Fourth Dose of BNT162b2 Vaccine for Patients with Autoimmune Rheumatic Diseases in a Nationwide Setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion of the B.1.1.529 (Omicron) variant and diminished antibody titers over time. We aim to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARD). METHODS: A retrospective analysis included ARD patients 18 years or older in the Clalit health management organization in Israel, insured 52% of the entire population, from January 16, 2022, to March 31, 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who received three doses of the BNT162b2 vaccine (control) to those who received the fourth dose. The primary outcome was COVID-19 infection, which was analyzed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and death. RESULTS: We included 43,748 ARD patients, of whom 27,766 and 15,982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6,942 (25.0%) of the control group and 1,754 (11.0%) of the fourth dose group (p < 0.001). Patients vaccinated with the fourth dose had a lower risk for COVID-19 infection in the entire cohort (HR 0.54, 95% CI 0.52-0.58) and throughout every subgroup regardless of the baseline characteristic or medical treatment except for rituximab. A similar association was observed in COVID-19-related hospitalization (HR 0.36, 95% C.I 0.22-0.61) and COVID-19-related death (HR 0.41, 95% C.I 0.24-0.71). CONCLUSION: Fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared to three doses among patients with no history of COVID-19 infection.

SARS-CoV-2 infection among patients with autoimmune rheumatic diseases; comparison between the Delta and Omicron waves in Israel.

OBJECTIVE: The Omicron variant of the coronavirus SARS-CoV-2 (COVID-19) had milder clinical impacts than prior variants. This study aimed to describe the impact of COVID-19 on Autoimmune Rheumatic Disease (ARD) patients during the Delta and Omicron variants waves. METHODS: We used data from Clalit Health Services (CHS), the largest health service in Israel. ARD patients diagnosed with COVID-19 between July 1, 2021, to December 1, 2021, were included in the Delta group. Patients diagnosed between December 2, 2021, to March 31, 2022, were included in the Omicron group based on the predominance of COVID-19 in Israel. The study outcomes were COVID-19-related hospitalization or death. RESULTS: The final study cohort included 8443 actively treated ARD patients diagnosed with COVID-19. 1204 patients were positive during the predefined Delta variant period, and 7249 were positive during the predefined Omicron variant period). Compared to the Delta group, the Omicron group showed a lower rate of COVID-19-related hospitalization (3.9% vs. 1.3% for the Delta Vs. Omicron accordingly, p<0.001) and COVID-19-related death (3.2% vs. 1.1% for the Delta Vs. Omicron accordingly, p<0.001). After applying multivariable regression models, the Omicron group showed a lower risk for COVID-19-related hospitalization (Relative risk 0.4, 95% CI 0.27-0.59) and COVID-19-related mortality (RR 0.48, 95% CI 0.31-0.75). CONCLUSION: ARD patients infected with the COVID-19 Omicron variant had a lower risk of developing COVID-19-related adverse outcomes compared to the Delta variant.

SARS-CoV-2 infection among patients with autoimmune rheumatic diseases' comparison between the Delta and Omicron waves in Israel

<h4>Objective</h4> The Omicron variant of the coronavirus SARS-CoV-2 (COVID-19) had milder clinical impacts than prior variants. This study aimed to describe the impact of COVID-19 on Autoimmune Rheumatic Disease (ARD) patients during the Delta and Omicron variants waves. <h4>Methods</h4> We used data from Clalit Health Services (CHS), the largest health service in Israel. ARD patients diagnosed with COVID-19 between July 1, 2021, to December 1, 2021, were included in the Delta group. Patients diagnosed between December 2, 2021, to March 31, 2022, were included in the Omicron group based on the predominance of COVID-19 in Israel. The study outcomes were COVID-19-related hospitalization or death. <h4>Results</h4> The final study cohort included 8443 actively treated ARD patients diagnosed with COVID-19. 1204 patients were positive during the predefined Delta variant period, and 7249 were positive during the predefined Omicron variant period). Compared to the Delta group, the Omicron group showed a lower rate of COVID-19-related hospitalization (3.9% vs. 1.3% for the Delta Vs. Omicron accordingly, p<0.001) and COVID-19-related death (3.2% vs. 1.1% for the Delta Vs. Omicron accordingly, p<0.001). After applying multivariable regression models, the Omicron group showed a lower risk for COVID-19-related hospitalization (Relative risk 0.4, 95% CI 0.27-0.59) and COVID-19-related mortality (RR 0.48, 95% CI 0.31-0.75). <h4>Conclusion</h4> ARD patients infected with the COVID-19 Omicron variant had a lower risk of developing COVID-19-related adverse outcomes compared to the Delta variant.

Perceived Stress, Resilience, and Wellbeing in Seasoned Isha Yoga Practitioners Compared to Matched Controls During the COVID-19 Pandemic.

Background: Yoga practices, including breathing, meditation, and posture protocols (asanas), have been shown to facilitate physical and mental wellbeing. Methods: Seasoned yoga practitioners were recruited from the Isha Foundation. Recruitment of the comparison group was achieved using snowball sampling and were not yoga practitioners. Participants in the non-yoga group were randomized to a 3-min Isha practice or a comparator group asked to perform 15-min of daily reading. Participants completed a series of web-based surveys (REDCap) at baseline, 6, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess for: perceived stress (PSS), mood states [anxiety and depression (PHQ-4), joy (DPES-Joy subscale)], mindfulness attention and awareness (MAAS), resilience (BRS), mental wellbeing (WEMWBS) and recovery from traumatic event (PTGI). Weekly activity diaries were employed as a tool for collecting compliance information from study participants. Perceived stress scale scores were identified as primary outcome for this study. Findings: The median Perceived Stress Scale (PSS) score for the yoga practitioners compared to the active and placebo comparators was significantly lower at all time-points: baseline: 11 [IQR 7-15] vs. 16 [IQR 12-21] in both the active and placebo comparators (p < 0.0001); 6 weeks: 9 [IQR 6-13] vs. 12 [IQR 8-17] in the active comparator and 14 [IQR 9-18] in the placebo comparator (p < 0.0001); and 12 weeks: 9 [IQR 5-13] vs. 11.5 [IQR 8-16] in the active comparators and 13 [IQR 8-17] in the placebo comparator (p < 0.0001). Among the randomized participants that were compliant for the full 12 weeks, the active comparators had significantly lower median PSS scores than the placebo comparators 12 weeks [10 (IQR 5-14) vs. 13 (IQR 8-17), p = 0.017]. Further, yoga practitioners had significantly lower anxiety at all three-time points (p < 0.0001), lower depression at baseline and 6 weeks (p < 0.0003), and significantly higher wellbeing (p < 0.0001) and joy (p < 0.0001) at all three-time points, compared to the active and placebo comparator groups. Interpretation: The lower levels of stress, anxiety, depression, and higher level of wellbeing and joy seen in the yoga practitioners compared to the active and placebo comparators illustrate the impact of regular yoga practices on mental health even during the pandemic. Trial Registration: ClinicalTrials.gov, identifier: NCT04498442.

Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. METHODS: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. RESULTS: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP. CONCLUSION: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. IMPLICATION STATEMENT: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

Short Term Effects of Inner Engineering Completion Online Program on Stress and Well-Being Measures.

Introduction: The Covid-19 pandemic has been a major disruptor of routine life, resulting in increased stress and predisposing people to negative outcomes, such as insomnia, anxiety and hopelessness. Mind-body interventions have improved concentration, emotional balance, and positive emotions, with an enhanced sense of productivity, and self-confidence. We therefore hypothesized that exposure to an online mind-body intervention, "Inner Engineering Completion Online (IECO)," would reduce stress and promote well-being. Methods: This prospective cohort study enrolled participants registered for the IECO courses, which for the first time were delivered remotely, online. Participants learned a 21-min meditation practice called Shambhavi Mahamudra Kriya during the course, which incorporates controlled breathing and mediation techniques. Each enrolled participant was asked to complete self-reported electronic surveys at three key time points: at the time of consent, immediately after completing IECO, and 6 weeks after IECO completion. Effects of IECO practice were assessed using four well-validated neuropsychological scales: Perceived Stress Scale (PSS), Positive Emotion/Relationship/Engagement Scale (PERMA) Profiler, Pittsburgh Sleep Quality Index (PSQI), and Mindful Attention Awareness Scale (MAAS). A Signed Rank test was used to analyze the survey data and P-values of < 0.05 were considered statistically significant. Results: Of the 375 participants interested in participation, 164 participants were eligible. Sixty-eight participants completed surveys at all time points and were identified as compliant participants. The baseline median score for PSS in compliant participants (n = 95) was 13.5 (IQR 9, 18); immediate post-IECO median PSS score was 12 (IQR 8, 16) demonstrating a 1.5 unit decrease in PSS scores (p-value = 0.0023). Similarly, comparing PSS scores in compliant participants (n = 68) for immediate Post IECO [11.5 (IQR 8, 15.5)] to PSS scores at six weeks [8 (IQR 4.5, 12.5)] showed a statistically significant 3.5-unit decrease, indicating a reduction in stress upon routine practice of the intervention (p < 0.0001). Conclusion: Incorporating the remotely delivered mind-body intervention Shambhavi Mahamudra Kriya into daily life via the IECO program over as few as 6 weeks produced a significant stress reduction, improvement in sleep quality and mindfulness. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04189146].

BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study.

INTRODUCTION: Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited. METHODS: We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome. RESULTS: We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy. CONCLUSION: Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.