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 Table of Contents  
BRIEF REPORT
Year : 2022  |  Volume : 17  |  Issue : 2  |  Page : 153-156

Coronavirus Disease-19 associated arthritis – An observational study


Department of Clinical Immunology and Rheumatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India

Date of Submission22-Jun-2021
Date of Acceptance01-Aug-2021
Date of Web Publication21-May-2022

Correspondence Address:
Dr. Sumantro Mondal
Doctor's Quarter, 242 AJC Bose Road, Kolkata - 700 020, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_133_21

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  Abstract 


Background: The coronavirus disease or COVID-19 pandemic is the major global health crisis of the present time. Various rheumatological manifestations have been reported during or after COVID-19 infection, but data are scarce. In this observational study, we have tried to analyze the clinical characteristics of COVID-19 associated arthralgia/arthritis.
Methods: We have collected the clinical data of 14 patients over the past 6 months who have developed arthralgia or arthritis during or after symptomatic COVID-19 infection, proven by a positive reverse transcription-polymerase chain reaction test from nasopharyngeal swab.
Results: The most common symptoms during COVID-19 infection in the 14 patients were fever and myalgia, being present in 92.8% and 64.3% patients, respectively. Arthralgia/arthritis occurred at a mean interval of 20 days (range: 0–60 days). Knee was the most commonly involved joint (78.6%), followed by the wrist and metacarpophalangeal joints (each in 57.1%). Enthesitis was documented in 21.4% patients. The mean duration of COVID-19 associated arthralgia or arthritis was 53.9 days (range: 7–210 days). In 85.7% patients, joint pains improved within 2 months; in only a small proportion of patients (14.3%), joint pains persisted after 6 months. Nonsteroidal anti-inflammatory drugs (NSAIDs) (given in 64.3% patients) and corticosteroids (in 50%) were the most commonly prescribed and effective treatment options.
Conclusion: COVID-19 infections mostly caused reactive arthritis, though acute and chronic arthritis is also seen. In the majority of cases, arthritis started about 3 weeks after COVID-19 infection and subsided within 2 months. NSAIDs and corticosteroids are the most effective treatment options.

Keywords: Arthralgia, arthritis, coronavirus disease-19, reactive arthritis


How to cite this article:
Sinha D, Mondal S, Ghosh A. Coronavirus Disease-19 associated arthritis – An observational study. Indian J Rheumatol 2022;17:153-6

How to cite this URL:
Sinha D, Mondal S, Ghosh A. Coronavirus Disease-19 associated arthritis – An observational study. Indian J Rheumatol [serial online] 2022 [cited 2022 Jul 4];17:153-6. Available from: https://www.indianjrheumatol.com/text.asp?2022/17/2/153/345781




  Introduction Top


Viral infections are responsible for approximately 1 and continue to wreak havoc in the world even after 1 1/2 years of its first appearance. A few case reports described reactive arthritis after COVID-19 infection% of all cases of acute arthritis.[1] The spectrum of symptoms is wide, comprising of arthralgia, acute, and chronic arthritis. Chronic arthritis can be caused by Hepatitis C and several alphaviruses. Self-limited, acute arthritis occurs with parvovirus B19, rubella, or Hepatitis B virus and rarely with herpes, coxsackie, measles, mumps, and rubella viruses. Arthralgia and/or myalgia are usually caused by influenza, dengue, and the coronaviruses.[2] HIV can be associated with a myriad of rheumatological conditions, including arthralgias, reactive arthritis, and psoriatic arthritis.

The coronavirus disease (COVID-19) pandemic is currently the defining global health crisis. One of the first cases was published by Ono et al., in August 2020.[3] Subsequently, similar case reports were published from different countries.[4],[5],[6],[7] Novelli et al. and de Stefano et al. published cases of psoriatic arthritis after COVID-19 infection.[8],[9] In a large data on 1099 COVID-19 patients from China, 14.9% of patients had arthralgias and myalgias.[10] Musculoskeletal symptoms were not associated with COVID-19 severity.[10]

With the expanding numbers of COVID-19 patients, various manifestations are now being reported. The rheumatological manifestations of COVID-19 infection are mostly reported in the form of case reports or small series. Prospective studies in patients with COVID-19 associated rheumatological manifestations would provide valuable information, although lacking.


  Methods Top


This observational study is being conducted at the Department of Clinical Immunology and Rheumatology of IPGME and R, Kolkata. Over the past 6 months, the clinical and laboratory data of 14 patients who attended the outpatient clinic with a history of arthralgia and/or arthritis that developed after COVID-19 infection have been collected. This study was approved by the IPGME and R Research Oversight Committee (Institutional Ethics Committee for Research involving Human Participants). Informed consent was taken from all the patients.

Inclusion criteria

  • Onset of arthritis/arthralgias during or within 3 months of symptomatic COVID-19 infection
  • A positive reverse transcription-polymerase chain reaction test for COVID-19 from the nasopharyngeal swab.


Exclusion criteria

  • Prior history of any inflammatory arthritis/connective tissue disease.



  Results Top


The median age of the patients was 35.5 years. Nine were females (64.3%).

Fever was the most common symptom during COVID-19 infection, occurring in 13 patients (92.8%). The mean duration of fever was 5.5 days. Myalgia was present in nine patients (64.3%), anosmia in eight (57.1%), and sore throat in seven patients (50%). Headache was present in five patients (35.7%), and diarrhea in four patients (28.6%). The lower respiratory tract was involved in six patients (42.8%), and cough was present in all six patients, but respiratory distress in only two. Three patients (21.4%) had a morbilliform rash during the COVID-19 infection that preceded the onset of arthritis/arthralgia by a mean duration of 2.3 days. One patient had associated leukopenia and thrombocytopenia. The severity of COVID-19 symptoms was mild in the majority of patients, 12/14 (85.7%); only two patients had moderate disease (14.3%). Comorbidities in the form of coronary artery disease and hypertension were present in two patients (14.3%) and diabetes, hypothyroidism, and chronic kidney disease in one patient each (7.1%).

The rheumatologic manifestation occurred at a mean interval of 20 days from the first manifestation of COVID-19. The earliest onset of rheumatological symptom/s was on the same day of COVID-19 symptoms and the longest interval was 60 days. Six patients (42.9%, n = 6) had onset of arthralgia/arthritis 1–4 weeks after COVID-19 infection. Five patients (35.7%) had their joint symptoms within 1 week of ongoing COVID-19 infection and 3 (21.4%) had onset after 4 weeks.

Arthritis was present in 9 (64.3%) patients, and arthralgia in the rest (5; [35.7%]). The onset of joint pain was acute in 5 (35.7%) patients and subacute in 9 (64.3%) patients. The musculoskeletal involvement was polyarticular in 7 (50%) patients, oligoarticular in 6 (42.8%), and monoarticular in one patient (7.1%). Early morning stiffness was present in 9 (64.3%) patients. Joint swelling was present in eight patients. The mean tender joint count was 12.2 and the mean swollen joint count 1.6.

Knee joint involvement was the most common, was seen in 11 patients (78.6%), followed by the wrist and metacarpophalangeal joints, each present in 8 different individuals (57.1%). The third most commonly involved joint was the ankle, being present in seven patients (50%). The other joints in decreasing order of the frequency of involvement were as follows: shoulder (6; [42.9%]), elbow (3; [21.4%]), midfoot (3; [21.4%]), and metatarsophalangeal joint (1; [7.1%]). Low back pain was present in two patients (14.3%), with magnetic resonance imaging documented sacroiliitis in one of them. Evidence of enthesitis was found in 3 (21.4%) patients, all involving the tendoachilles. There was a preceding history of diarrhea in one patient and dysuria in another patient, each occurred 2 weeks before the onset of arthritis/arthralgia. The mean intensity of joint pain was 6.2 on a 0–10 visual analog scale. Eye involvement was present in two patients, one in the form of conjunctivitis and the other uveitis.

The mean duration of COVID-19 associated arthralgia/arthritis was 53.9 days (range: 7–210 days). In the majority of the patients (12; [85.7%]), joint pain improved within 2 months. In 2 patients (14.3%), joint pain persisted longer and continued after 6 months.

C-reactive protein was done in ten patients; it was elevated in 8 of them (80%). Rheumatoid factor (RF) was tested in eight patients, out of whom two were positive. Human leukocyte antigen-B27 was done in three patients and positive in one.

Nonsteroidal anti-inflammatory drugs (NSAIDs) were used for the treatment of COVID-19 associated arthralgia/arthritis in nine patients (64.3%), and it was associated with good response. Corticosteroids resulted in good symptomatic improvement in all patients to whom it was offered in any form: intramuscular depot corticosteroid injection was given to four patients, oral steroids to two patients, and an intra-articular corticosteroid to one. Acetaminophen solely was used in three patients and was associated with delayed response.


  Discussion Top


This study is intended to find the spectrum of COVID-19 associated musculoskeletal manifestations which would provide information to deal with similar patients in the future.

Although the exact prevalence of COVID-19 associated arthritis is not known, joint pain does not seem to be very common in patients with COVID-19. In a recent review article by Conway et al. on “Inflammatory arthritis in patients with COVID-19,” it has been pointed out that despite about 44 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection worldwide during the first wave, only 9 discrete cases of acute arthritis have been reported in the literature.[11]

The most common symptom during COVID-19 infection in our cohort was fever and myalgia. Measles-like rash is a less reported manifestation of COVID-19, was present in 21.4% of our patients, and preceded the onset of joint symptoms. Arthritis occurred in about two-third of the patients and arthralgias in the rest. The tender joint count was disproportionately more than the swollen joint count, suggesting that despite significant pain, joint swelling was not common. Enthesitis mostly involving the tendoachilles occurred in 21.4% of the patients of our cohort. Enthesitis has also been found to be a common feature in the other case reports. We did not find any case of psoriatic arthritis in our patients.

Although the majority of the patients had onset of their joint symptoms 1–4 weeks after COVID-19 infection, typically in the period when reactive arthritis occurs, some patients had initiation of joint pains within a week of onset of COVID-19 symptoms and during active ongoing infection. Hence, it is likely that COVID-19 infection not only causes reactive arthritis but also acute arthritis mimicking viral arthritis. There are 2 such case reports of de novo seronegative inflammatory polyarthritis with onset during acute COVID-19 infection.[12],[13] Viral illnesses are less common cause of reactive arthritis, but COVID-19 infection is now gradually emerging as a plausible etiology in triggering reactive arthritis. Non-SARS-COV-2 coronaviruses can cause arthralgias but are not known to cause arthritis; COVID-19 is standing out as an exception among the other coronaviruses in causing significant arthritis.[11]

In the majority of our patients, joint pains improved within 2 months. Chronic arthritis more than 6 months persisted in 14.3% of patients. NSAIDs and corticosteroid were beneficial for patients with COVID-19 associated arthralgias/arthritis.

We found RF positivity in two patients, however, due to the lack of data regarding their pre-COVID-RF status, it is not possible to conclude whether COVID-19 infection resulted this seroconversion or not. One recent Dutch study reported the onset of rheumatoid arthritis like polyarthritis following COVID-19 infection.[14] Another previous study showed the presence of antinuclear antibody, antineutrophil cytoplasmic antibody, anticardiolipin and beta-2-genuine progress indicator, and anticyclic citrullinated peptide antibody in a small proportion of severely ill COVID-19 patients with unclear significance.[15] The exact mechanism of the development of autoimmune rheumatic diseases following COVID-19 infection is still under research. Molecular mimicry and dysregulation of the immune response following this infection are postulated.[16] Importantly, SARS-COV2 RNA has been detected from different body fluids (saliva, tear) but not from synovial fluid.[17] This finding further reinforces the concept of autoimmunity over direct viral invasion as the causative factor of post-COVID arthritis. In our study, synovial fluid was not tested for SARS-COV2 RNA. Gout exacerbations are common after any infections and have been reported following COVID-19 infection.[18] We have thus not recruited patients with a prior history of gout in this study.

This is preliminary data regarding the spectrum of COVID-19 associated rheumatological manifestations and their short-term outcome. Inclusion and study of larger number of patients and following them for a longer period would help us to understand post-COVID musculoskeletal syndromes better.

Ethical standards

This study was approved by the IPGME and R Research Oversight Committee (Institutional Ethics Committee for Research involving Human Participants). Informed consent was taken from all the patients. The study was performed following the 1964 Declaration of Helsinki and its later amendments.


  Conclusion Top


Different types of arthritis can be seen in association with or following COVID-19 infection, reactive arthritis being the most common variety. Knee joint was the most commonly affected joint. Most of the patients responded well with NSAID/corticosteroid treatment within 2 months.

Patient consent

Informed consent was taken from each participant.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Varache S, Narbonne V, Jousse-Joulin S, Guennoc X, Dougados M, Daurès JP, et al. Is routine viral screening useful in patients with recent-onset polyarthritis of a duration of at least 6 weeks? Results from a nationwide longitudinal prospective cohort study. Arthritis Care Res (Hoboken) 2011;63:1565-70.  Back to cited text no. 1
    
2.
Marks M, Marks JL. Viral arthritis. Clin Med (Lond) 2016;16:129-34.  Back to cited text no. 2
    
3.
Ono K, Kishimoto M, Shimasaki T, Uchida H, Kurai D, Deshpande GA, et al. Reactive arthritis after COVID-19 infection. RMD Open 2020;6:e001350.  Back to cited text no. 3
    
4.
Parisi S, Borrelli R, Bianchi S, Fusaro E. Viral arthritis and COVID-19. Lancet Rheumatol 2020;2:e655-e657. [doi: 10.1016/S2665-9913 (20) 30348-9].  Back to cited text no. 4
    
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Saricaoglu EM, Hasanoglu I, Guner R. The first reactive arthritis case associated with COVID-19. J Med Virol 2021;93:192-3.  Back to cited text no. 5
    
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Danssaert Z, Raum G, Hemtasilpa S. Reactive arthritis in a 37-year-old female with SARS-CoV2 infection. Cureus 2020;12:e9698.  Back to cited text no. 6
    
7.
Yokogawa N, Minematsu N, Katano H, Suzuki T. Case of acute arthritis following SARS-CoV-2 infection. Ann Rheum Dis 2020;80: e101. [doi: 10.1136/annrheumdis-2020-218281].  Back to cited text no. 7
    
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Novelli L, Motta F, Ceribelli A, Guidelli GM, Luciano N, Isailovic N, et al. A case of psoriatic arthritis triggered by SARS-CoV-2 infection. Rheumatology (Oxford) 2021;60:e21-3.  Back to cited text no. 8
    
9.
De Stefano L, Rossi S, Montecucco C, Bugatti S. Transient monoarthritis and psoriatic skin lesions following COVID-19. Ann Rheum Dis 2020;218520. [doi: 10.1136/annrheumdis-2020-218520].  Back to cited text no. 9
    
10.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 10
    
11.
Conway R, Konig MF, Graef ER, Webb K, Yazdany J, Kim AHJ. Inflammatory arthritis in patients with COVID-19. Transl Res 2021;232:49-59.  Back to cited text no. 11
    
12.
Talarico R, Stagnaro C, Ferro F, Carli L, Mosca M. Symmetric peripheral polyarthritis developed during SARS-CoV-2 infection. Lancet Rheumatol 2020;2:e518-9.  Back to cited text no. 12
    
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Alivernini S, Cingolani A, Gessi M, Paglionico A, Pasciuto G, Tolusso B, et al. Comparative analysis of synovial inflammation after SARS-CoV-2 infection. Ann Rheum Dis 2020;80:e91. [doi: 10.1136/annrheumdis-2020-218315].  Back to cited text no. 13
    
14.
Derksen VF, Kissel T, Lamers-Karnebeek FB, van der Bijl AE, Venhuizen AC, Huizinga TW, et al. Onset of rheumatoid arthritis after COVID-19: Coincidence or connected? Ann Rheum Dis 2021;80:1096-98. [doi: 10.1136/annrheumdis-2021-219859].  Back to cited text no. 14
    
15.
Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, et al. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis 2020;79:1661-3.  Back to cited text no. 15
    
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Galeotti C, Bayry J. Autoimmune and inflammatory diseases following COVID-19. Nat Rev Rheumatol 2020;16:413-4.  Back to cited text no. 16
    
17.
Tang KT, Hsu BC, Chen DY. Autoimmune and rheumatic manifestations associated with COVID-19 in adults: An updated systematic review. Front Immunol 2021;12:645013.  Back to cited text no. 17
    
18.
López-González MD, Peral-Garrido ML, Calabuig I, Tovar-Sugrañes E, Jovani V, Bernabeu P, et al. Case series of acute arthritis during COVID-19 admission. Ann Rheum Dis 2020;80:e58. [doi: 10.1136/annrheumdis-2020-217914].  Back to cited text no. 18
    




 

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