngeal swab. There was no sign of respiratory distress and the patient did not require intensive care unit. Blood tests did not show leucopenia or lymphopenia with 4.12 x 109/L leucocytes and 1.04 x 109/L lymphocytes, respectively. C-reactive protein (CRP) level was 63 mg/L; procalcitonin was 0.06 µg/L. The chest X-ray did not show alveolar or interstitial opacity. Thoracic CT scan was not performed. The treatment consisted of intravenous paracetamol without the need of antiviral drugs, steroids, antibiotics or intravenous immunoglobulins. In addition, no respiratory support was needed over the whole hospitalisation period. The outcome was favourable with regression of fever, cough and myalgias at day 10, along with a decrease of the CRP reaching 16 mg/L. At this stage of the epidemic and given the limited resources for RT-PCR testing, systematic viral monitoring was not performed. The patient was discharged at day 14.
In our observation, the use of a TNF-α inhibitor prior to the viral infection was not associated with a severe evolution of the COVID-19.
To date, there is no effective treatment available for COVID-19. Aside from an antiviral treatment strategy, targeting the inflammatory cascade should be considered, particularly for the most severe cases, in which the development of acute respiratory distress syndrome is intimately associated with a cytokine release syndrome (CRS).
In 2004, E. Tobinick has suggested the use of TNF-α inhibitors for SARS coronavirus infection.1 Although TNF-α inhibitors have failed to demonstrate efficacy for the treatment of septic shock,2 it is unclear whether a cytokine blockade strategy could be effective in CRS associated with COVID-19.3 4
On 17 April 2020, a total of 40 clinical trials out of the 662 registered for COVID-19 (ClinicalTrials.gov) have included biological disease-modifying antirheumatic drugs (b-DMARDs) or targeted synthetic DMARDs (ts-DMARDs), derived from the rheumatological armamentarium,5 to be repurposed for the management of COVID-19-related CRS. Of biologics, priority has so far been given to the interleukin (IL)-6 receptor inhibitors (tocilizumab; sarilumab) and the IL-1 receptor antagonist (anakinra), which are currently evaluated in 21, 8 and 5 trials, respectively. Tocilizumab, sarilumab and anakinra are all included in the French adaptive trial ‘CORIMUNO-19’, a cohort multiple randomised controlled trial (cmRCT) (NCT04331808, NCT04324073 and NCT04341584, respectively). Interestingly, adalimumab is the only TNF-α inhibitor undergoing evaluation, in a trial registered in China (ChiCTR2000030089). Concerning ts-DMARDs, Janus kinase inhibitors tofacitinib and baricitinib are evaluated in one and five trials, respectively.
As the outbreak is spreading exponentially, patients exposed to DMARDs and infected by the SARS-CoV2 will expand concurrently. The implementation, in a collaborative effort of registries dedicated to the report and monitoring of COVID-19 occurring in patients with rheumatic diseases, including the ‘EULAR-COVID-19 database’, ‘The COVID-19 Global Rheumatology Alliance’ registry,6 along with databases supported by national societies, will provide merged data and novel evidence regarding the impact of DMARDs on COVID-19 outcomes.
Acknowledgments
The authors thank the patient for providing consent to report on his case.
Footnotes
Handling editor: Josef S Smolen
Contributors: All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. PMD and ES wrote the manuscript. PMD, SG, AM, LS and LM revised it critically and PMD, LS and LM supervised the project.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
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: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
- 1. Tobinick E. TNF-α inhibition for potential therapeutic modulation of SARS coronavirus infection. Curr Med Res Opin 2004;20:39–40. 10.1185/030079903125002757 [DOI] [PubMed] [Google Scholar]
- 2. Fisher CJ, Agosti JM, Opal SM, et al. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 1996;334:1697–702. 10.1056/NEJM199606273342603 [DOI] [PubMed] [Google Scholar]
- 3. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–4. 10.1016/S0140-6736(20)30628-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Feldmann M, Maini RN, Woody JN, et al. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet 2020. doi: 10.1016/S0140-6736(20)30858-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Favalli EG, Ingegnoli F, De Lucia O, et al. COVID-19 infection and rheumatoid arthritis: Faraway so close! Autoimmun Rev 2020;102523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Robinson PC, Yazdany J. The COVID-19 global rheumatology alliance: collecting data in a pandemic. Nat Rev Rheumatol;39 10.1038/s41584-020-0418-0 [DOI] [PMC free article] [PubMed] [Google Scholar]