The ongoing COVID-19 pandemic caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often results in a severe acute respiratory syndrome, accompanied by symptoms and signs of fever, cough, interstitial pneumonia, rapid and worsening respiratory difficulty, and sometimes multi-organ dysfunction leading to death.
Arthralgia in Viral Infections
About 15% of patients with COVID-19 present with arthralgia at some point, but not much is known about the nature or presentation of such rheumatic manifestations of this infection. However, it is well-known that viral infections are associated with acute joint inflammation and pain, including single joint involvement with viruses such as the hepatitis B virus, hepatitis C virus, parvovirus, Epstein-Barr virus, and HIV.
Chikungunya and Zika viruses are also commonly associated with post-viral arthralgia. In fact, about one percent of all cases of acute inflammatory arthritis have a preceding viral infection history. As a result, even though challenging to trace, such a history should be sought in all such patients with inflammation of multiple joints and of sudden onset.
Especially in women and older patients, rheumatoid arthritis is present at a higher prevalence in association with circulating viral respiratory infections. This suggests that these infections present an environmental risk factor for this condition.
Inflammatory Signaling in COVID-19
It is now understood that the SARS-CoV-2 virus binds to the host cell receptor, the angiotensin-converting enzyme-2 (ACE-2), to gain entry to and infect the host cell. The virus is then detected by Toll-like receptor-7 (TLR7) via several fragments of the viral genome.
TLR7 is found not only within immunological cells but very strongly in the lung and bronchial tissue. This leads to early recognition of the virus in the very tissue that is most susceptible to it and which harbors the initial infection. The result is the activation of other cellular signaling pathways such as c-Jun N-terminal kinase and NF- κB signaling. This, in turn, leads to the secretion of cytokines such as the pro-inflammatory IL-6 and IL-12p40.
Testing for Viral Arthritis in COVID-19
This scenario makes it plausible that COVID-19 patients might have features of systemic inflammation, including viral arthritis. The current study is aimed at assessing the role of this virus in the etiology of inflammatory arthritis.
One possibility in the confirmation of this diagnosis is serologic testing. However, in viral arthritis, cross-reactive autoantibodies such as the rheumatoid factor (RF) or antinuclear antibody (ANA) which are involved in the pathogenesis, could yield a low-titer false-positive test for COVID-19.
Thus, in addition to serological testing, the epidemiology of the disease, along with the clinical characteristics, must be analyzed to arrive at such a diagnosis. Some of the determining features of viral arthritis include arthritis of more than one joint, either symmetric or asymmetric, which responds well to non-steroidal anti-inflammatory drugs (NSAIDs); early onset of arthritis within the first weeks of COVID-19 symptom onset; and the self-limited nature of the illness.
COVID-19-Associated Arthritis in a White Woman
The current paper published in the The Lancet Rheumatology discusses arthritis in a 58-year-old white woman with COVID-19 of less than severe intensity. She was treated with paracetamol. The first test for COVID-19 was at 25 days from the onset of infection when she reported joint pain, fever, cough, and nausea, along with disturbances of taste and diarrhea. She had a nasal swab taken for testing by reverse transcriptase-polymerase chain reaction (RT PCR).
The patient then had inflammation of an ankle joint, and further laboratory tests showed a small rise in the inflammatory marker CRP, a drop in the lymphocyte count to near the lower limit of normal, and normal liver and kidney function.
The woman was tested for numerous autoantibodies, including ANA, anti-extractable nuclear antigen, anti-ds-DNA, RF, and anti-CCP antibodies, all of which were negative. HLA-B27 was perfrmed to rule out other genetic predispositions to inflammation of the joints and spinal column.
An ultrasound examination showed thickening of the synovial membrane of the ankle, with inflammation of the Achilles tendon. Other tendons were not obviously inflamed. The patient was then treated with the NSAID ibuprofen. This produced significant alleviation of pain and inflammation.
At 30 days from the first symptom, the nasal swab was negative for SARS-CoV-2, as was a second swab at 7 days from the first. By this time, her symptoms had resolved. However, even though the joint pain went down, the ultrasound repeat examination continued to show evidence of inflammation, specifically synovitis. The patient was still in follow up for joint surveillance.
Importance of the Study
The researchers say that though similar cases have been reported in China and one in Thailand, “this is the first case of arthritis in a COVID-19 patient in Europe.” This serves to highlight the importance of looking for this diagnosis when faced with rapid-onset arthritis in the current pandemic scenario.