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Large cohort studies demonstrated that a sizeable proportion of patients with acute COVID-19 present with symptoms or signs of rheumatological interest such as arthralgia/myalgia, inflammatory skin lesions and/or autoantibodies positivity.1 Subsequent clinical observations disclosed the existence of a post-acute COVID-19 syndrome, characterised by a large constellation of manifestations including fatigue, arthralgia and myalgia.2 The potential role of viruses in the development of rheumatic diseases is well recognised, either as causative agents or antigenic triggers for the ensuing development of autoimmunity.3 Consistent with these premises, from the earliest phases of the pandemic, inflammatory musculoskeletal manifestations following COVID-19 have been described in isolated case reports although no systematically collected cohorts are still available to unveil the clinical spectrum of post-COVID-19 arthritis.4
To contribute to shed light on this field, in December 2020, we built a web-based survey platform and invited all members of our study group to submit cases of inflammatory joint disease and onset within 8 weeks from a confirmed SARS-CoV-2 infection (demonstrated either by reverse transcription PCR on nasopharyngeal swab or SARS-CoV-2-specific IgM antibodies) encountered during routine clinical practice from 31 January 2020 and up to 31 March 2021. Exclusion criteria were a history of any inflammatory rheumatic disease or psoriasis. General characteristics of the patients are reported in table 1.
The clinical spectrum of rheumatic manifestations spanned from asymmetric monoarthritis or oligoarthritis (51%) to rheumatoid arthritis (RA)-like symmetric polyarthritis of the small joints (20%). Furthermore, 11% of cases presented with predominantly axial involvement (inflammatory back pain and evidence of sacroiliitis/spondylitis on MRI) and polymyalgia rheumatica-like involvement of shoulder and hip girdles, respectively. Finally, two patients had isolated peripheral enthesitis. Autoantibodies were usually absent, except for non-specific antinuclear antibody positivity encountered in 22% of cases. The overall course was relatively benign with half of the patients experiencing remission of the symptoms after treatment with non-steroidal anti-inflammatory drugs, glucocorticoids or disease-modifying antirheumatic drugs. Further, we stratified patients according to the delay between COVID-19 and arthritis onset as early (≤2 weeks) or late (>2 weeks), on the basis of the approximated average duration of COVID-19 symptoms in the outpatient setting. Strikingly, we observed a clustering of RA-like pattern in patients with early arthritis onset; the only two cases of oligoarthritis in this subset affected small joints of hands and wrist; furthermore, two out of three patients with axial involvement had also pain in metacarpophalangeal and proximal interphalangeal joints.
We hypothesise that such a clustering may suggest different underlying pathophysiological mechanisms. On the one hand, the earlier RA-like pattern is similar to what observed in other virus-associated arthritis, such as parvovirus B19 or hepatitis C virus-related arthritis.5 On the other hand, the monoarticular or oligoarticular forms resemble the clinical features of reactive arthritis. For this reason, we speculate that the arthritogenic potential of SARS-CoV-2 may be broad and exploit both direct viral and indirect dysimmune mechanisms. Unfortunately, our report is affected by the intrinsic limitations of a real-life case series. Synovial fluid analysis was not carried out and thus it is not possible to exclude acute illness-triggered crystal arthritis6 although not having performed joint aspiration implies that the clinical probability was considered low according to rheumatologist’s clinical judgement. Moreover, no attempt to isolate SARS-CoV-2 RNA in synovial samples was made. In conclusion, despite our data do not allow to draw firm conclusions regarding the causative role of SARS-CoV-2 in the development of arthritis, they represent a fascinating hypothesis-generating basis for further systematic studies aimed at elucidating mechanisms behind this new entity.
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Handling editor Josef S Smolen
Contributors FU and CF conceived the work and drafted the manuscript. All authors contributed to the acquisition and interpretation of data and to the critical revision of the draft. All authors approve the final version of the manuscript and agree to be accountable for all aspects of the work.
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.
Provenance and peer review Not commissioned; externally peer reviewed.