Managing Patients with Immune-Mediated Inflammatory Diseases on Disease-Modifying Antirheumatic Drug Therapy in a COVID-19 Endemic World: A Narrative Review and Expert Insights (preprint)

During the coronavirus disease 2019 (COVID-19) pandemic, individuals with immune-mediated inflammatory diseases (IMIDs), such as systemic lupus erythematosus and rheumatoid arthritis, face a heightened risk of infection and severe outcomes due to immunological alterations resulting from their underlying conditions and immunosuppressive treatments. Even as the pandemic has transitioned to an endemic state, it remains crucial to recognize that these patients continue to be at risk. In this narrative review, we analyzed existing literature to explore the impact of IMIDs, clinical risk factors, and the influence of immunosuppressive therapies on COVID-19-related risks and outcomes. Notably, certain disease-modifying antirheumatic drugs (DMARDs), like rituximab, are associated with worse COVID-19 outcomes, and rituximab-treated patients show impaired immune responses to COVID-19 vaccination. Additionally, we outline the diverse effects of glucocorticoids on COVID-19 outcomes and management. To highlight real-life challenges faced by clinicians caring for patients with IMIDs, we present an illustrative scenario that underscores the importance of effective vaccination, timely boosting, and additional mitigation strategies against COVID-19. Given the clinical heterogeneity and diverse disease states within IMIDs, it is crucial to understand the ongoing implications and risks associated with COVID-19 in these patients, to guide the implementation of appropriate measures and optimize care and outcomes in the current endemic era.

Exposure to air pollution in epidemiological studies in Kuwait: A systematic review (preprint)

Objective To systematically review the epidemiological studies of human exposure to air pollution in Kuwait. Methods Specific keywords related to air pollution and health effects in Kuwait were systematically searched using PubMed and BASE search engines for published research in English language from the year 1990 up to June 2020. Non eligible studies were those which published in non-English studies, studies on animals, plants, exposure to pollutants other that air pollutants, studies related to oil fires caused by Iraqi invasion to Kuwait in 1991. After duplicates were removed, titles and abstracts of eligible studies were screened and full text of publications meeting the inclusion criteria was read. Non-epidemiological studies were included only to compare their numbers to the epidemiological studies, and to help in future studies. Results Total of 85 studies including epidemiological and non-epidemiological studies, only 8 of them found to be an epidemiological study, which 4 of them concerned with mortality and 3 with morbidity, and 1 with both morbidity and mortality. Two of these studies concern with respiratory disease, 1 of them concerned with atopic dermatitis and was the only study measured indoors (i.e. house), and 1 study concerned with rheumatoid arthritis. One study measured ETS, 4 studies measured dust, 2 studies measured PM10 and PM2.5, and 1 study measured NO2, SO2, O3, CO. All studies found that exposure to air pollution has adverse effect on health problems (i.e. respiratory problems, atopic dermatitis, rheumatoid arthritis) and mortality except one study found no significant correlation between exposure to air pollution (i.e. dust) and mortality. Conclusion Epidemiological studies related to human exposure to air pollution in Kuwait are underestimated and insufficient, there are extremely limited studies that cannot be compared to each other. Since currently Kuwait have many major constructions in major roads in and out the capital which alters the air pollution, adding to that the new study which found that the new current global epidemic namely coronavirus COVID-19 is correlated to air pollution (i.e. NO2), new researches need to be done measuring the different pollutants in both indoor and outdoor exposure examining different health problems, these researches need to be done during and after these circumstances for comparison.

COVID-19 Impact on Patients with Immune-Mediated Rheumatic Disease: A Comparative Study of Disease Activity and Psychological Well-Being Over Six Months (preprint)

Objectives: To compare the impact of COVID-19 on clinical status and psychological condition in patients with immune-mediated rheumatic diseases (IMRD) infected by SARS-CoV-2 with IMRD controls not infected, during a 6-month follow-up. Methods: The ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. The FACIT-F (Functional Assessment of Chronic Illness Therapy) and DASS 21 (Depression, Anxiety and Stress Scale - 21 Items) questionnaires were also applied at 6 months after COVID-19 in both groups before large-scale vaccination. The significance level was set as p<0.05, with a 95% confidence interval. Results: A total of 601 patients were evaluated, being 321 cases (IMRD COVID-19+) and 280 controls (IMRD COVID-19 -), predominantly female with similar median age. No significant differences were noted in demographic data between the groups, including comorbidities, disease duration, and IMRD. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. While mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR=7.15), while TNF inhibitors showed a protective effect (OR=0.51). Comparing SLEDAI pre- and post-COVID-19, a minority showed increased scores, with few requiring treatment changes. Fatigue, depression, anxiety, and stress were significantly higher in cases compared to controls. Worsening disease activity post-COVID correlated with worsened FACIT-F and DASS-21 stress scale in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity or psychological assessments. Conclusions: Post-COVID-19 IMRD patients show significant psychological well-being deterioration despite similar disease activity scores. The variability in reports on IMRD flares and the potential trigger of SARS-CoV-2 for autoimmune manifestations underline the need for detailed clinical assessment and a comprehensive approach to managing them.

Baricitinib as a novel treatment for bullous pemphigoid: a case series report (preprint)

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

Immunomodulators and risk for breakthrough infection after third COVID-19 mRNA vaccine among patients with rheumatoid arthritis: A cohort study (preprint)

Objectives: To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi). Methods: We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston, MA, USA. Patients were followed from the date of 3rd vaccine dose until breakthrough COVID-19, death, or end of follow-up (18/Jan/2023). Covariates included demographics, lifestyle, comorbidities, and prior COVID-19. We used Cox proportional hazards models to estimate breakthrough COVID-19 risk by immunomodulator drug class. We used propensity score (PS) overlap-weighting to compare users of CD20i vs. TNFi. Results: We analyzed 5781 patients with RA that received 3 mRNA vaccine doses (78.8% female, mean age 64.2 years). During mean follow-up of 12.8 months, 1173 (20.2%) had breakthrough COVID_19. Use of CD20i (adjusted HR 1.74, 95%CI 1.30-2.33) and glucocorticoid monotherapy (adjusted HR 1.47, 95%CI 1.09-1.98) were each associated with breakthrough COVID-19 compared to TNFi use. In the PS overlap-weighted analysis, CD20i users also had higher breakthrough COVID-19 risk than TNFi users (HR 1.62, 95%CI 1.02-2.56). A sensitivity analysis excluding patients with cancer or interstitial lung disease yielded similar findings. Conclusions: We identified CD20i and glucocorticoid monotherapy as risk factors for breakthrough COVID-19 among patients with RA after a 3rd vaccine dose. This contemporary study highlights the real-world impact of blunted immune responses in these subgroups and the need for effective risk mitigation strategies.

Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study. (preprint)

Introduction Healthcare workers (HCWs) from an interprovincial Canadian cohort were asked to give serial blood samples to identify factors associated with anti-receptor binding domain (anti-RBD) IgG response to the SARS-CoV-2 virus. Methods Members of the HCW cohort donated blood samples four months after their first SARS-CoV-2 immunization and again at 7, 10 and 13 months. Date and type of immunizations and dates of SARS-CoV-2 infection were collected at each of four contacts, together with information on immunologically-compromising conditions and current therapies. Blood samples were analyzed centrally for anti-RBD IgG and anti-nucleocapsid IgG (Abbott Architect, Abbott Diagnostics). Records of immunization and SARS-CoV-2 testing from public health agencies were used to assess the impact of reporting errors on estimates from the random-effects multivariable model fitted to the data. Results 2752 of 4567 vaccinated cohort participants agreed to donate at least one blood sample. Modelling of anti-RBD IgG titer from 8903 samples showed an increase in IgG with each vaccine dose and with first infection. A decrease in IgG titer was found with the number of months since vaccination or infection, with the sharpest decline after the third dose. An immunization regime that included mRNA1273 (Moderna) resulted in higher anti-RBD IgG. Participants reporting multiple sclerosis, rheumatoid arthritis or taking selective immunosuppressants, tumor necrosis factor inhibitors, calcineurin inhibitors and antineoplastic agents had lower anti-RBD IgG. Supplementary analyses showed higher anti-RBD IgG in those reporting side-effects of vaccination, no relation of anti-RBD IgG to obesity and lower titers in women immunized early in pregnancy. Sensitivity analysis results suggested no important bias in the self-report data. Conclusion Creation of a prospective cohort was central to the credibility of results presented here. Serial serology assessments, with longitudinal analysis, provided effect estimates with enhanced accuracy and a clearer understanding of medical and other factors affecting response to vaccination.

COVID-19 vaccines and autoimmune disorders: A scoping review protocol (preprint)

Background - Two years into the global vaccination program, important questions about the association between COVID-19 vaccines and autoimmune diseases have arisen. A growing number of reports have documented associations between COVID-19 vaccination and autoimmunity, suggesting, for example, a causal link between vaccination and new-onset and/or relapsing autoimmune disorders such as type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Graves disease, and Hashimoto s thyroiditis. These autoimmune phenomena have occurred with various COVID-19 vaccines and research is required to elucidate the underlying mechanisms and causal directions, for example, whether persons with no history of autoimmune disorders may experience them upon vaccination or persons with autoimmune disorders may experience exacerbation or new adverse events post-vaccination. Methods and analysis - Specific objectives of this scoping review will address the following questions: Can COVID-19 vaccination trigger and/or exacerbate autoimmune disorders? Are persons with autoimmune disorders at higher risk of experiencing additional autoimmune disorders? What are the mechanisms connecting autoimmune disorders with COVID-19 vaccination? Can COVID-19 vaccination interact with immunosuppressive therapy in persons with autoimmune disorders? Does the risk of autoimmune disorders following COVID-19 vaccination differ by vaccine type, age, gender, or other still unidentified characteristics (e.g., SES)? What is the consensus of care concerning COVID-19 vaccination in persons with autoimmune disorders and what evidence informs it? Our review will follow Arksey and O Malley s (2005) framework, enhanced by Levac et al. s team-based approach (2010), and adhering to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. To capture the broadest range of perspectives on the phenomenon of interest, data will be synthesized through numerical summaries describing general characteristics of included studies and thematic analysis. Subgroup analysis of primary outcomes will be performed to compare findings according to 1) the previous existence of autoimmune disorder, 2) the presence of relevant co-morbidities, 3) vaccine type; and other relevant factors that we may encounter as the research proceeds. Significance - COVID-19 has triggered the largest vaccination campaign in history, targeting literally the global human community. Drug safety is a crucial aspect of any medical intervention, critical to a proper assessment of the balance of risks and benefits. Our investigation should yield information useful to improve medical and public health practice in multiple ways, including assisting in clinical decision-making, policy development, and ethical medical practice.

Visceral adipose macrophage content does not associate with body mass index or systemic inflammation in COVID-19: an autopsy study (preprint)

Introduction: Adiposity, especially visceral adiposity with elevated body mass index (BMI), is associated with a hyperinflammatory syndrome and poor outcomes in patients with COVID-19. In other diseases such as obesity, type 2 diabetes, and rheumatoid arthritis, systemic inflammation is driven directly by visceral adipose macrophages which release pro-inflammatory cytokines. Currently it is unknown whether visceral adipose tissue macrophage content may similarly explain the observation that COVID-19 patients with elevated BMI are at risk for a hyperinflammatory syndrome and death. Methods: This was a retrospective study of hospitalized adults who died of COVID-19 between March 2020 and June 2020 and underwent autopsy. Visceral adipose tissue macrophage content was quantified by histological staining of visceral adipose tissue samples with CD68, using pericolic fat gathered at autopsy from each subject. Clinical data including inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive Protein (CRP), Troponin, D-dimer, Interleukin-6 (IL-6), and ferritin as well as BMI were collected from electronic medical records. Results: A total of 39 subjects were included in this study. There was no association between BMI and visceral adipose tissue macrophage content (Spearman R=0.025, p=0.88). Additionally, there was no association between adipose tissue macrophage content and any of the systemic markers of inflammation measured including ESR, CRP, Troponin, D-dimer, IL-6, and Ferritin (p>0.05 for all markers). Conclusion: Unlike chronic diseases such as obesity, type 2 diabetes, and rheumatoid arthritis, elevated BMI is not associated with increased visceral adipose tissue macrophage content in patients who died of COVID-19. Additionally, among patients who died of COVID-19, visceral adipose tissue macrophage content is not associated with markers of systemic inflammation. These results suggest that the elevations in systemic markers of inflammation-and the hyperinflammatory syndrome often observed during acute COVID-19-does not directly originate from visceral adipose macrophages as it seems to in chronic disease states.

Mapping current status and emerging trends in NETosis: A bibliometric study.

BACKGROUND: NETosis is a critical innate immune mechanism of neutrophils that contributes to the accelerated progression of autoimmune diseases, thrombosis, cancer, and coronavirus disease 2019 (COVID-19). This study qualitatively and quantitatively analyzed the relevant literature by bibliometric methods in order to provide a more comprehensive and objective view of the knowledge dynamics in the field. METHODS: The literature on NETosis was downloaded from the Web of Science Core Collection, analyzed with VOSviewer, CiteSpace, and Microsoft for co-authorship, co-occurrence, and co-citation analysis. RESULTS: In the field of NETosis, the United States was the most influential countries. Harvard University was the most active institutions. Mariana J. Kaplan and Brinkmann V were, respectively, the most prolific and most co-cited authors. Frontiers in Immunology, Journal of Immunology, Plos One, Blood, Science, Journal of Cell Biology, and Nature Medicine were the most influential journals. The top 15 keywords are associated with immunological and NETosis formation mechanisms. The keywords with the strongest burst detection were mainly related to COVID-19 (coronavirus, ACE2, SARS coronavirus, cytokine storm, pneumonia, neutrophil to lymphocyte ratio), and cancer (circulating tumor cell). CONCLUSION: Research on NETosis is currently booming. The mechanism of NETosis and its role in innate immunity, autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis, and thrombosis are the focus of research in the field of NETosis. A future study will concentrate on the function of NETosis in COVID-19 and recurrent metastasis of cancer.

Low-dose radiation therapy suppresses viral pneumonia by enhancing broad-spectrum anti-inflammatory responses via transforming growth factor-ß production.

Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-ß (TGF-ß) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-ß reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-ß production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-ß may be an alternative therapy for viral pneumonia.

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review.

BACKGROUND AND OBJECTIVES: Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata. METHODS: The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023. RESULTS: In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3). CONCLUSIONS: The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased.

Immunogenicity and safety of mixed COVID-19 vaccine regimens in patients with immune-mediated inflammatory diseases: a single-centre prospective cohort study.

OBJECTIVE: Among persons with immune-mediated inflammatory diseases (IMIDs) who received SARS-CoV-2 vaccines, we compared postvaccine antibody responses and IMID disease activity/states. DESIGN: Single-centre prospective cohort study. SETTING: Specialty ambulatory clinics in central Canada. PARTICIPANTS: People with inflammatory arthritis (n=78; 77% rheumatoid arthritis), systemic autoimmune rheumatic diseases (n=84; 57% lupus), inflammatory bowel disease (n=93; 43% Crohn's) and multiple sclerosis (n=72; 71% relapsing-remitting) (female 79.4%, white 84.7%, mean (SD) age 56.0 (14.3) years) received COVID-19 vaccinations between March 2021 and September 2022. PRIMARY OUTCOME: Postvaccination anti-spike, anti-receptor binding domain (anti-RBD) and anti-nucleocapsid (anti-NC) IgG antibodies tested by multiplex immunoassays compared across vaccine regimens and with responses in 370 age-matched and sex-matched vaccinated controls. SECONDARY OUTCOMES: COVID-19 infection and self-reported IMID disease activity/state. RESULTS: Most (216/327, 66.1%) received homologous messenger RNA (mRNA) (BNT162b2 or mRNA1273) vaccines, 2.4% received homologous ChAdOx1 and 30.6% received heterologous vaccines (23.9% ChAdOx1/mRNA, 6.4% heterologous mRNA) for their first two vaccines (V1, V2). Seroconversion rates were 52.0% (91/175) for post-V1 anti-spike and 58.9% (103/175) for anti-RBD; 91.5% (214/234) for post-V2 anti-spike and 90.2% (211/234) for anti-RBD; and were lower than controls (post-V2 anti-spike 98.1% (360/370), p<0.0001). Antibody titres decreased 3 months after V2 but increased 1 month after the third vaccine (V3) and 1 month after the fourth vaccine (V4) (BAU/mL median (IQR), anti-spike 1835 (2448) 1 month post-V2, 629.1 (883.4) 3 months post-V2, 4757.5 (7033.1) 1 month post-V3 and 4356.0 (9393.4) 1 month post-V4; anti-RBD 1686.8 (2199.44) 1 month post-V2, 555.8 (809.3) 3 months post-V2, 4280.3 (6380.6) 1 month post-V3 and 4792.2 (11 673.78) 1 month post-V4). If primed with a vector vaccine, an mRNA vaccine increased antibody titres to those comparable to homologous mRNA vaccines. Anti-RBD and anti-spike titres were higher in anti-NC seropositive (n=31; 25 participants) versus seronegative samples (BAU/mL median (IQR) anti-RBD 11 755.3 (20 373.1) vs 1248.0 (53 278.7); anti-spike 11 254.4 (15 352.6) vs 1313.1 (3106.6); both p<0.001). IMID disease activity/state and rates of self-reported moderate or severe IMID flare were similar across vaccinations. CONCLUSION: Heterologous COVID-19 vaccination improves seroconversion rates following a vector vaccine and does not lead to IMID disease flare. IMIDs benefit from at least three vaccines.

Immunogenicity of COVID-19 vaccines in adult patients with autoimmune inflammatory rheumatic diseases: A systematic review and meta-analysis.

COVID-19 vaccines approved by the Food and Drug Administration have been studied mainly in healthy individuals and there is limited information on their immunogenicity in patients with autoimmune diseases. Therefore, the current systematic review and meta-analysis study, aimed to comprehensively investigate the immunogenicity of these vaccines in patients with autoimmune inflammatory rheumatoid diseases (AIRDs). A comprehensive literature search was performed on various databases, including Google Scholar, PubMed, Web of Science, EMBASE, and Cochrane Library, to select cohort and randomized clinical trial (RCT) studies up to January 2022. Also, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist protocol and the I2 statistic were used for quality assessment and heterogeneity tests of the selected studies. Fixed and random-effects models were estimated based on the heterogeneity tests, and pooled data were determined as the ratio of mean (ROM) with a 95% confidence interval (CI). As a result, we found that vaccines can cause favorable immunogenicity and antibody response in vaccinated AIRD patients; however, older age and the concomitant consumption of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) could significantly reduce the vaccine immunogenicity. Consequently, our findings revealed significant humoral responses (seropositive) in AIRD patients following the administration of COVID-19 vaccines.

Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis.

Background: To investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA). Methods: Serological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains. Results: We prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken ("sampling interval") was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055). Conclusion: Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.

A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation.

Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because these molecules are redundant and pleiotropic. Here we review a novel therapeutic approach based on the use of the HSP60-derived Altered Peptide Ligand (APL) designed for RA and repositioned for the treatment of COVID-19 patients with hyperinflammation. HSP60 is a molecular chaperone found in all cells. It is involved in a wide diversity of cellular events including protein folding and trafficking. HSP60 concentration increases during cellular stress, for example inflammation. This protein has a dual role in immunity. Some HSP60-derived soluble epitopes induce inflammation, while others are immunoregulatory. Our HSP60-derived APL decreases the concentration of cytokines and induces the increase of FOXP3+ regulatory T cells (Treg) in various experimental systems. Furthermore, it decreases several cytokines and soluble mediators that are raised in RA, as well as decreases the excessive inflammatory response induced by SARS-CoV-2. This approach can be extended to other inflammatory diseases.

Self-evidence-based digital care programme improves health-related quality of life in adults with a variety of autoimmune diseases and long COVID: a retrospective study.

OBJECTIVE: To retrospectively investigate the feasibility and impact on health-related quality of life (HRQoL) of a digital care programme (DCP) designed to guide personalised diet and integrative interventions in a variety of autoimmune diseases and long COVID. METHODS: Adults who participated in the DCP between April 2020 and June 2022, and for whom baseline (BL) and end-of-programme (EOP) Patient-Reported Outcomes Measurement Information System (PROMIS) scores were available, were included in this retrospective study. Changes from BL to EOP were calculated using standardised T-scores. RESULTS: Two hundred two adults between 17 and 82 years old were included. Diagnoses included: rheumatoid arthritis (20.1%); long COVID (14.9%); psoriatic arthritis (10.9%); psoriasis (8.9%); systemic lupus erythematosus (6.4%); inflammatory bowel disease (5.9%); multiple sclerosis (5.9%); ankylosing spondylitis (5.4%) and other (23.3%). On average, individuals entered observations 7.6 times/day on 86% of programme days, attended 14 coach sessions and completed the programme in an average of 17.2 weeks. Statistically significant improvements were seen in all 10 PROMIS domains analysed. Individuals with higher severity of compromise at BL experienced greater average improvements than all-comers in all 10 PROMIS domains included. CONCLUSION: An evidence-based DCP that uses patient data to help identify hidden symptom triggers and guide personalised dietary and other non-pharmacological interventions was associated with a high level of engagement and adherence and statistically significant, clinically meaningful improvements in HRQoL. Those with the least favourable PROMIS scores at BL experienced the greatest improvements.

The COVID-19 epidemic curve and vaccine acceptance among patients with rheumatic diseases: an ecological study.

The attitudes toward emerging COVID-19 vaccines have been of great interest worldwide, especially among vulnerable populations such as patients with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to analyze the relationship between the nationwide number of COVID-19 cases and deaths, and vaccine acceptance or hesitancy of patients with RMDs from four patient care centers in Mexico. Furthermore, we explored differences in acceptance according to specific diagnoses: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This ecological study was a secondary analysis of a cross-sectional study using a validated questionnaire to measure vaccine acceptance. We generated a global Likert scale to evaluate overall attitudes toward the COVID-19 vaccine. We analyzed data from 1336 patients from March to September 2021: 85.13% (1169) were women, with a mean age of 47.87 (SD 14.14) years. The most frequent diagnoses were RA (42.85%, 559) and SLE (27.08%, 393). 635(47.52%) patients were unvaccinated, 253(18.93%) had one dose and 478(35.77%) had two doses. Of all participating patients, 94% were accepting toward the COVID-19 vaccine. Vaccine acceptance remained consistently high throughout the study. However, differences in vaccine acceptance are identified when comparing diagnoses. The peak of the national epidemic curve coincided with an increase in hesitancy among patients with RA. Contrastingly, patients with SLE became more accepting as the epidemic curve peaked. Mexican patients show high acceptance of the COVID-19 vaccine, influenced in part by a patient's specific diagnosis. Furthermore, vaccine acceptance increased mirroring the curve of COVID-19 cases and deaths in the country. This should be taken into consideration when updating recommendations for clinical practice.