Project description:To construct a model of the antibody response to COVID-19 vaccination in patients with rheumatoid arthritis (RA), and to identify clinical factors affecting the antibody response. A total of 779 serum samples were obtained from 550 COVID-19-naïve RA patients who were vaccinated against COVID-19. Antibody titers for the receptor binding domain (anti-RBD) and nucleocapsid (anti-N) were measured. The time from vaccination, and the log-transformed anti-RBD titer, were modeled using a fractional polynomial method. Clinical factors affecting antibody responses were analyzed by a regression model using generalized estimating equation. The anti-RBD titer peaked at about 2 weeks post-vaccination and decreased exponentially to 36.5% of the peak value after 2 months. Compared with the first vaccination, the 3rd or 4th vaccinations shifted the peaks of anti-RBD antibody response curves significantly upward (by 28-fold [4-195] and 32-fold [4-234], respectively). However, there was no significant shift in the peak from the 3rd vaccination to the 4th vaccination (p = 0.64). Multivariable analysis showed that sulfasalazine increased the vaccine response (by 1.49-fold [1.13-1.97]), but abatacept or JAK inhibitor decreased the vaccine response (by 0.13-fold [0.04-0.43] and 0.44-fold [0.26-0.74], respectively). Age was associated with lower ln [anti-RBD] values (coefficient: - 0.03 [- 0.04 to - 0.02]). In conclusion, the anti-RBD response of RA patients peaked at 2 weeks after COVID-19 vaccination, and then decreased exponentially, with the maximum peak increase observed after the 3rd vaccination. The antibody response was affected by age and the medications used to treat RA.
Project description:Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including RA, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated autoinflammatory diseases, graft-versus-host disease, diabetic kidney disease, and, recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients, ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib, versus the probable adverse effects, urge further investigation before establishing it as a part of standard therapeutic protocols. Here, we have provided a review of the studies that have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.
Project description:Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.
Project description:BackgroundTo evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles.MethodsTwelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2.ResultsNine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose "normal" expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women.ConclusionsThe large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.
Project description:Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.
Project description:In March 2020, COVID-19 infection caused by SARS-CoV-2 has been declared to be a global pandemic, where its complications, severity and mortality are reported to be due to the released inflammatory cytokines or the so-called cytokine storm. This is quite similar to that observed in the autoimmune and chronic inflammatory rheumatic disease, rheumatoid arthritis (RA). It was hypothesized that RA patients are at a higher risk of acquiring COVID-19; however, recent studies reported that they are not when compared to the rest of the population. In this review, we aim to highlight the mutual pathological features, cytokine profiles and risk factors between COVID-19 and RA. Also, many researchers are currently working to explore therapeutic agents that could aid in the eradication of COVID-19 infection. Due to the similarity between the inflammation status in COVID-19 and RA, many anti-rheumatic drugs such as hydroxychloroquine, tocilizumab, baricitinib and anakinra were proposed to be therapeutic modalities for COVID-19 infection.
Project description:Introduction and importance:Coronavirus disease 2019 (COVID-19) is a recently discovered disease that has yet to be thoroughly described. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that can be transmitted easily from human to human, mainly by the respiratory route. The disease often presents with non-specific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Currently, vaccination is the primary strategy to prevent transmission and reduce disease severity. However, vaccines have side effects, and the consequences of vaccination in different diseases are not well established. Moreover, the impact of SARS-CoV-2 vaccination during pregnancy is another not well-known area. Case presentation:We present a young lady known to have ITP, which was controlled for years, presented with relapse after taking the SARS-CoV-2 vaccine during pregnancy. Clinical discussion:The patient had a relapse of ITP after the introduction of the first dose of the COVID-19 vaccine, which worsened further after the second dose. This suggests that patients with ITP who develop flare post-SARS-CoV-2 vaccine should have their second dose delayed, particularly if pregnant. Conclusion:To avoid further deterioration in platelet count, and avoid confusion due to the presence of different causes of thrombocytopenia and avoid complications related to thrombocytopenia during pregnancy which can affect the mode of delivery. The case is reported in line with the scare 2020 criteria:Agha RA, Franchi T, Sohrabi C, Mathew G, for the SCARE Group. The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines, International Journal of Surgery 2020; 84:226-230.
Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes prior to COVID-19 mRNA booster vaccination. D01 and D21 correspond to samples collected at pre-dose 1 and pre-dose 2 respectively. RNA was also extracted from blood collected at indicated time points post-vaccination. DB1, DB2, DB4 and DB7 correspond to booster day 1 (pre-booster), booster day 2, booster day 4 and booster day 7 respectively. The case subject experienced cardiac complication following mRNA booster vaccination. We performed gene expression analysis of case versus controls over time.
Project description:Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we used the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes, allowing characterisation with unprecedented detail. We used single cell RNA sequencing to analyse the diversity and comparative longitudinal changes in paired circulating lymphocyte samples from 12 patients with RA in remission prior to drug cessation (on-drug remission) and after drug cessation (either off drug flare, or drug-free remission) as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study.