Joint symptoms have been seen in a number of patients with COVID-19 infection during the recent pandemic event. These joint involvements can have different etiologies and occur in different joints. For example, drugs used to treat COVID-19 infectious disease such as CS can have side effects on the hip joints and several cases of femoral head AVN following treatment of COVID-19 disease have been reported in individuals treated with CS. Agarwala and colleagues reported three cases of AVN of femoral head following recovery from COVID-19 disease in May 2021; all of them were treated conservatively and their joint symptoms improved significantly(1). These reports indicate the onset of AVN of femoral head in COVID-19 patients was associated with lower doses and shorter duration of CS administration compared to other patients with avascular necrosis of femoral head who did not have COVID-19 disease(11, 12). In addition, endothelial markers were found to have elevated in the blood of critically ill patients with covid-19(13). The autopsy of many of these patients confirmed endothelial dysfunction(14). This endothelial destruction can trigger the pro-inflammatory and pro-coagulant pathways(15) and can lead to generalized microcirculatory dysfunction and related microthrombi (14) Which could potentially be one of the causes of femoral head avascular necrosis in patients with covid-19 infection.
Reactive arthritis is another form of joint complication after different caused by different type of infections, which can be related to mucosal infections in different areas of body such as urogenital (chlamydia) and gastrointestinal (campylobacter, salmonella, shigella, clostridium difficiale, Yersinia) and respiratory pathogens (chlamydia pneumonia)(2, 16, 17). It’s incidence is reported to be 1-1.5% in gastrointestinal infections and 4–8% after urogenital tract infections(16). People with HLA-B27 allele or family history of spondyloarthropaties are more at risk of developing reactive arthritis(16). Most cases of this kind of arthritis are seen in the lower extremities and this is considered as a diagnostic major criteria for the diagnosis of reactive arthritis(17). The prognosis is favorable in most cases and spontaneous improvement is seen in most cases within 6–12 months(16). Cases of reactive arthritis associated with COVID-19 disease have been reported in lower limbs such as knees, ankle, metatarsophalangeal and interphalangeal joints, recently(2, 7, 9, 10). A case of reactive arthritis following COVID-19 disease in the wrist and shoulder has also been reported(2).
Another cause of joint inflammation is viral arthritis which sometimes difficult to detect. It is considered in patients with acute onset poly-articular symptoms. A wide range of viral infections such as parvovirus-B19, hepatitis B, HCV, HIV, alphaviruses, HTLV-1, arboviruses, flaviviruses can cause arthritis(18). It is specially considered in patients who have a history of traveling to certain areas.
Reactive arthritis in different from viral related arthritis, however in the cases of COVID-19 infection recognizing these differences and naming them requires further studies. It should be noted that bacterial infections of body organs, immunological and genetic factors including HLA-B27 play an essential role in the development of reactive arthritis(19). Accurate viral diagnostic tests as well as low-titers autoantibodies such as rheumatoid factor and antinuclear antibody can help differentiate viral arthritis from a reactive one(18). However, both treatments are supportive and anti-inflammatory medications should be considered as treatment.
However, the most destructive type of arthritis is infectious arthritis, the early diagnosis of which, is very important. Joint function is irreversibly lost in 25–50% of cases of infectious arthritis(20). Despite advances in antibiotics and surgical procedures the case fatality rate of septic arthritis in the past 25 years has not changed, ranging from 5–15%(21, 22). The incidence of SA varies from two to ten per 100000 population to 30–70 per 100000 people with rheumatoid arthritis or prosthetic implants(21).
Bacteria that most often cause SA include: staphylococcus aureus, all types of streptococci, all gram negative bacilli, nisseria gonorrhea and anaerobes(21, 22) and the most common risk factor underlying that are: rheumatoid arthritis or osteoarthritis, joint prosthesis, low socioeconomic status, intravenous drug abuse, alcoholism, diabetes, previous intra-articular CS injection and cutaneous ulcers(22).
Diagnosis of SA is based on physical examination of the patient as well as laboratory markers and radiological evidences. Joint fluid aspiration is helpful in 50–67% of cases(23). Fever, redness, swollen and very painful joint movement are common symptoms and raised WBC and erythrocyte sedimentation(ESR) and C-reactive protein(CRP) in peripheral blood are other diagnostic factors, but these tests are very non-specific. Radiological evidences including joint effusion and adjacent lymphadenopathy as well as juxta-articular osteoporosis and bone erosions and osteomyelitis is helpful in prolonged cases. Finally, destruction of articular cartilage on X-rays and MRI is evidence of prolonged joint infection(21–23). Differential diagnoses of SA include gout and pseudo-gout, reactive arthritis, rheumatoid arthritis, lyme disease and viral arthritis, which can be greatly differentiated by accurate history and complete examination as well as various laboratory tests(21).
The most appropriate treatment for septic arthritis is joint drainage and administration of appropriate antibiotics based on the culture results and anti-biogram(21, 22). Complete removal of necrotic and infectious material is mandatory. Joint drainage methods include closed drainage, arthroscopic drainage and open drainage specially in hip joints(22). Appropriateness and adequacy of antibiotic type and dose and duration is determined in the literature and it should cover the most common pathogens (staphylococcus aereus and streptococcus). In patients with the history of recent inpatient, intensive care unit and other risk factors for MRSA, antibiotic regimen should consists of vancomycin with or without second or third generation cephalosporin and in patient with high risk of gram-negative sepsis (elderly, UTI, catheters) it must include second and third generation cephalosporin with or without fluoroquinolones(21, 22). Consultation with infectious disease specialist is strongly recommended.
According to our knowledge, in this study the first cases of septic arthritis in the field of COVID-19 infection and its treatment are reported and given the current pandemic we expect more in the future.
In any patient with the history of COVID-19 infection specially those who have been treated with corticosteroid as one of the medications prescribed during the disease, any joint symptom specially in the hips should draw our attention to the joint infection and take the necessary measures in this regard.