To assess the impact of severe COVID-19 in patients with immune-mediated rheumatic diseases (im-RD) and compare their morbidity, mortality, hospitalization issues, post-COVID-19 sequelae, and the financial burden of COVID-19 with those of patients without im-RD.

We conducted a retrospective case-control study that included 132 consecutive patients with im-RD who visited the Rheumatology Department of a public hospital in the Emirate of Dubai and were hospitalized for COVID-19 infection between March 1st, 2020, and December 31st, 2021, (cases). We included 264 and 132 age- and sex-matched patients without im-RD in matched-I and matched-II control groups, respectively. The median age of patients and controls was 48.5 years, and 74.2% were female. Patients with im-RD were paired with an unforced nearest neighbor match using a caliper width of 0.2 standard deviations of the matched-II control group's propensity score. We compared the relative risk of death, disease progress, use of medical resources, and financial impact of COVID-19 between patients and controls.

Patients with im-RD had higher mortality rates than the matched-I (odds ratio, OR: 11.2, p < 0.000) and matched-II (OR: 16.8, p < 0.006) control groups. The overall complication rate was also significantly higher in patients with im-RD than in matched-I (OR = 2.9, p < 0.000) and matched-II (OR = 2.8, P < 0.0001) control groups. Lastly, patients with im-RD required more frequent visits to the clinic, a longer recovery time following hospital discharge, and increased healthcare costs compared to the control groups.

COVID-19 infection in patients with im-RD is associated with increased morbidity and mortality, exerting a significant burden on the healthcare system.

Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have a high risk of serious infection, in particular severe pneumonia. This study aimed to investigate the transcriptional landscape, lower respiratory tract (LRT) microbiome and metabolomic profiles in the lung of RA-ILD patients with pneumonia.

A total of 10 RA-ILD with pneumonia were enrolled in this study. In addition, 11 patients with COVID-19-associated pneumonia and 6 patients with non-autoimmune and non-COVID-19-related ILD with pneumonia were included as controls. Bronchoalveolar lavage fluid (BALF) was collected and prepared for metagenomic next-generation sequencing (mNGS), non-targeted metabolomics and bulk RNA-seq.

Neutrophil-related genes were shared in the BALF cells of RA-ILD patients with pneumonia and patients with COVID-19-associated pneumonia. Carnobacterium, Wujia, Intestinimonas, Apibacter, Anaerotignum and Parvimonas were enriched in the LRT microbiome of RA-ILD, while Wujia, Apibacter, Pseudocitrobacter, and Thermobacillus were enriched in the LRT microbiome of COVID-19. Metabolomics analysis of BALF revealed significant elevation of indoxyl sulfate (IS) in the BALF of RA-ILD patients in comparison to COVID-19. Mechanistically, IS exerts an pro-inflammatory effect on macrophages and bronchial epithelial cells for pro-inflammatory cytokine production and potentiated neutrophils for neutrophil extracellular traps (NETs) formation.

Our results demonstrated a significant differences in the LRT microbiome and BALF metabolites between RA-ILD and COVID-19 patients with pneumonia, although they displayed similar local immune responses against lung infection. Alterations of LRT microbiome and related metabolites may be implicated in the pathogenesis of pneumonia in RA-ILD.

Autoimmune rheumatic diseases (AIRDs) are diseases with complex outset and courses, in which both genetic and environmental factors participate. Many environmental factors can be committed to AIRDs outset and development. The most popular of them, with confirmed impact, are smoking, age, gender, and microorganisms. In light of recent research an assumption about the importance of various microorganisms in the pathogenesis of AIRDs is growing in popularity. The human immune system has various protective mechanisms against infectious antigens which in normal cases let organism manage potential infection faster and more effectively. Unfortunately in some situations, specific errors in those mechanisms can cause an autoreactive response despite mitigation of infection. Viruses including EBV, CMV, and even SARS-CoV2 can cause these errors. This in combination with genetic factors can lead to rheumatic disease development. This research aims to provide a brief review of the role of viruses in the outset and development of AIRDs.

This phase I trial assessed the safety and potential efficacy of monthly 3 dose intravenous infusion of allogeneic bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs) in refractory rheumatoid arthritis (RA) patients over 24 weeks.

Six patients with refractory RA received BM-cMSC infusions at one-month intervals over a 24-week period. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Clinical efficacy was assessed using the Visual Analog Scale (VAS), Simple and Clinical Disease Activity Indices (SDAI/CDAI), Health Assessment Questionnaire (HAQ), and American College of Rheumatology (ACR) response criteria. Serological makers including: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IL-10, IL-17, TNF-α, and Treg/Th17 ratios were measured.

BM-cMSC infusions were well-tolerated, with no SAEs reported. VAS scores improved in three patients, with two achieving sustained pain relief and quality-of-life enhancement. Four patients met ACR20 at week 16, while SDAI and CDAI scores indicated disease activity reduction in three patients. Anti-CCP and RF levels showed variable responses, with some increases not consistently correlating with clinical outcomes. Serological biomarkers showed mixed results; IL-10 increased in five patients, while pro-inflammatory markers TNF-α and IL-17 decreased in the same individuals.

BM-cMSC therapy demonstrated a favorable safety profile and potential efficacy in managing refractory RA. While preliminary results are promising, further studies with larger cohorts and long-term follow-up are needed to validate these findings and optimize therapeutic strategies.

IRCT20080728001031N29.

This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients.

Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated.

Multivariate analysis identified history of previous serious infection, age > 60 years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P < 0.001 and 0.003; respectively).

Age > 60 years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory polyarthritis and extra-articular involvement. Extraarticular manifestations of RA can include involvement of the skin, eye, heart, lungs, and others. RA is associated with a broad spectrum of pleuropulmonary involvement, with interstitial lung disease (ILD) and pleural disease being the most common. COVID-19 infection cross-talks with RA at various stages of pathogenesis. The clinical course and outcome of COVID-19 infection in RA patients may be ameliorated due to various reasons including anti-rheumatic drugs; however, COVID-19 vaccination provides additional protection to high-risk patients compared to non-vaccinated patients. Here, we present a case of end-stage RA-associated ILD who presented with the chief complaint of shortness of breath and tested positive for COVID-19. She was a lung transplant candidate on long-term antifibrotic medication nintedanib for interstitial fibrosis. The patient survived the initial acute hypoxemic respiratory failure, which might be attributed to being fully vaccinated for COVID-19.

The impact of rheumatic diseases, long-term medication, and vaccination on COVID-19 severity remain insufficiently understood, hindering effective patient management. This study aims to investigate factors influencing COVID-19 severity in Chinese rheumatic patients and to provide real-world evidence for patient care.

We conducted a retrospective observational study consisting of two cohorts, followed by a nested case-control analysis. The outpatient cohort included non-severe COVID-19 patients, while the inpatient cohort included consecutive severe COVID-19 inpatients. Additionally, rheumatic patients from both cohorts were included for the nested case-control study. Clinical information was obtained from electronic medical records and surveys.

A total of 749 outpatients and 167 inpatients were enrolled. In the outpatient cohort, rheumatic diseases were identified as a risk factor for the severity of dyspnea (No rheumatic disease: OR = 0.577, 95% CI = 0.396-0.841, p = .004), but not for mortality, length of hospitalization, or hospitalization costs in the inpatient cohort. Long-term glucocorticoids use was identified as an independent risk factor for severity of dyspnea in rheumatic patients (OR = 1.814, 95% CI = 1.235-2.663, p = .002), while vaccination and immunosuppressant treatment showed no association. Vaccination was identified as a protective factor against hospitalization due to COVID-19 in patients with rheumatic diseases (OR = 0.031, 95% CI = 0.007-0.136, p < .001), whereas long-term glucocorticoids and immunosuppressant treatment showed no association.

Rheumatic diseases and long-term glucocorticoids use are significant risk factors for COVID-19 severity in the Chinese population, whereas emphasizing the protective effects of vaccines against COVID-19 severity is crucial. Additionally, the investigation provides preliminary support for the concept that long-term immunosuppressant therapy does not necessarily require additional prescription adjustments.

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

Rheumatoid arthritis (RA), a chronic and systemic autoimmune disease that primarily attacks the joints around the body, is affecting a large number of people worldwide through severe symptoms and complications. Therefore, it is crucial to understand these patients' problems and support needs such that effective strategies or solutions can be made to improve their long-term treatment experience. In this paper, we present an in-depth study that is based on the structural topic model to uncover the themes and concerns in online RA posts from Reddit, an American social news aggregation, content rating, and discussion website. In addition, we compared the topic prevalence differences before and after the COVID-19 pandemic to understand the impact of the pandemic on these online users. This study demonstrates the potential of using text-mining techniques on social media data to learn the treatment experiments of RA patients.

Patients with established rheumatic disorders may develop complications of macrophage activation syndrome due to severe flares of the underlying disease (adult-onset Still's disease, SLE); however, in most other rheumatic disorders, MAS develops in association with identified viral or other infectious triggers. It is therefore important to pursue appropriate studies to identify potential infectious triggers in rheumatic disease patients who develop MAS. Management is best directed toward treatment of the triggering infections and combinations of high-dose corticosteroids, calcineurin inhibitors, and biologic therapies targeting IL-1 and/or IL-6 to suppress the associated cytokine storm.

Musculoskeletal symptoms are commonly reported following acute COVID-19. It is unclear whether those with musculoskeletal symptoms subsequently develop inflammatory rheumatic musculoskeletal disease (iRMD). This review seeks to identify evidence for an association between acute COVID-19 and subsequent iRMD diagnosis.

A rapid review of the literature using a systematic search of Medline, EMBASE and two COVID-19 databases was undertaken until August 2022. Case studies, case series, cross-sectional, case-control, and cohort studies reporting patients with an incident iRMD following COVID-19 were included. Title and abstract screening were conducted by one reviewer and full text screening by two reviewers. Data extraction and quality appraisal were by one reviewer, with a second verifying. Study-type specific critical appraisal tools were used.

Results were narratively synthesized. A total of 80 studies were included (69 case reports, 10 case series and 1 cross-sectional study). Commonly reported iRMDs were "reactive arthropathies" (n = 47), "inflammatory arthropathies unspecified" (n = 18), rheumatoid arthritis (n = 12) and systemic lupus erythematosus (n = 11). The cross-sectional study reported 37% of those with COVID-19 developed "post COVID arthritis." Time from diagnosis of COVID-19 to iRMD presentation ranged from 0 to 120 days. Several mechanisms were proposed to explain the association between COVID-19 and iRMD development: autoimmune processes, aberrant inflammatory responses, colonization of joint spaces, direct damage from the severe acute respiratory syndrome coronavirus 2 virus and genetic predisposition.

The level of evidence of the studies included in this review was low and the quality generally poor. Prospective observational studies are required to confirm associations and likely impact of post COVID-19 iRMDs at a population level.

Background: The breakthrough development of novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines and oral antivirals have played a critical role in curtailing the spread of the pandemic and dramatically reducing the morbidity and mortality rates among those infected. Among these oral antivirals, nirmatrelvir/ritonavir (NR) has been repurposed successfully for use against coronavirus disease-2019 (COVID-19) and is now readily available on the market with promising therapeutic effects. The availability of convenient and effective NR treatments for COVID-19 greatly mitigates the severity of the epidemic and contributes to an early end to the pandemic. Furthermore, certain patient subgroups, specifically those with rheumatic disease (RD) who are currently undergoing intensive immunodeficiency and/or immunosuppressive treatments, continue to be vulnerable and at a higher risk of experiencing severe consequences from COVID-19. Additionally, it has also been observed that NR exhibited prevalent drug-drug interactions of clinical significance, and more instances of COVID-19 rebound were being recognized with increasing frequency. Methods: A retrospective cohort study was conducted on a real-world RD population who were infected with SARS-CoV-2 and treated with NR. The time of symptom resolution, length of hospitalization, and response rate were assessed. Results were compared among the standard regimen and non-standard regimen groups, early NR regimen and late NR regimen groups, and the NR indication regimen and NR non-indication regimen groups. During the course, all grades of adverse drug reactions (ADRs) directly associated with NR administration and associated with drug-drug interactions (DDIs) were also monitored. Results: A total of 32 patients with RD, who were infected with SARS-CoV-2 and received NR, were retrospectively identified and divided into different groups. We found that the standard regimen group and the early NR regimen group had a shorter median time of symptom resolution compared to the control group [9.0 (interquartile range [IQR], 8.3-11.3) vs. 21.5 (IQR16.0-24.0) days, p < 0.001 and 9.0 (IQR 8.3-11.3) vs. 23.0 (IQR 18.0-24.0) days, p = 0.0]. We further found that even if the NR administration time exceeds 5 days, patients with RD who receive the NR indication regimen can still derive certain benefits from it. The proportion of patients who showed symptom improvement was higher in the NR indication regimen compared to the NR non-indication regimen group (n = 13/17 vs. 3/6, 76.5% vs. 50.0%) at the end of follow-up, and there was a statistical difference (p = 0.0) in the response rate of patients between the two groups. We also analyzed the effect of comorbidities on patient response rates and found that the percentage of patients who showed symptom improvement was higher in the group with <4 comorbidities compared to the group with ≥ 4 comorbidities (n = 7/7 vs. 16/25, 100.0% vs. 64.0%) at the end of follow-up. During the course, all grades of ADRs and grade ≥3ADRs directly associated with NR administration were not observed in any of the 32 cases. Despite discontinuing warfarin prior to NR application (using NR immediately on the first day of warfarin withdrawal), one patient still experienced an increased international normalized ratio [INR, 5.32(0.90-1.20)] and coagulation disorders (weak positive fecal occult blood test) on the second day after using NR. The INR levels decreased to nearly normal values, and coagulation disorders returned to normal after 2 days of discontinuing NR (the seventh day after the initial administration of NR). Conclusion: We showed NR therapy to be associated with a favorable outcome and an acceptable safety profile in an immunosuppressed population with RD during the Omicron surge. Early use of NR (within 5 days of symptom onset) could improve the prognosis of patients. NR administration for symptoms and confirmed SARS-CoV-2 infection after >5 days may also mitigate progression to severe disease and is a viable strategy. Our results highlight the importance of early utilization and/or NR indication, which may yield clinical advantages for patients with RD infected with SARS-CoV-2.

During the COVID-19 pandemic, anti-SARS-CoV-2 vaccines were quickly developed and administered to the population worldwide. As is expected with new vaccine products, adverse reactions following immunization have been reported, namely, the development and/or exacerbation of autoimmune/autoinflammatory diseases, including rheumatic diseases. Here, we report a clinical case of a 56-year-old woman with a 44-year history of moderate-to-severe plaque psoriasis under treatment with an anti-tumor necrosis factor alpha biosimilar (adalimumab) with good control of skin disease and without rheumatic involvement to date who came to us with complaints of migratory polyarthralgia starting one week after receiving the second dose of the BNT162b2 COVID-19 mRNA vaccine. The condition progressed over the following months and a diagnosis of psoriatic arthritis was established. Biologic treatment was switched to an anti-interleukin 17A (secukinumab), with a very good clinical cutaneous and articular response, which was sustained up to the present moment. The mechanisms behind the exacerbation or new-onset of autoimmune/autoinflammatory diseases after receiving anti-COVID-19 vaccines are not yet fully understood, requiring further investigation. It is also not known whether rheumatic symptoms post-COVID-19 infection will have similar mechanisms to rheumatic symptoms post-anti-COVID-19 vaccination. With the continuing worldwide vaccination against SARS-CoV-2, clinicians need to be prepared to discuss the risks and benefits of vaccination and should be aware that it may cause or exacerbate immune disorders such as psoriatic arthritis, warranting close follow-up in terms of disease progression and treatment.

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and βdiff (β difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005-2007 to 1.55% in 2016-2019 and OA: from 9.75% in 2005-2007 to 8.27% in 2016-2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19-60 years, ratio of ORs: 1.222; 95% CI 1.011-1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007-1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119-1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence.

Many studies have shown an association between COVID-19 and autoimmune diseases (ADs). Studies on COVID-19 and ADs have also increased significantly, but there is no bibliometric analysis to summarize the association between COVID-19 and ADs. The purpose of this study was to perform a bibliometric and visual analysis of published studies related to COVID-19 and ADs.

Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools Co-Occurrence13.2 (COOC13.2), VOSviewer, CiteSpace, and HistCite for analysis.

A total of 1736 related kinds of papers were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, the author is Yehuda Shoenfeld from Israel, and the journal is Frontiers in Immunology. Research hotspots include immune responses (such as cytokines storm), multisystem ADs (such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis), treatment modalities (such as hydroxychloroquine, rituximab), vaccination and autoimmune mechanisms (such as autoantibodies, molecular mimicry). The future research direction may be the mechanisms and treatment ideas of the association between ADs and COVID-19 (such as NF-κB, hyperinflammation, antiphospholipid antibodies, neutrophil extracellular traps, granulocyte-macrophage colony-stimulating factor), other cross-diseases of COVID-19 and ADs (such as inflammatory bowel disease, chronic mucocutaneous candidiasis, acute respiratory distress syndrome).

The growth rate of publications regarding ADs and COVID-19 has risen sharply. Our research results can help researchers grasp the current status of ADs and COVID-19 research and find new research directions in the future.

The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like activities have shown potent antiviral effects and the ability to inhibit oxidative stress and cytokines and provide immunotherapeutic effects while also safeguarding diverse cell populations. These adaptable nanozymes have already exhibited efficacy in treating common types of arthritis, and their distinctive synergistic therapeutic effects offer great potential in the fight against arthritis associated with COVID-19. In this comprehensive review, we explore the potential of nanozymes in alleviating arthritis following SARS-CoV-2 infection by neutralizing the underlying factors associated with the disease. We also provide a detailed analysis of the common therapeutic pathways employed by these nanozymes and offer insights into how they can be further optimized to effectively address COVID-19-associated arthritis.

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of confirmed cases and deaths worldwide. Understanding the biological mechanisms of SARS-CoV-2 infection is crucial for the development of effective therapies. This study conducts differential expression (DE) analysis, pathway analysis, and differential network (DN) analysis on RNA-seq data of four lung cell lines, NHBE, A549, A549.ACE2, and Calu3, to identify their common and unique biological features in response to SARS-CoV-2 infection. DE analysis shows that cell line A549.ACE2 has the highest number of DE genes, while cell line NHBE has the lowest. Among the DE genes identified for the four cell lines, 12 genes are overlapped, associated with various health conditions. The most significant signaling pathways varied among the four cell lines. Only one pathway, "cytokine-cytokine receptor interaction", is found to be significant among all four cell lines and is related to inflammation and immune response. The DN analysis reveals considerable variation in the differential connectivity of the most significant pathway shared among the four lung cell lines. These findings help to elucidate the mechanisms of SARS-CoV-2 infection and potential therapeutic targets.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.

We aimed to investigate the role of rheumatoid arthritis (RA) with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) exposure in COVID-19 outcomes.

Our study retrieved data from the US Collaborative Network in TriNetX between 1 January 2018 and 31 December 2022. We investigated b/tsDMARD use for RA: interleukin 6 inhibitor (IL-6i), Janus-associated kinase inhibitors (JAKi) or tumour necrosis factor-alpha inhibitors (TNFi, reference group). The outcomes of COVID-19 were the incidence of infection and adverse outcomes (hospitalisation, critical care services, mechanical ventilation and mortality). The HR and 95% CI of the outcomes were calculated between propensity score-matched (PSM) patients with different b/tsDMARDs.

After PSM, 2676 JAKi vs 2676 TNFi users and 967 IL-6i vs 967 TNFi users were identified. As for COVID-19 incidence, JAKi users did not reach statistical significance (HR: 1.058, 95% CI: 0.895 to 1.250) than TNFi users. RA with JAKi users had a significant risk for hospitalisation (HR: 1.194, 95% CI: 1.003 to 1.423), mortality (HR: 1.440, 95% CI: 1.049 to 1.976) and composite adverse outcomes (HR: 1.242, 95% CI: 1.051 to 1.468) compared with TNFi users. Mortality risk tended to be significantly higher in the JAKi group without COVID-19 vaccination (HR: 1.511, 95% CI: 1.077 to 2.121). IL-6i users compared with TNFi users did not have the above findings.

RA with JAKi users had a significant risk for hospitalisation, mortality or composite adverse outcomes, especially higher mortality among those without COVID-19 vaccination. COVID-19 vaccination should be encouraged in these target cohorts. When using JAKi for patients with RA, clinicians should be vigilant about these adverse outcomes to prevent their occurrence or detect them early for early intervention.

Cases of coronavirus disease 2019 (COVID-19) appear with a very diverse pattern of health manifestation, in which the immune system plays a major driver of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection outcomes. The uncontrolled immune response of SARS-CoV-2 infection could possibly lead to autoimmune diseases, as we observed increased cases of pemphigus vulgaris (PV) post-COVID-19 infection. PV is an autoimmune life-threatening mucocutaneous disease that is very rarely induced by certain drugs or substance. The link between COVID-19 infection and autoimmune diseases is still unknown. This study outline the possible link with PV following infection of COVID-19. A case series of three females and one male between the ages of 33 and 57 with no history of drug-induced illness or allergy were observed in our current case series. All patients previously contracted SARS-CoV-2. The lesions were treated with systemic and oral corticosteroid was given as a basic treatment for PV lesions. Immunomodulator agent was added as an adjunct to reduce the effects of steroid and to decrease the severity of PV. In conclusion, clinicians should be vigilant of the potential emergence of autoimmune reaction following the COVID-19 pandemic. Further investigation is required to unfold the unclear mechanism of PV induced by SARS-CoV-2. We hypothesized that the genetic aberrance inferred by this viral infection might trigger autoimmune diseases and may not limit to PV.

To investigate the outcomes of COVID-19-related hospitalizations among patients with autoimmune rheumatic diseases (ARDs) in the United States in 2020. The primary outcome was in-hospital mortality, and secondary outcomes included intubation rate, length of hospital stay (LOS), and total hospital charges (THCs).

Data for the study were obtained from the National Inpatient Sample database and included patients who were hospitalized with a principal diagnosis of COVID-19. Univariable and multivariable logistic regression analyses were conducted to calculate odds ratios for the outcomes, adjusting for age, sex, and comorbidities.

Out of the 1,050,720 COVID-19 admissions, 30,775 had an ARD diagnosis. The unadjusted analysis showed higher mortality (12.21%) and intubation (9.2%) rates in the ARD group compared with the non-ARD group (mortality rate: 11.14%, P = 0.013; intubation rate: 8.5%, P = 0.048). However, this difference was not significant after adjusting for confounding factors. The mean LOS and THCs did not differ significantly between the two groups. Among all ARD subgroups, the vasculitis group had significantly higher intubation rate, LOS, and THC.

The study suggests that ARD is not associated with an increased risk of mortality or worse outcomes among patients hospitalized with COVID-19 after adjusting for confounding factors. However, the vasculitis group had poorer outcomes during COVID-19 hospitalizations. Further studies are needed to evaluate the effect of ARD activity and immunosuppressants on outcomes. Additionally, more research is required to investigate the relationship between COVID-19 and vasculitis.

Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population.

In this study, we used bioinformatic approaches to explore common pharmacological targets and signaling pathways between RA and mild-to-moderate COVID-19, and to assess the potential mechanisms of in the treatment of patients with both diseases. Beside, molecular docking was used to explore the molecular interactions between GSZD and SARS-CoV-2 related proteins.

Results showed that 1183 common targets were found in mild-to-moderate COVID-19 and RA, of which TNF was the most critical target. The crosstalk signaling pathways of the two diseases focused on innate immunity and T cells pathways. In addition, GSZD intervened in RA and mild-to-moderate COVID-19 mainly by regulating inflammation-related signaling pathways and oxidative stress. Twenty hub compounds in GSZD exhibited good binding potential to SARS-CoV-2 spike (S) protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro) and human angiotensin-converting enzyme 2 (ACE2), thereby intervening in viral infection, replication and transcription.

This finding provides a therapeutic option for RA patients against mild-to-moderate COVID-19, but further clinical validation is still needed.

SARS-CoV-2 virus has attracted a lot of attention globally due to the autoimmune and inflammatory processes that were observed during the development of Covid-19 disease. Excessive activation of immune response and triggering of autoantibodies synthesis as well as an excessive synthesis of inflammatory cytokines and the onset of cytokine storm has a vital role in the disease outcome and the occurring autoimmune complications. This scenario is reminiscent of infiltration of lymphocytes and monocytes in specific organs and the increased production of autoantibodies and chemoattractants noted in other inflammatory and autoimmune diseases. The main goal of this study is to investigate the complex inflammatory processes that occur in Covid-19 disease and to find similarities with other inflammatory diseases such as multiple sclerosis (MS), acute respiratory distress syndrome (ARDS), rheumatoid arthritis (RA) and Kawasaki syndrome to advance existing diagnostic and therapeutic protocols. The therapy with Interferon-gamma (IFN-γ) and the use of S1P receptor modulators showed promising results. However, there are many unknowns about these mechanisms and possible novel therapies. Therefore, the inflammation and autoimmunity triggered by Covid-19 should be further investigated to improve existing diagnostic procedures and therapeutic protocols for Covid-19.

Coronavirus Disease (COVID-19) may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. Using the latest data from COVID-19 host genetics consortium and consortia on RA and SLE, we conducted a genome-wide cross-trait analysis to examine the shared genetic etiology between COVID-19 and RA/SLE and evaluated their causal associations using bidirectional Mendelian randomization (MR). The cross-trait meta-analysis identified 23, 28, and 10 shared genetic loci for severe COVID-19, COVID-19 hospitalization, and SARS-CoV-2 infection with RA, and 14, 17, and 7 shared loci with SLE, respectively. Co-localization analysis identified five causal variants in TYK2, IKZF3, PSORS1C1, and COG6 for COVID-19 with RA, and four in CRHR1, FUT2, and NXPE3 for COVID-19 with SLE, involved in immune function, angiogenesis and coagulation. Bidirectional MR analysis suggested RA is associated with a higher risk of COVID-19 hospitalization, and COVID-19 is not related to RA or SLE. Our novel findings improved the understanding of the genetic etiology shared by COVID-19, RA and SLE, and suggested an increased risk of COVID-19 hospitalization in people with higher genetic liability to RA.

Hydroxychloroquine (HCQ) is a known disease-modifying antirheumatic drug for rheumatoid arthritis. It is also being used in viral arthritis on many occasions. HCQ is also being used to treat coronavirus disease 2019, but the results are not satisfactory. HCQ has been shown to have antiviral effects. In this context, we have a hypothesis that HCQ may be used as a treatment option in post-coronavirus disease 2019 arthritis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Cytokine patterns and immune activation in patients with Coronavirus 2019 (COVID-19) seem to resemble the case of rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Biological drugs, such as anti-tumor necrosis factor α (TNFα) and interleukin (IL) inhibitors, appear to be protective against adverse outcomes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, these treatments are associated with an increased risk of secondary infections. The aim of the study was to examine the association between the use of immunomodulatory drugs and the risk of SARS-CoV-2-associated positivity, hospitalization and death compared to other commonly prescribed treatment regimens among patients with immune-mediated inflammatory diseases.

All patients with RA, Psoriasis and IBD were included in this observational analysis and treated with anti-TNFα, IL-inhibitors, Methotrexate (MTX) and Sulfasalazine drugs during the year 2020-2021. The population consisted of 932 patients and demographic, clinical and pharmacological data were analyzed.

Although no significant differences were observed between patients treated with biological and synthetic drugs in terms of hospitalization and death, the multivariate logistic model showed that the type of drug influences the possibility of COVID-19 positivity.

The results of this analysis support the use of biological drugs and justify further research investigating the association of these biological therapies with COVID-19 outcomes.

COVID-19 is a recent pandemic that mandated the scientific society to provide effective evidence-based therapeutic approaches for the prevention and treatment for such a global threat, especially to those patients who hold a higher risk of infection and complications, such as patients with autoimmune diseases and cancer. Recent research has examined the role of various fat-soluble vitamins (vitamins A, D, E, and K) in reducing the severity of COVID-19 infection. Studies showed that deficiency in fat-soluble vitamins abrogates the immune system, thus rendering individuals more susceptible to COVID-19 infection. Moreover, another line of evidence showed that supplementation of fat-soluble vitamins during the course of infection enhances the viral clearance episode by promoting an adequate immune response. However, more thorough research is needed to define the adequate use of vitamin supplements in cancer and autoimmune patients infected with COVID-19. Moreover, it is crucial to highlight the vitamin-drug interactions of the COVID-19 therapeutic modalities and fat-soluble vitamins. With an emphasis on cancer and autoimmune patients, the current review aims to clarify the role of fat-soluble vitamins in SARS-CoV-2 infection and to estimate the risk-to-benefit ratio of a fat-soluble supplement administered to patients taking FDA-approved COVID-19 medications such as antivirals, anti-inflammatory, receptor blockers, and monoclonal antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19). Staphylococcus aureus is one of the most common pathogenic bacteria in humans, rheumatoid arthritis (RA) is among the most prevalent autoimmune conditions. RA is a significant risk factor for SARS-CoV-2 and S. aureus infections, although the mechanism of RA and SARS-CoV-2 infection in conjunction with S. aureus infection has not been elucidated. The purpose of this study is to investigate the biomarkers and disease targets between RA and SARS-CoV-2 and S. aureus infections using bioinformatics analysis, to search for the molecular mechanisms of SARS-CoV-2 and S. aureus immune escape and potential drug targets in the RA population, and to provide new directions for further analysis and targeted development of clinical treatments.

The RA dataset (GSE93272) and the S. aureus bacteremia (SAB) dataset (GSE33341) were used to obtain differentially expressed gene sets, respectively, and the common differentially expressed genes (DEGs) were determined through the intersection. Functional enrichment analysis utilizing GO, KEGG, and ClueGO methods. The PPI network was created utilizing the STRING database, and the top 10 hub genes were identified and further examined for functional enrichment using Metascape and GeneMANIA. The top 10 hub genes were intersected with the SARS-CoV-2 gene pool to identify five hub genes shared by RA, COVID-19, and SAB, and functional enrichment analysis was conducted using Metascape and GeneMANIA. Using the NetworkAnalyst platform, TF-hub gene and miRNA-hub gene networks were built for these five hub genes. The hub gene was verified utilizing GSE17755, GSE55235, and GSE13670, and its effectiveness was assessed utilizing ROC curves. CIBERSORT was applied to examine immune cell infiltration and the link between the hub gene and immune cells.

A total of 199 DEGs were extracted from the GSE93272 and GSE33341 datasets. KEGG analysis of enrichment pathways were NLR signaling pathway, cell membrane DNA sensing pathway, oxidative phosphorylation, and viral infection. Positive/negative regulation of the immune system, regulation of the interferon-I (IFN-I; IFN-α/β) pathway, and associated pathways of the immunological response to viruses were enriched in GO and ClueGO analyses. PPI network and Cytoscape platform identified the top 10 hub genes: RSAD2, IFIT3, GBP1, RTP4, IFI44, OAS1, IFI44L, ISG15, HERC5, and IFIT5. The pathways are mainly enriched in response to viral and bacterial infection, IFN signaling, and 1,25-dihydroxy vitamin D3. IFI44, OAS1, IFI44L, ISG15, and HERC5 are the five hub genes shared by RA, COVID-19, and SAB. The pathways are primarily enriched for response to viral and bacterial infections. The TF-hub gene network and miRNA-hub gene network identified YY1 as a key TF and hsa-mir-1-3p and hsa-mir-146a-5p as two important miRNAs related to IFI44. IFI44 was identified as a hub gene by validating GSE17755, GSE55235, and GSE13670. Immune cell infiltration analysis showed a strong positive correlation between activated dendritic cells and IFI44 expression.

IFI144 was discovered as a shared biomarker and disease target for RA, COVID-19, and SAB by this study. IFI44 negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation and is an important molecular target for SARS-CoV-2 and S. aureus immune escape in RA. Dendritic cells play an important role in this process. 1,25-Dihydroxy vitamin D3 may be an important therapeutic agent in treating RA with SARS-CoV-2 and S. aureus infections.

COVID-19 is a disease that is challenging science, health-care systems, and humanity. An astonishingly wide spectrum of manifestations of multi-organ damage, including musculoskeletal, can be associated with SARS-CoV-2.

In the acute phase of COVID-19, fatigue, myalgia, and arthralgia are the most common musculoskeletal symptoms.

Post-COVID-19 syndrome is a group of signs and symptoms that are present for >12 weeks. The associated musculoskeletal manifestations are fatigue, arthralgia, myalgia, new-onset back pain, muscle weakness, and poor physical performance.

Data on COVID-19 complications are growing due to large absolute numbers of cases and survivors in these 2 years of the pandemic. Additional musculoskeletal manifestations encountered are falls by the elderly, increased mortality after hip fracture, reduced bone mineral density and osteoporosis, acute sarcopenia, rhabdomyolysis, Guillain-Barré syndrome, muscle denervation atrophy, fibromyalgia, rheumatological disease triggering, septic arthritis, adhesive capsulitis, myositis, critical illness myopathy, onset of latent muscular dystrophy, osteonecrosis, soft-tissue abscess, urticarial vasculitis with musculoskeletal manifestations, and necrotizing autoimmune myositis.

A wide range of signs and symptoms involving the musculoskeletal system that affect quality of life and can result in a decrease in disability-adjusted life years. This powerful and unpredictable disease highlights the importance of multimodality imaging, continuing education, and multidisciplinary team care to support preventive measures, diagnosis, and treatment.

T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19.

We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry.

Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3+CD4+CD45RO-CD62L- and CD3+CD8+CD45RO-CD62L- T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3+CD4+CD45RO-CD62L+ and CD3+CD8+CD45RO-CD62L+ T cell frequencies and increased CD3+CD8+CD45RO-CD62L- cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets.

The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19.

In "Cellular Immunology and COVID-19" (a Special Issue of Cells), a panel of leading scientists provides an exhaustive overview of the different aspects of the immune mechanisms underlying COVID-19 [...].