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Broad clinical spectrum of SARS-CoV-2-associated inflammatory joint disease in adults: a report of 35 cases from the COVID-19 & Autoimmune Systemic Disease Italian study group
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  1. Francesco Ursini1,2,
  2. Piero Ruscitti3,
  3. Salvatore D'Angelo4,
  4. Fabio Cacciapaglia5,
  5. Rossella De Angelis6,
  6. Corrado Campochiaro7,
  7. Francesco Caso8,
  8. Maria De Santis9,
  9. Ilenia Di Cola3,
  10. Simone Parisi10,
  11. Vincenzo Raimondo11,
  12. Giuseppina Abignano4,
  13. Luisa Costa8,
  14. Jacopo Ciaffi1,
  15. Lorenzo Dagna7,
  16. Annamaria Iagnocco12,
  17. Florenzo Iannone13,
  18. Riccardo Meliconi1,2,
  19. Roberto Giacomelli14,
  20. Clodoveo Ferri11,15
  1. 1 Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
  2. 2 Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy
  3. 3 Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila Faculty of Medicine and Surgery, L'Aquila, Italy
  4. 4 Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, Regional Hospital San Carlo, Potenza, Italy
  5. 5 Rheumatology Unit, Department of Emergence Medicine and Transplantation (DETO), Università degli Studi di Bari Facoltà di Medicina e Chirurgia, Bari, Italy
  6. 6 Rheumatology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche School of Medicine and Surgery, Ancona, Italy
  7. 7 Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele, Milano, Italy
  8. 8 Rheumatology Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli, Italy
  9. 9 Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
  10. 10 Rheumatology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
  11. 11 Rheumatology Unit, Rheumatology Hospital "Madonna dello Scoglio", Cotronei, Italy
  12. 12 Academic Rheumatology Centre, Università degli Studi di Torino, Torino, Italy
  13. 13 Rheumatology Unit, Department of Emergency Medicine and Transplantation, Università degli Studi di Bari Aldo Moro, Bari, Italy
  14. 14 Rheumatology and Immunology Unit, Department of Medicine, Campus Bio-Medico University, Roma, Italy
  15. 15 Rheumatology Unit, School of Medicine, Università degli Studi di Modena e Reggio Emilia Facoltà di Medicina e Chirurgia, Modena, Italy
  1. Correspondence to Professor Clodoveo Ferri, Rheumatology Clinic 'Madonna dello Scoglio', Cotronei, Italy; clferri{at}unimore.it

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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.

Table 1

Clinical features and laboratory/imaging findings in patients with SARS-CoV-2-associated inflammatory joint disease

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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Footnotes

  • 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.

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