Investigation and analysis of current situation of rehabilitation therapists in Hunan province after the COVID-19 epidemic: a cross-sectional study (preprint)

Background This study aims to comprehend the prevailing circumstances of rehabilitation therapists in the aftermath of the COVID-19 outbreak and to analysis the variables that affect the job satisfaction of these therapists who volunteered to take part in this study. In total, 769 rehabilitation were enrolled in the study.Method Based on the experts' discussions and revisions at the Xiangya Boai Rehabilitation Hospital, this questionnaire was subsequently distributed to rehabilitation therapists via WeChat. rehabilitation were sampled using a cross-sectional approach on Wenjuanxing through the WeChat APP.Results Based on an analysis of data distribution and composition ratio, it is evident that there have been significant transformations in multiple data dimensions between pre-pandemic therapy and the current era. Comparative analyses revealed statistically significant differences in age (H = 32.90, P < 0.001), years of working experience (H = 32.14, P < 0.001), job title (H = 29.93, P < 0.001), and monthly salary level (H = 114.81, P < 0.001). Further analyses using multiple factor regression indicated that monthly income significantly influenced the outcome measure. Participants with a monthly income below 3,000 yuan had a significantly higher Odds Ratio (OR) of 17.9 (OR = 17.95, 95%CI 8.49–38.29, P < 0.001) for experiencing job dissatisfaction compared to those with a monthly income exceeding 10,000 yuan. Similarly, therapists earning between 3,000 and 5,000 yuan monthly had an OR of 5.3 (OR = 5.32, 95%CI 2.91–9.83, P < 0.001) for job dissatisfaction, while those in the 5,001–7,000 yuan income range had an OR of 2.46 (OR = 2.46, 95%CI 1.36–4.49, P < 0.05).Conclusion After the epidemic, the distribution of age, gender, hospital type, and job title among rehabilitation therapists has changed. The job classification of therapists has become more refined, and the monthly income level has become an important factor affecting job satisfaction. The forefront of this academic endeavor lies in carefully investigate the existing landscape that defines rehabilitation therapists in Hunan, which will provide a deeper insight into whole China's community of therapists.

Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study (preprint)

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines.Methods: A transcriptomic analysis of the immune response to the Covid-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells (PBMCs) was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and seven days after the second dose (V2D7) using anti-Spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified six months after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response.Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with predominant T cell activity in controls one week after the first vaccination dose, compared to predominant myeloid cell activity in HD at this time point. HD demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p < 0.05). Anti-spike IgG remained elevated above baseline at six months in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.Conclusion: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects (HD) comparable to healthy controls (HC) and identify transcriptomic and clinical predictors of anti-Spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of end stage renal disease (ESRD). Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003

Do COVID-19 Pandemic-Related Behavior Changes Affect Perioperative Respiratory Adverse Events in Children Undergoing Cardiac Interventional Catheterization? (preprint)

Background: The Novel Coronavirus Disease (COVID-19) pandemic-related behavior changes could affect the perioperative respiratory adverse events in children with congenital heart disease (CHD). This study was designed to compare the incidence of perioperative respiratory adverse events (PRAEs) in children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during COVID-19 pandemic.Methods：COVID-19 was outbreak in January 2020 in China. 260 pediatric patients scheduled for elective therapeutic cardiac catheterization were included from January 2019 to March 2021 and 154 were completed during the pandemic. Recent URI was diagnosed by the attending anesthesiologist owing to different PRAEs incidence in non-URI and URI children. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing the elective cardiac catheterization were compared before and during the COVID-19 pandemic. Logistic regression model was fitted to identify the potential risk factors associated with PRAEs. Results: Of 564 children enrolled, 359 completed the study and was analyzed finally. URI incidence decreased substantially during the COVID-19 pandemic (14% vs. 41%, P <0.001). Meanwhile, the overall PRAEs also significantly declined no matter whether or not the child had recent URI (22.3% vs. 42.3%, P =0.001 for non-URI and 29.2% vs. 58.7%, P =0.012 for URI respectively). Post-operative agitation in non-URI children occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P =0.001). Behaviors before the COVID-19 pandemic (odd ratio=2.84, 95%CI 1.76 to 4.58) and recent URI (odd ratio =1.79, 95%CI 1.09 to 2.92) were associated with the PRAEs. Conclusions: COVID-19 pandemic-related behavior changes were associated with the reduction of PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.

AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans (preprint)

Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non-overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for [≥]3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1-2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.

Home Sweet Home: Working from Home and Employee Performance during the COVID-19 Pandemic in the UK (preprint)

In 2020, the COVID-19 pandemic forced governments in many countries to ask employees to work from home (WFH) where possible. Using representative data of the employed respondents from the UK, we find that the pandemic-led increases in WFH frequency are associated with a higher self-perceived hourly productivity, notably among female employees working in occupations conducive to WFH. Interestingly, changes in WFH frequency are unrelated to the respondents' weekly working hours (and weekly wages) during the same period. We then perform effect heterogeneity analysis by separately focusing on males and females working in WFH feasible occupations. For males, we find that the WFH-productivity correlation is stronger among those who commuted larger distances (and spent longer commuting time) to the office before the pandemic. For females, while we observe a stronger WFH-productivity correlation among those with higher autonomy over work pace, a weaker correlation is found among mothers with school-age children, mainly due to increased homeschooling needs during the pandemic. Finally, looking at the future of WFH, we show that employees' recent WFH experience and subsequent hourly productivity are intimately associated with their desire to undertake WFH in the future.

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the alpha-helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

The Effect of Large-Scale Anti-Contagion Policies on the Coronavirus (COVID-19) Pandemic (preprint)

Governments around the world are responding to the novel coronavirus (COVID-19) pandemic1 with unprecedented policies designed to slow the growth rate of infections. Many actions, such as closing schools and restricting populations to their homes, impose large and visible costs on society, but their benefits cannot be directly observed and are currently understood only through process-based simulations.2-4 Here, we compile new data on 1,717 local, regional, and national non-pharmaceutical interventions deployed in the ongoing pandemic across localities in China, South Korea, Italy, Iran, France, and the United States (US). We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth, 5,6 to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of roughly 38% per day. We find that anti-contagion policies have significantly and substantially slowed this growth. Some policies have different impacts on different populations, but we obtain consistent evidence that the policy packages now deployed are achieving large, beneficial, and measurable health outcomes. We estimate that across these six countries, interventions prevented or delayed on the order of 62 million confirmed cases, corresponding to averting roughly 530 million total infections. These findings may help inform whether or when these policies should be deployed, intensified, or lifted, and they can support decision-making in the other 180+ countries where COVID-19 has been reported.7