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Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy., (© 2024. The Author(s).)

Objectives: We aimed to investigate the gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing the data obtained through the international COVID-19 vaccination in autoimmune disease e-survey., Methods: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVID-19 vaccination in autoimmune disease database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of the substantial differences in outcomes., Results: A total of 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [interquartile range], P < .001) and were more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, P < .001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [interquartile range], P = .004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed that women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue., Conclusions: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Background: Implementation of remote monitoring solutions and digital alerting tools in health care has historically been challenging, despite the impetus provided by the COVID-19 pandemic. To date, a health systems-based approach to systematically describe barriers and facilitators across multiple domains has not been undertaken., Objective: We aimed to undertake a comprehensive mixed methods analysis of barriers and facilitators for successful implementation of remote monitoring and digital alerting tools in complex health organizations., Methods: A mixed methods approach using a modified Technology Acceptance Model questionnaire and semistructured interviews mapped to the validated fit among humans, organizations, and technology (HOT-fit) framework was undertaken. Likert frequency responses and deductive thematic analyses were performed., Results: A total of 11 participants responded to the questionnaire and 18 participants to the interviews. Key barriers and facilitators could be mapped onto 6 dimensions, which incorporated aspects of digitization: system use (human), user satisfaction (human), environment (organization), structure (organization), information and service quality (technology), and system quality (technology)., Conclusions: The recommendations proposed can enhance the potential for future remote sensing solutions to be more successfully integrated in health care practice, resulting in more successful use of "virtual wards.", Trial Registration: ClinicalTrials.gov NCT05321004; https://www.clinicaltrials.gov/study/NCT05321004., (©Fahad Mujtaba Iqbal, Ravi Aggarwal, Meera Joshi, Dominic King, Guy Martin, Sadia Khan, Mike Wright, Hutan Ashrafian, Ara Darzi. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 06.05.2024.)

Objectives: We investigated coronavirus disease 2019 (COVID-19) vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study., Methods: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares and AID-related treatment modifications were analysed upon diagnosis of AID vs healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine., Results: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, P = 0.01; minor AE 40% vs 25.9%, P = 0.03; major AE 17.5% vs 4.6%, P < 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination disease flares were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a disease flare were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively., Conclusion: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and for the fetus by passive immunization appear to outweigh potential risks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination., Methods: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio., Results: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs., Conclusion: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination., (© 2024 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy., Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown., Methods: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs)., Discussion: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them., Conclusion: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them., (© 2024 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs)., Methods: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models., Results: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares., Conclusion: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Secondary bacterial infections during COVID-19 hospitalization have been reported in about 6-15% of patients., Aims: To study the secondary bacterial infections that affected the COVID-19 patients during their hospitalisation and to unearth the bacteriological profile of samples obtained after their demise., Settings and Design: This prospective study was carried out at a COVID-19 dedicated, apex tertiary care centre in North India from July 2020 to April 2021., Methods and Materials: Samples of 268 patients were considered for the study. Nasopharyngeal swab specimen, blood, and tissue (lung) were collected from the deceased body as early as possible and processed., Statistical Analysis: Statistical analyses were performed using STATA version 11.1 (Stata Corp., College Station, TX, USA)., Results: A total of 170 samples were received from patients before their death, which included blood, urine, respiratory samples, pus, and cerebrospinal fluid. Forty-four pathogens were isolated, which consisted of Acinetobacter baumannii (43.1%), Klebsiella pneumoniae (36.3%), Escherichia coli (11.3%), and Pseudomonas aeruginosa (4.5%), Enterococcus faecium (4.5%). Two hundred fifty-eight samples were collected from the deceased bodies wherein the nasopharyngeal sample was highest, followed by tissue and blood. A total of 43 pathogens were isolated among them which included A. baumannii (44.1%), followed by K. pneumoniae (25.5%), E. coli (20.9%), P. aeruginosa (6.97%) and Enterobacter cloacae (2.3%). All these isolates were highly resistant to antimicrobials., Conclusions: In our study, bacterial profiles in antemortem and postmortem samples were found to be similar, suggesting that resistant pathogens may be the cause of mortality in COVID-19 infected hospitalised patients.

To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases., (© 2023. The Author(s).)

This study aimed to assess the incidence, predictors, and outcomes of breakthrough infection (BI) following coronavirus disease (COVID-19) vaccination in patients with systemic sclerosis (SSc), a risk group associated with an immune-suppressed state and high cardiopulmonary disease burden. Cross-sectional data from fully vaccinated respondents with SSc, non-SSc autoimmune rheumatic diseases (AIRDs), and healthy controls (HCs) were extracted from the COVAD database, an international self-reported online survey. BI was defined according to the Centre for Disease Control definition. Infection-free survival was compared between the groups using Kaplan-Meier curves with log-rank tests. Cox proportional regression was used to assess the association between BI and age, sex, ethnicity, and immunosuppressive drugs at the time of vaccination. The severity of BI in terms of hospitalization and requirement for oxygen supplementation was compared between groups. Of 10,900 respondents, 6836 fulfilled the following inclusion criteria: 427 SSc, 2934 other AIRDs, and 3475 HCs. BI were reported in 6.3% of SSc, 6.9% of non-SSc AIRD, and 16.1% of HCs during a median follow-up of 100 (IQR: 60-137) days. SSc had a lower risk for BI than HC [hazard ratio (HR): 0.56 (95% CI 0.46-0.74)]. BIs were associated with age [HR: 0.98 (0.97-0.98)] but not ethnicity or immunosuppressive drugs at the time of vaccination. Patients with SSc were more likely to have asymptomatic COVID-19, but symptomatic patients reported more breathlessness. Hospitalization [SSc: 4 (14.8%), HCs: 37 (6.6%), non-SSc AIRDs: 32(15.8%)] and the need for oxygenation [SSc: 1 (25%); HC: 17 (45.9%); non-SSc AIRD: 13 (40.6%)] were similar between the groups. The incidence of BI in SSc was lower than that in HCs but comparable to that in non-SSc AIRDs. The severity of BI did not differ between the groups. Advancing age, but not ethnicity or immunosuppressive medication use, was associated with BIs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims/introduction: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients., Materials and Methods: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out., Results: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients)., Conclusions: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys., Methods: The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs., Results: Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a-d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001).In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective.A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001)., Conclusion: Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys., Methods: The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups., Results: We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs - OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs - OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7-10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8-0.97)]., Conclusion: Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Objectives: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study., Methods: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI)., Results: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not., Interpretation Conclusions: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death., (Copyright © 2023 Copyright: © 2023 Indian Journal of Medical Research.)

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life., (© 2023. The Author(s).)

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb-June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35-58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2-7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period., (© 2023. The Author(s).)

Objective: To determine COVID-19 vaccine-related adverse events (AEs) in the seven-day post-vaccination period in patients with SLE vs autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HC)., Methods: Data were captured through the COVID-19 Vaccination in Autoimmune Diseases (COVAD) questionnaire (March-December 2021). Multivariable regression models accounted for age, gender, ethnicity, vaccine type and background treatment., Results: Among 9462 complete respondents, 583 (6.2%) were SLE patients (mean age: 40.1 years; 94.5% females; 40.5% Asian; 42.9% Pfizer-recipients). Minor AEs were reported by 83.0% of SLE patients, major by 2.6%, hospitalization by 0.2%. AE and hospitalization frequencies were similar between patients with active and inactive SLE. Rashes were more frequent in SLE patients vs HC (OR; 95% CI: 1.2; 1.0, 1.5), chills less frequent in SLE vs AIRDs (0.6; 0.4, 0.8) and nrAIDs (0.5; 0.3, 0.8), and fatigue less frequent in SLE vs nrAIDs (0.6; 0.4, 0.9). Pfizer-recipients reported higher overall AE (2.2; 1.1, 4.2) and injection site pain (2.9; 1.6, 5.0) frequencies than recipients of other vaccines, Oxford/AstraZeneca-recipients more body ache, fever, chills (OR: 2.5, 3.0), Moderna-recipients more body ache, fever, chills, rashes (OR: 2.6, 4.3). Hospitalization frequencies were similar across vaccine types. AE frequencies were similar across treatment groups, although chills were less frequent in antimalarial users vs non-users (0.5; 0.3, 0.9)., Conclusion: While COVID-19 vaccination-related AEs were reported by four-fifths of SLE patients, those were mostly minor and comparable to AEs reported by healthy individuals, providing reassurance regarding COVID-19 vaccination safety in SLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients., Methods: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed., Results: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies., Conclusion: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The safety profile of COVID-19 vaccines is understudied in patients with systemic sclerosis (SSc). We compared short-term adverse events (AEs) 7 days following vaccination in patients with SSc vs other rheumatic (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). The COVID-19 Vaccination in autoimmune diseases (COVAD) self-reporting e-survey was circulated by a group of > 110 collaborators in 94 countries from March to December 2021. AEs were analyzed between different groups using regression models. Of 10,679 complete respondents [73.8% females, mean age 43 years, 53% Caucasians], 478 had SSc. 83% had completed two vaccine doses, Pfizer-BioNTech (BNT162b2) (51%) was the most common. Minor and major AEs were reported by 81.2% and 3.3% SSc patients, respectively, and did not differ significantly with disease activity or different vaccine types, though with minor symptom differences. Frequencies of AEs were not affected by background immunosuppression, though SSc patients receiving hydroxychloroquine experienced fatigue less commonly (OR 0.4; 95% CI 0.2-0.8). Frequency of AEs and hospitalisations were similar to other AIRDs, nrAIDs, and HC except a higher risk of chills (OR 1.3; 95% CI 1.0-1.7) and fatigue (OR 1.3; 95% CI 1.0-1.6) compared to other AIRDs. COVID-19 vaccines were largely safe and well tolerated in SSc patients in the short term. Background immunosuppression and disease activity did not influence the vaccination-related short-term AEs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives. The goal of this study is to describe placental pathology after infection with SARS-CoV-2 before the predominance of variants of concern (pre-VOC) and during eras of predominant transmission of the Alpha & Gamma (co-circulating), Delta, and Omicron variants. Methods. We used county-level variant data to establish population-level variant proportions, SARS-CoV-2 PCR to identify cases, and IgG serology to exclude latent infections from controls and histopathologic examination to identify placental pathology. Results. We report findings in 870 placentas from pregnancies complicated by SARS-CoV-2 including 90 with infection in the Alpha/Gamma era, 60 from the Delta era and 56 from the Omicron era. Features of maternal vascular malperfusion (MVM), including decidual arteriopathy, were significantly more frequent after SARS-CoV-2 infection. The risk of these findings varied over time, with the highest rates in the Delta era. Increased COVID-19 severity and the presence of comorbidities strengthened these associations. Conclusion. MVM is a feature of SARS-CoV-2 infection in pregnancy. Lesion frequency changed with the predominant circulating virus and should be considered with new variants.

Objective: To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms., Design: Prospective, open-label, multicentre, stratified, randomised clinical trial., Setting: Five hospitals in UK and India, from September 2020 to May 2021., Participants: Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset., Intervention: Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care., Primary Outcomes: The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days., Results: Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047)., Conclusion: Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients., Trial Registration Numbers: EudraCT Number: 2020-002952-18, NCT05007678., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs)., Methods: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores., Results: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios., Conclusion: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status., (© 2023 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Objectives: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs., Methods: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease., Results: A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis., Conclusion: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs)., Methods: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis., Results: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7)., Conclusions: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs., (© 2022. The Author(s).)

Objectives: COVID-19 vaccines have been proven to be safe in the healthy population. However, gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). COVID-19 vaccination-related adverse events (AEs) in patients with SAIDs and healthy controls (HC) seven days post-vaccination were assessed in the COVAD study, a patient self-reported cross-sectional survey., Methods: The survey was circulated in early 2021 by >110 collaborators (94 countries) to collect SAID details, COVID-19 vaccination details and 7-day vaccine AEs, irrespective of respondent vaccination status. Analysis was performed based on data distribution and variable type., Results: Ten thousand nine hundred respondents [median (interquartile range) age 42 (30-55) years, 74% females and 45% Caucasians] were analysed; 5867 patients (54%) with SAIDs were compared with 5033 HCs. Seventy-nine percent had minor and only 3% had major vaccine AEs requiring urgent medical attention (but not hospital admission) overall. Headache [SAIDs = 26%, HCs = 24%; odds ratio (OR) = 1.1 (95% CI: 1.03, 1.3); P = 0.014], abdominal pain [SAIDs = 2.6%, HCs = 1.4%; OR = 1.5 (95% CI: 1.1, 2.3); P = 0.011], and dizziness [SAIDs = 6%, HCs = 4%; OR = 1.3 (95% CI: 1.07, 1.6); P = 0.011], were slightly more frequent in SAIDs. Overall, major AEs [SAIDs = 4%, HCs = 2%; OR = 1.9 (95% CI: 1.6, 2.2); P < 0.001] and, specifically, throat closure [SAIDs = 0.5%, HCs = 0.3%; OR = 5.7 (95% CI: 2.9, 11); P = 0.010] were more frequent in SAIDs though absolute risk was small (0-4%). Major AEs and hospitalizations (<2%) were comparable across vaccine types in SAIDs., Conclusion: Vaccination against COVID-19 is safe in SAID patients. SAIDs were at a higher risk of major AEs than HCs, though absolute risk was small. There are small differences in minor AEs between vaccine types in SAID patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups., (© 2022. The Author(s).)

Introduction/aims: In this study we investigated COVID-19 vaccination-related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs)., Methods: Seven-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics were obtained and multivariable regression was performed., Results: Ten thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30-455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04-7.3) and minor (OR, 1.5; IQR, 1.1-2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2-4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1-3.3; and OR, 2.2; IQR, 1.1-4.3, respectively). Overall, ADEs were less frequent in inclusion-body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients., Discussion: Seven-day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs. Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Patients with rheumatic diseases (RDs) like DM are known to be vulnerable towards various types of infections due to aggressive disease activity mandating high dose immunosuppressive therapy. The severity of COVID-19 in RDs is limited in literature due to the heterogeneous nature of the condition. Therefore, specific details on mortality is essential to navigate any precautions required in the treatment., Objectives: To determine outcomes of COVID-19 in DM as compared to controls, and identify the risk association of gender, race, interstitial lung disease, neoplasms, and use of immunosuppressant., Methods: Retrospective data of individuals with DM and COVID-19 and the general population with COVID-19 between January 2020 to August 2021 was retrieved from the TriNetX database. 1:1 Propensity Score matching was used to adjust for confounders. We assessed COVID-19 outcomes such as mortality, hospitalisation, ICU admission, severe COVID-19, mechanical ventilation (MV), acute kidney injury (AKI), venous thromboembolism (VTE), ischemic stroke, acute respiratory distress syndrome (ARDS), renal replacement therapy (RRT) and sepsis. Subgroup analyses included gender, race, ILD, cancer patients, disease-modifying rheumatic drugs (DMARDs) use, and glucocorticoids (GC) use., Results: We identified 5,574 DM patients with COVID-19, and 5,574 general population with COVID-19 (controls). DM with COVID-19 had a lower risk of mortality in comparison to controls [RR 0.76], hospitalisation [RR 0.8], severe COVID-19 [RR 0.76], AKI [RR 0.83], and sepsis [RR 0.73]. Males and African Americans were more likely to develop AKI [RR 1.35, 1.65], while African Americans had higher odds for severe COVID-19 [RR 1.62] and VTE [RR 1.54]. DM with ILD group also experienced higher odds for severe COVID-19 infection [RR 1.64], and VTE [RR 2.06]. DM patients receiving DMARDs and glucocorticoids had higher odds for hospitalisation [RR 1.46, 2.12], and sepsis [RR 3.25, 2.4] Subgroup analysis of 5-year neoplasm history amongst DM patients with COVID-19 was inadequate for meaningful comparison., Conclusion: Dermatomyositis patients without comorbities have reasonable COVID-19 outcomes including mortality and hospitalisation. Black race, male gender, ILD, DMARDS and glucocorticoid users, are associated with poor outcomes., Competing Interests: Declaration of Competing Interest SA has received honorarium as speaker for Pfizer, DrReddy's, Cipla and Novartis, has received an APLAR research grant, all unrelated to the current study, and has no other potential conflicts of interest. SK has received congress travel, accommodation, and participation fee support (12th Anatolian Rheumatology Days) from Abbvie. All other authors declare no competing interests relevant to the manuscript., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21 ); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75-85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195-197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646 ). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India., Methods: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model., Results: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM., Conclusions: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID., Competing Interests: The authors have declared that no competing interests exist.

Introduction: This study aimed at assessing the vaccine effectiveness (VE) of Covishield, which is identical to AstraZeneca vaccine, in preventing laboratory-confirmed Covid-19., Methods: Using test-negative case-control design, information on vaccination status of cases with Covid-19 among healthcare workers in our institution in Puducherry, India, and an equal number of controls matched for age and date of testing, was obtained. The groups were compared using multivariable conditional logistic regression to calculate odds ratios (OR). VE was calculated as 100*(1-adjusted odds ratio)%., Results: Using data from 360 case-control pairs, VE of one dose and of two doses, in providing protection against Covid-19 was 49% (95% CI: 17%-68%) and 54% (27%-71%), respectively. Among cases with moderately severe disease that required oxygen therapy, VE following any number of vaccine doses was 95% (44%-100%)., Conclusion: Covishield vaccine protected significantly against Covid-19, with a higher protection rate against severe forms of disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The Pfizer-BioNTech COVID-19 vaccine has been authorized by the U.S. Food and Drug Administration as it demonstrated 95% effectiveness against the SARS-CoV-2 virus. Although the initial vaccine trials showed a favorable side effect profile, there have been concerns regarding activation of aberrant immune responses, triggering autoimmunity. This is a case report of a 68-year-old woman without history of autoimmune conditions, who presented to our emergency department 7 days after receiving the Pfizer-BioNTech COVID-19 vaccine. Her initial symptoms were suggestive of polymyalgia rheumatica, and she had nearly complete response to steroids. Interestingly, she later met criteria for classified systemic lupus erythematous given the development of inflammatory arthritis, positive ANA, and positive dsDNA. The temporal relationship of her symptoms that started 2 days after vaccine administration could suggest a possible association between the Pfizer-BioNTech COVID-19 and the development of systemic lupus erythematous., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Children with cystic fibrosis (CF) constitute a high-risk group for COVID-19 with underlying chronic lung disease. COVID-19 severity varying from mild infection to need of intensive care has been described in children with CF. Two children with significant underlying pulmonary morbidity are described here, who developed severe disease following SARS-CoV-2 infection. Case 1 (a 9-y-old boy) had pneumonia with respiratory failure requiring noninvasive ventilation support. He had delayed clearance of SARS-CoV-2, with recurrence of symptomatic disease with short asymptomatic period in between. He was also diagnosed with CF-related diabetes and allergic bronchopulmonary aspergillosis during the second episode. Case 2 (an 18-mo-old boy) had two episodes of SARS-CoV-2-related severe lower respiratory infection within a period of 2 mo, requiring high-flow nasal oxygen support. Both children had 3 rd pulmonary exacerbation but SARS-CoV-2 was not detected in respiratory secretions. To conclude, children with CF with underlying pulmonary morbidity, can develop severe COVID-19 and prolonged SARS-CoV-2 shedding., (© 2022. Dr. K C Chaudhuri Foundation.)

Coronavirus Disease 2019 (COVID-19) is spreading across the world, and vaccinations are running parallel. Coronavirus has mutated into a triple-mutated virus, rendering it deadlier than before. It spreads quickly from person to person by contact and nasal or pharyngeal droplets. The COVID-19 database 'Our World in Data' was analyzed from February 24, 2020, to September 26, 2021, and predictions on the COVID positives and their mortality rate were made. Factors such as Vaccine data for the First and Second Dose vaccinated individuals and COVID positives that influence the fluctuations in the COVID-19 death ratio were investigated and linear regression analysis was performed. Based on vaccination doses (partial or complete vaccinated), models are created to estimate the number of patients who die from COVID infection. The estimation of variance in the datasets was investigated using Karl Pearson's coefficient. For COVID-19 cases and vaccination doses, a quartic polynomial regression model was also created. This predictor model helps to predict the number of deaths due to COVID-19 and determine the susceptibility to COVID-19 infection based on the number of vaccine doses received. SVM was used to analyze the efficacy of models generated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rustagi, Bajaj, Tanvi, Singh, Aggarwal, AlAjmi, Hussain, Hassan, Singh and Singh.)

Competing Interests: Declaration of interests All authors are members of WHO's Strategic Advisory Group of Experts on Immunization (SAGE). This paper synthesises data discussed by and contributed to by all authors and on which the views expressed are based. These views do not represent an official position or recommendation of SAGE or WHO. AJP has received grants from the Medical Research Council, the Bill & Melinda Gates Foundation, the European Commission, Gavi the Vaccine Alliance, and AstraZeneca to his university. He is chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation but does not participate in policy decisions on COVID-19 vaccines. He is a member of WHO's SAGE group and is an National Institute for Health Research senior investigator. He is chief investigator on COVID-19 vaccine clinical trials done by Oxford University, Oxford, UK, funded by National Institute for Health Research. KM and PBM serve on a data safety monitoring board for Novavax COVID-19 vaccines. HN serves on a data safety monitoring board for Oxford University on ComCov studies. She is secretary of the National Immunisation Technical Advisory Group of Finland, chair of the WHO SAGE COVID-19 working group, and vice chair of the WHO SAGE group. KMN receives grants from Pfizer and National Institutes of Health for involvement in COVID-19 vaccine trials. IJ has received grants to his institution from Coalition for Epidemic Preparedness Innovations and the Bill & Melinda Gates Foundation for studies related to COVID-19. SAM has received grants to his institution from Pfizer, Minervax, and GlaxoSmithKline for group B streptococcal vaccine studies, from the Bill & Melinda Gates Foundation for multiple studies, and from Novavax for a co-funded COVID-19 study. All other authors declare no competing interests.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators., (© 2021. Crown.)

Background: There is increased incidence of barotrauma in COVID-19 patients, probably due to disease pathology, oxygen therapy and coughing. We aimed to retrospectively compare the characteristics, associations and outcomes of COVID-19 patients with and without barotrauma in the intensive care unit (ICU)., Methods: All adults admitted between October 1st and December 31st 2020 in the ICUs of a COVID-19 hospital were retrospectively analysed for presence of a 'barotrauma event' (presence of at least one of pneumothorax, pneumomediastinum, subcutaneous emphysema or bronchopleural fistula). A control group was formed by matching each case to a patient belonging to the same gender and age range from the remaining patients in the cohort, i.e., those without barotrauma. Demographic details, ICU stay details, details of oxygen therapy and ventilation, and outcomes were noted and compared., Results: Of 827 patients, 30 patients (3.6%) developed barotrauma events. The typical patient was middle aged (median age 55.5 years) and male (73.3%). The mortality rate was significantly higher in the barotrauma group (83.3% vs. 43.3%, P < 0.001), and odds of survival decreased by 85% if barotrauma occurred (OR 0.15; 95% CI: 0.46-0.51). Patients who developed barotrauma spent a longer time on a high-flow nasal cannula (median 6.7 vs. 1.73 days, P = 0.04), and mechanical ventilation (median 9.54 vs. 0.867 days, P < 0.001), and had a longer ICU stay (median 15.5 vs. 9 days, P = 0.014). The most common event was pneumothorax (26/30)., Conclusions: Barotrauma in the COVID-19 ICU is associated with prolonged ICU stay, higher odds of mortality and longer duration spent on mechanical ventilation and a high-flow nasal cannula. Key words: barotrauma, ICU, COVID-19, mortality, pneumothorax.

The Novel Coronavirus which emerged in India on January/30/2020 has become a catastrophe to the country on the basis of health and economy. Due to rapid variations in the transmission of COVID-19, an accurate prediction to determine the long term effects is infeasible. This paper has introduced a nonlinear mathematical model to interpret the transmission dynamics of COVID-19 infection along with providing vaccination in the precedence. To minimize the level of infection and treatment burden, the optimal control strategies are carried out by using the Pontryagin's Maximum Principle. The data validation has been done by correlating the estimated number of infectives with the real data of India for the month of March/2021. Corresponding to the model, the basic reproduction number [Formula: see text] is introduced to understand the transmission dynamics of COVID-19. To justify the significance of parameters we determined the sensitivity analysis of [Formula: see text] using the parameters value. In the numerical simulations, we concluded that reducing [Formula: see text] below unity is not sufficient enough to eradicate the COVID-19 disease and thus, it is required to increase the vaccination rate and its efficacy by motivating individuals to take precautionary measures., (© 2021. The Author(s).)

Coronavirus disease (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is a positive single-stranded RNA virus having a large genome ~30 kb. SARSCoV- 2 is zoonotic and highly contagious, causing severe pneumonia-like symptoms. The efficacy of the different potential drug and drug candidates against COVID-19 has been investigated, which are under various stages of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated in the prevention and therapy of COVID-19. The plant produces secondary metabolites in response to viral infection. Different classes of secondary metabolites have different mechanisms to counter virus attacks. Many nanomaterials produced by carbohydrates and lipids have been exploited for their in-vitro and in-vivo delivery of antiviral therapeutics. The vaccine has shown impressive results in producing antibodies against SARS-CoV2 and has been evaluated for safety, tolerance, and preliminary immunogenicity. Similarly, DNA/RNA-based therapy has shown high clinical significance. Various forms of vitamins, minerals, herbs, and phytonutrients help to enhance immunity and be implicated in the control of COVID-19. However, such measures should not replace social distancing, quarantine and special care., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)