关键词： COVID-19   Phase 1b trial   Receptor-interacting protein 1   RIPK1   RIPK1 inhibitor   SIR1-365  

摘要： Background Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Methods This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy. Results Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were >= grade 3. Fewer SIR1-365-treated vs . placebo-treated patients experienced TEAEs (30.4% vs. 57.9%) and serious TEAEs (13.0% vs. 26.3%) within 28 days of the first dose. There were no serious treatment-related TEAEs or deaths. SIR1-365 vs . placebo significantly increased arterial oxygenation from baseline to day 7 (least-squares mean change [standard error]: 109.4 [26.4] vs. -24.2 [23.6]; P =0.0095), significantly reduced hospitalization duration after treatment (mean±standard deviation: [4.7±3.7] days vs . [8.6±5.6] days; P =0.0145) and respiratory failure incidence (8.3% vs . 38.1%; two-sided P =0.0291) during the study, and numerically shortened

摘要： The purpose of this study was to explore underlying patterns in the users’ discussions in an online community on the darker effects of COVID-19. Understanding these patterns is critical as they can provide new information in tailoring support to individuals facing specific post-pandemic issues. Two methods were used to identify patterns in large volumes of publicly available responses (n = 23,957 posts; ~ 1,061,825 words) from an online community. Qualitatively (using Gioia methodology), 1000 random responses were manually coded by two coders and vetted by an investigator. As it was difficult to manually code such a big dataset, a quantitative approach building a topic model was employed with a language model. Qualitative analyses revealed 20 themes, including mental health (13%), impacts of direct and indirect deaths on socio-economically vulnerable groups (e.g. children and elderly, 10.4%), increasing sociopolitical divide and vaccination debate (6.8%), and work-related issues (e.g. burnout and layoffs, 6%). Topic analyses resulted in similar categories (n = 30), including physical health, loss experiences during COVID-19 and suicide; sociopolitical impact and adaptations in pandemic lifestyle; mental health and vaccination; pandemic restrictions, youth and behavioral expectations; distrust for institutions and resource scarcity; staffing issues and personal crisis; disrupted careers; and childcare challenges and economic shifts. As researchers are harnessing vast amounts of real-time human interaction data to study a variety of public health issues, our study provides insights into the specific challenges that people experienced when it became convenient to share concerns online amid an overloaded healthcare system during the pandemic.

关键词： COVID-19 Vaccination   65 Years and Older   Older Adults   Inequality   Race   Ethnicity   Sex  

摘要： Background Age, race, ethnicity, and sex are important determinants of COVID-19 outcomes. Older adults (65 years and older) are at the highest risk of COVID-19 morbidity and mortality. Analyzing their vaccine uptake by subclassifying demographics is rare and can assist vaccination policies. This study investigates COVID-19 dose-one and two vaccine uptakes among them by race, ethnicity, and sex. Methods Immunization registry data was used to calculate temporal changes in older adults’ COVID-19 vaccine uptake by race, ethnicity, race-sex, and ethnicity-sex in Kentucky’s most populous county, Jefferson County, during the first six quarters of the COVID-19 vaccination program. Results By May 2022, the county’s Asian residents had the highest dose-one and two vaccination rates (97.0% and 80.4%), then White residents (90.0% and 80.2%). Black residents had one of the lowest COVID-19 vaccination rates (87.3% and 77.3%). The rate among Hispanic residents (82.0% and 66.4%) was considerably lower than non-Hispanic residents (90.2% and 80.1%). The rates were consistently lower in males. Conclusions Racial, ethnic, and sex-based COVID-19 vaccine inequalities were largely maintained during the study period. Vaccine rollout practices and promotional programs should aim to boost the uptake of the COVID-19 vaccination among racial minority and male older adults.

摘要： Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21–27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

摘要： The persistent symptoms arising from COVID-19 infection pose a substantial threat to patients’ health, carrying significant implications. Amidst the evolving COVID-19 control strategies in China, healthcare workers (HCWs) endure considerable stress. This study aims to evaluate the prevalence of long COVID infections and their influencing factors among primary HCWs after epidemic control policy adjustment in Jiangsu. A self-designed questionnaire was administered through on-site surveys among primary HCWs in five counties and districts within Jiangsu Province from July 4 to July 20, 2023. Logistic regression analysis was employed to identify factors associated with long COVID. The prevalence of long COVID among primary HCWs stood at 12.61%, with a 95% confidence interval (CI) of 11.67-13.55%. Among those affected, the most common long COVID symptoms were hypomnesia (4.90%, 95%CI: 4.29-5.51%), sleep difficulties (2.73%, 95%CI: 2.27-3.19%), fatigue (2.35%, 95%CI: 1.92-2.78%), disturbances in the reproductive system (1.93%, 95%CI: 1.54-2.32%), hair loss (1.85%, 95%CI: 1.47-2.23%), and myalgia/arthralgia (1.51%, 95%CI: 1.16-1.86%). Multivariate logistic regression revealed that older age groups (30–45 years (adjusted odds ratio (aOR) = 1.93, 95%CI: 1.44–2.58), 45–60 years (aOR = 2.82, 95%CI: 2.07–3.84)), females (aOR = 1.26, 95%CI: 1.03–1.55), and higher work stress (high stress (aOR = 1.52, 95%CI: 1.24–1.86), extremely high stress (aOR = 1.37, 95%CI: 1.03–1.82)) were more prone to long COVID. Conversely, individuals with educational attainment below the bachelor’s degree (aOR = 0.67, 95%CI: 0.55–0.82) and those who received four or more doses of the COVID-19 vaccine (aOR = 0.55, 95%CI: 0.33–0.92) were at a reduced risk. This study investigates the prevalence of long COVID among primary HCWs and identifies key influencing factors. These findings are crucial for assisting in the early identification of COVID-19 patients at risk for long-term complications, developing targ

关键词： functional state   coronavirus infection   COVID-19   athletes   cycling ergometric load   spirography   spiroergometry  

摘要： This study aimed to investigate the energy supply of athletes, who had a mild form of coronavirus infection (COVID-19) under cycling ergometric load (CEL) to substantiate the timing of recovery, as well as to determine the volume and intensity of physical activity. Eighty-seven athletes aged from 18 to 28 years old, involved in cyclic sports, were examined. Group I consisted of 52 athletes with COVID-19, and group II consisted of 37 healthy self-isolating athletes. In addition to the comprehensive examination, the tested athletes underwent special examinations: the study of diagnostic material using methods of nucleic acid amplification, spirography and spiroergometry, electrocardiography (ECG), and CEL. The results of athletes from both groups did not differ significantly ( p > 0.5) in the 1 st , 2 nd , and 3 rd examinations. The second examination revealed a discrepancy between functional reserves and the load performed, as evidenced by the difference in the recovery rate of most indicators, the results of the third examination in the long-term period (6 months) showed that the athletes of the first group did not have any violations of the parameters of the respiratory function (RF) and cardiovascular system at rest, after performing CEL, as well as in the recovery period. The results suggest that the full resumption of training loads and participation in competitions are possible only with the complete normalization of the functional state of the cardiorespiratory system. The most informative indicators are: minute ventilation (VE), heart rate (HR), oxygen pulse (OP), and coefficient of oxygen utilization (COU).

关键词： COVID-19   Ischemic stroke   Cardiovascular disease   Mendelian randomization   Genome-wide association study   IS   MR   MR-PRESSO   GWAS   SNP   LD   CVD  

关键词： plastic surgery   venous thromboembolism   deep vein thrombosis   pulmonary embolism   outcomes   COVID  

摘要： Background While plastic surgery procedures generally demonstrate a less than 2% incidence of VTE outcomes, the post-COVID era data remains elusive. This study sought to elucidate the relationship between COVID-19 infection and the risk of VTE outcomes across plastic surgery procedures. Methods Plastic surgery procedures were identified in the 2012-2022 National Surgical Quality Improvement Program databases. The outcomes of interest were the postoperative occurrence of VTE, defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), and the occurrence of any postoperative complication. Propensity score matching was used to 1) compare overall rates of VTE between pre-pandemic era and pandemic era cohorts, and 2) compare rates of VTE and overall postoperative complications in cases with and without COVID-19 diagnosis in years 2021-2022 ( p <0.05). Results 269,006 plastic surgery cases were identified, comprising largely general breast (76%) and trunk (9.4%) procedures. Non-breast free tissue transfer cases were associated with the highest rates of DVT (1.3%) and trunk procedures with the highest rates of PE (0.7%). After propensity score matching, the overall rate of VTE after the onset of the COVID-19 pandemic was not significantly different from the pre-pandemic era ( p =0.40). In a separately matched cohort, COVID-19 diagnosis did not significantly predict risk of VTE ( p =0.48) but did significantly predict risk of overall postoperative complications ( p <0.001). Conclusions While COVID-19 diagnosis itself did not predict risk of VTE upon matched analysis, it significantly predicted overall postoperative complications. Future studies may further investigate effects of COVID-19 infection over longer periods of follow up.

关键词： COVID-19   vaccination strategies   inter-dose delay   immunity waning   age-structured model  

摘要： As public health policies shifted in 2023 from emergency response to long-term COVID-19 disease management, immunization programs started to face the challenge of formulating routine booster campaigns in a still highly uncertain seasonal behavior of the COVID-19 epidemic. Mathematical models assessing past booster campaigns and integrating knowledge on waning of immunity can help better inform current and future vaccination programs. Focusing on the first booster campaign in the 2021/2022 winter in France, we used a multi-strain age-stratified transmission model to assess the effectiveness of the observed booster vaccination in controlling the succession of Delta, Omicron BA.1 and BA.2 waves. We explored counterfactual scenarios altering the eligibility criteria and inter-dose delay. Our study showed that the success of the immunization program in curtailing the Omicron BA.1 and BA.2 waves was largely dependent on the inclusion of adults among the eligible groups, and was highly sensitive to the inter-dose delay, which was changed over time. Shortening or prolonging this delay, even by only one month, would have required substantial social distancing interventions to curtail the hospitalization peak. Also, the time window for adjusting the delay was very short. Our findings highlight the importance of readiness and adaptation in the formulation of routine booster campaign in the current level of epidemiological uncertainty.