New-Onset Arthritis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its symptoms, but there are also many adverse events. Joint diseases caused by COVID-19 vaccine have been reported in many studies. Some are well-controlled arthritis patients who developed arthritis after COVID-19 vaccination, while others are new-onset joint pain and swelling problems after COVID-19 vaccination. The purpose of this systematic review is to examine the literature reports in existing databases and analyze the incidence of new-onset arthritis after COVID-19 vaccination. We included 31 eligible articles and described 45 patients, ranging in age from 17 to over 90, with more females than males. The majority (84.4%) of patients received the adenovirus vector vaccine (ChAdOx1) and the mRNA-based vaccine (BNT126b2 and mRNA-1273). Most (64.4%) patients developed joint-related symptoms after the first dose of vaccine, and 66.7% developed symptoms within the first week of vaccination. The joint symptoms involved were mainly joint swelling, joint pain, limited range of motion, and so on. A total of 71.1% of the patients involved multiple joints, both large and small; 28.9% of patients involved only a single joint. Some (33.3%) patients were confirmed by imaging, and the most common diagnoses were bursitis and synovitis. Two nonspecific inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were monitored in almost all cases, and all patients showed varying degrees of increase in these two markers. Most of the patients received the treatment of glucocorticoid drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical symptoms markedly improved in most patients, with 26.7% making a full recovery and no relapse after a few months of follow-up. To determine whether there is a causal relationship between COVID-19 vaccination and the triggering of arthritis, large-scale and well-controlled research studies are needed in the future to verify this relationship and to further study its pathogenesis in detail. Clinicians should raise awareness of this complication with a view to early diagnosis and appropriate treatment.

SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. METHODS: This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. RESULTS: The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. CONCLUSIONS: The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstract.

Effects of Biologic Therapies on the Chance of COVID-19 Infection Among Rheumatoid Arthritis and Lupus Patients During the First Wave of the Pandemic.

Background: Patients with rheumatic diseases taking immunosuppressive medications might be at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the effectiveness of using combined conventional and biological disease-modifying anti-rheumatic drugs(bDMARDs) in managing rheumatic diseases, there have been concerns that taking biological agents may have an additive effect on getting infected with COVID-19. This study evaluates the impact of taking biological agents on altering the chance of getting infected with SARS-CoV-2 in rheumatoid and lupus patients compared to traditional DMARDs. Methods: We carried out a cross-sectional survey study from February 2020 to January 2021 on patients diagnosed with lupus and rheumatoid arthritis disease. COVID-19 infection was confirmed by the presence of symptoms and signs of the disease and para-clinical findings such as lymphopenia and elevated C-reactive protein (CRP) and positive chest CT scan or polymerase chain reaction (PCR) of COVID-19. Results: Out of 591 patients included in this study, 422 (71.4%) had rheumatoid arthritis (RA), and 169 (28.6%) had systemic lupus erythematosus (SLE). Among them, 56 (9.5%) cases were diagnosed with COVID-19 infection. No association was found between age, gender, or type of rheumatological diseases and SARS-CoV-2. There was a significant association between COVID-19 infection and treatment with biological drugs (P-value<0.05) regardless of the type of rheumatologic disease. Interestingly, the analysis revealed that the type of biologic drug also altered the chance of COVID-19 infection; In fact, patients who took TNF inhibitors were significantly at a higher risk of disease than those taking Rituximab (P-value=0.000). Identical results were observed among RA patients (P-value<0.001), however, all 5 (3%) lupus cases treated with Rituximab infected with covid 19. Conclusion: This study develops a better understanding of the risk of immunosuppressive medications for SARS-CoV-2 infection. Patients treated with conventional and biological medicine had a higher disease risk than those taking exclusively conventional drugs. However, more studies are required to deliberate the relation of the reviewed factors with the severity of COVID-19.

Network pharmacology and bioinformatics analysis identified essential genes of Jingulian in the treatment of rheumatoid arthritis and COVID-19.

Background: Patients with rheumatoid arthritis (RA) may be more susceptible to infection by coronavirus disease-19 (COVID-19) due to immune system dysfunction. However, there are still insufficient treatment strategies for patients with RA and COVID-19. Since Jingulian is a traditional Chinese medicine (TCM) with anti-viral and immune regulatory functions, our study aims to explore the detailed mechanisms of Jingulian in treating patients with RA and COVID-19. Methods: All the components of Jingulian were retrieved from pharmacology databases. Then, a series of network pharmacology-based analyses and molecular docking were used to understand the molecular functions, core targets, related pathways, and potential therapeutic targets of Jingulian in patients with RA/COVID-19. Results: A total of 93 genes were identified according to the disease-compound-target network. We investigated that the main targets, signaling pathways, and biological functions of Jingulian in RA and COVID-19. Our results indicated that Jingulian may treat patients with RA/COVID-19 through immune processes and viral processes. Moreover, the results of molecular docking revealed that tormentic acid was one of the top compounds of Jingulian, which had high affinity with Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR) in patients with RA/COVID-19. Furthermore, 5 core targets of Jingulian were also identified, including JAK1, Janus kinase 2 (JAK2), STAT3, lymphocyte specific protein tyrosine kinase (LCK), and EGFR. Conclusions: Tormentic acid in Jingulian may regulate JAK1, STAT3, and EGFR, and might play a critical role in RA/COVID-19.

The Effects of Vitamin D on Immune System and Inflammatory Diseases.

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.