Association of Molnupiravir and Nirmatrelvir-Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19

Background Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effectiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population. Methods This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22–March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the primary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re-attendance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated. Findings In the outpatient cohort (N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritonavir, while in the inpatient cohort (N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039;Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P<0.0001). Among hospitalised patients, both antiviral prescriptions were associated with significant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P=0.031;Nirmatrelvir-Ritonavir: OR=0.47 (0.24-0.93), P=0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care. Interpretation In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrelvir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings. Funding Centre for Health Systems & Policy Research is funded by The Tung's Foundation;and The Laboratory of Data Discovery for Health Limited(D24H) is funded the AIR@InnoHK platform administered by the Innovation and Technology Commission of Hong Kong. Funders did not have any role in study design, data collection, data analysis, interpretation and writing of this manuscript.

Robust humoral and cellular immune responses in long-term convalescent COVID-19 individuals following one-dose SARS-CoV-2 inactivated vaccination

COVID-19, caused by SARS-CoV-2, has resulted in hundreds of millions of infections and millions of deaths worldwide. Preliminary results exhibited excellent efficacy of SARS-CoV-2 vaccine in preventing hospitalization and severe disease. However, data on inactivated vaccine-induced immune responses of naturally infected patients are limited. Here, we characterized SARS-CoV-2 RBD-specific IgG (anti-S-RBD IgG) and neutralizing antibodies (NAbs) against SARS-CoV-2 wild type and variants of concerns (VOCs), as well as RBD-specific IgG-secreting B cells and antigen-specific T cells respectively in 51 SARS-CoV-2 recovered subjects and 63 healthy individuals. In SARS-CoV-2 recovered patients, a single dose vaccine is sufficient to reactivate robust anti-S-RBD IgG and NAbs. The neutralizing capacity against VOCs increased significantly post-vaccination no matter healthy individuals or SARS-CoV-2 recovered patients. In addition, RBD-specific IgG-secreting B cells in SARS-CoV-2 recovered patients were significantly higher than that in healthy vaccine recipients. After the vaccine booster, the frequencies of specific IFN-γ+ CD4+ T cell, IL-2+ CD4+ T cell, and TNF-α+ CD4+ T cell responses were significantly increased in SARS-CoV-2 recovered patients. Our data highlighted the safety and utility of SARS-CoV-2 inactivated vaccine and demonstrated that robust humoral and cellular immune response can be reactivated by one-dose inactivated vaccine in SARS-CoV-2 recovered patients.

A retrospective research on non-suicidal self-injurious behaviors among young patients diagnosed with mood disorders

Background Non-suicidal self-injury (NSSI) is an emerging public concern in both clinical and non-clinical settings, especially in the background of the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, knowledge of NSSI on a certain disease entity in the later stage of the pandemic was scarce. Objective This study was conducted for the purpose of exploring the current occurrence and characteristics of NSSI in patients diagnosed with mood disorders (MDs) as well as its correlated factors in the later stage of the pandemic. Methods Three hundred and forty-nine eligible subjects (M ± SD, 21.54 ± 7.62) admitted to a mental health center in Wuhan from 11 November 2021 to 31 January 2022 were included in our study. An umbrella questionnaire comprised of demographics, COVID-19-related factors, Yale-Brown Obsessive and Compulsive Scale (Y-BOCS), Pittsburgh Sleep Quality Index-Revised (PSQI-R), Mobile Phone Addiction Index (MPAI), and Ottawa Self-injury Inventory (OSI) was extended to each subject via shared QR code. Results Of 349 patients with MDs included, 151 (43.27%) reported NSSI in the recent 1 month, among whom hand, lower arm/wrist, and scalp were the most hurt body parts, and cutting, hitting, and headbanging were the most adopted methods. “Own idea” was the most common origin of NSSI. In the logistic regression model, age bracket, family monthly income, occupation, level of obsessive-compulsive disorder (OCD) symptoms, sleep duration, withdrawal reaction to the mobile phone, and habits of using a mobile phone were independently associated with NSSI. Conclusion It was revealed by our study that NSSI was quite prevalent among patients with MDs, especially among those students, adolescents, comorbid with OCD symptoms, inadequate sleeping hours, and suffering from withdrawal reaction to mobile phones. Further research on NSSI in various psychiatric disorders and even in non-clinical settings such as the community population was in urgent need since NSSI in China was not rare.

Gender Differences in the Associations Between Physical Activity, Smartphone Use, and Weight Stigma

Background Physical activity (PA) is important for health. However, there is little evidence on how weight stigma, time spent on sedentary activities (including smartphone, social media, online learning), time spent on outdoor activity, and nomophobia associate with PA among Chinese individuals with consideration of gender. The present study examined the aforementioned associations in the COVID-19 pandemic era. Methods University students (N = 3,135;1,798 females, 1,337 males) with a mean age of 19.65 years (SD = 2.38) years completed an online survey from November to December, 2021. The online survey assessed weight stigma (using the Perceived Weight Stigma Scale and Weight Bias Internalization Scale), PA (using the International Physical Activity Questionnaire Short Form), time spent on different activities (using self-designed items for time on smartphone, outdoor activity, social media, and online learning), and nomophobia (using the Nomophobia Questionnaire). Parallel mediation models were constructed (dependent variable: PA;mediators: perceived weight stigma, weight-related self-stigma, time spent on smartphone, time spent on outdoor activity, time spent on social media, and time spent online learning;independent variable: nomophobia) and evaluated using Hayes' Process Macro Model 4 (IBM SPSS 20.0). Results Weight-related self-stigma (β = −0.06;p = 0.03), time spent on outdoor activity (β = 0.21;p < 0.001), time spent on social media (β = 0.07;p = 0.02), time spent on online learning (β = 0.06;p = 0.03), and nomophobia (β = −0.07;p = 0.01) were all significant factors explaining the PA among female participants. Perceived weight stigma (β = −0.07;p = 0.01), time spent on outdoor activity (β = 0.27;p < 0.001), and time spent on online learning (β = 0.10;p = 0.002) were all significant factors explaining PA among male participants. Conclusion Chinese healthcare providers should design programs on weight stigma reduction and outdoor activity improvement to enhance PA among university students.

Insights into the significant increase in ozone during COVID-19 in a typical urban city of China

The outbreak of COVID-19 promoted strict restrictions to human activities in China, which led to a dramatic decrease in most air pollutant concentrations (e.g., PM2.5, PM10, NOx, SO2 and CO). However, an obvious increase in ozone (O3) concentrations was found during the lockdown period in most urban areas of China. In this study, we conducted field measurements targeting ozone and its key precursors by utilizing a novel proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) in Changzhou, which is representative of the Yangtze River Delta (YRD) city cluster of China. We further applied the integrated methodology including machine learning, an observation-based model (OBM) and sensitivity analysis to obtain insights into the reasons causing the obvious increase in ozone. Major findings include the following: (1) by deweathered calculation, we found changes in precursor emissions contributed 1.46 ppbv to the increase in the observed O3 during the full-lockdown period in 2020, while meteorology constrained 3.0 ppbv of O3 in the full-lockdown period of 2019. (2) By using an OBM, we found that although a significant reduction in O3 precursors was observed during the full-lockdown period, the photochemical formation of O3 was stronger than that during the pre-lockdown period. (3) The NOx/VOC ratio dropped dramatically from 1.84 during the pre-lockdown to 0.79 in the full-lockdown period, which switched O3 formation from a VOC-limited regime to the boundary of a NOx- and VOC-limited regime. Additionally, box model results suggested that the decrease in the NOx/VOC ratio during the full-lockdown period could increase the mean O3 by 2.4 ppbv. Results of this study give insights into the relationship between O3 and its precursors in urban area and demonstrate reasons for the obvious increase in O3 in most urban areas of China during the COVID-19 lockdown period. This study also underlines the necessity of controlling anthropogenic oxygenated volatile organic compounds (OVOCs), alkenes and aromatics in the sustained campaign of reducing O3 pollution in China.

Contact-Free Operation of Epidemic Prevention Elevator for Buildings

The COVID-19 pandemic broke out in early 2020, and the infection rate of COVID-19 variants is considerably higher than that of the original virus. The pandemic is still spreading globally. In June 2021, two families living on different floors of a building in Fongshan, Kaohsiung, were simultaneously infected with COVID-19. Investigation results suggested that an elevator in buildings was the most likely place where the virus transmission occurred. Building elevators are a necessary vertical transportation facility for residents or workers in high-rise buildings, and people touch elevator buttons while operating elevators. When a passenger carrying the virus touches elevator buttons, subsequent passengers may be easily infected if they touch those buttons and then touch their mouth, eyes, or nose by accident before sanitizing or washing their hands. In this study, we developed a contact-free elevator ride system by applying smart speech recognition, contact-free perceptual buttons, gesture recognition sensors, and a web page browser activated by quick response codes to operate an elevator. This system reduces the risk of virus infection caused by contact during an elevator ride, effectively enhancing pandemic prevention and protecting people's health.

Tracking the impact of COVID-19 and lockdown policy on public mental health using social media (preprint)

The COVID-19 pandemic and its corresponding preventive and control measures have increased the mental burden on the public. Social media serve as important platforms to timely track public mental status. In this study, we conducted social-media-based analyses on temporal, geographical and occupational distributions of public mental health status during the pandemic, and how the public reacted to the lock-down policy from the perspective of mental health. We extracted 2,973,319 mental health-related tweets of 1,778,140 users from February 1, 2020 to September 30, 2021. We found that, compared to the general public, healthcare workers had higher concerns on three types of mental health problems (depression, insomnia, addiction) (P<0.001) and focused more on clinical topics while the public worried more about daily life issues. The lockdown policy in New York was correlated with a proportional decrease of mental health-related tweets, while Florida had an opposite correlation (both P<0.05). Our findings indicated that the mental burden brought by the pandemic varied across occupations and locations and changed over time.

Neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2 (preprint)

Antibody therapeutics for the treatment of COVID-19 has been highly successful while faces a challenge of the recent emergence of the Omicron variant which escapes the majority of existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of which, nAbs X01, X10 and X17 showed broadly neutralizing breadths against most variants of concern (VOCs) and X17 was further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-EM structures of three-antibody in complex with the spike proteins of prototyped SARS-CoV-2, Delta, Omicron and SARS-CoV defined three non-overlapping conserved epitopes on the receptor-binding domain (RBD). The triple antibody cocktail exhibited enhanced resistance to viral escape and effective protection against the infection of Beta variant in hamsters. Our finding will aid the development of both antibody therapeutics and broad vaccines against SARS-CoV-2 and emerging variants.

Effectiveness of a Brief Mindfulness-Based Intervention of “STOP" (Stop, Take a Breath, Observe, Proceed) Touching Your Face” During the COVID-19 Pandemic: Randomised Controlled Trial (preprint)

Background: Avoid touching our eyes, nose, and mouth (T-zone) is one of recommended strategies to reduce the spread of the coronavirus disease 2019 (COVID-19) and other infectious diseases. However, face-touching is a frequent behaviour, and it is often done automatically without self-awareness. Raising self-awareness of habituated face-touching behaviour may help individuals to avoid face-touching by contaminated hands. Our aim was to evaluate whether mindfulness-based brief behaviour-change intervention (MBI) named “STOP (Stop, Take a Breath, Observe, Proceed) touching your face” can reduce face-touching behavior. Methods: In this online-based, two group, wait-list, randomized controlled trial, participants aged 18 years or more from general population in China were recruited via Chinese social media platforms. Eligible participants were randomly assigned in a 1:1 ratio to receive “STOP touching your face” intervention or control intervention. Those researchers who assessing outcomes were masked to group allocation. A 60-minute self-monitoring of face-touching behaviour was required to report in the pre- and post-intervention. Reduction of percentage of T-Zone touching was set as primary outcome, with reduction of face-touching frequency being a key secondary outcome. These outcomes were analysed in the intention-to-treat (ITT) basis with a complete case analysis (CCA). Safety was monitored in all randomly assigned participants. This trial is registered at ClinicalTrials.gov (Trial registration number: NCT04330352), and is completed. Findings: Between April 2, 2020 to July 2, 2020, 10194 participants were invited to the trial. Of these, we recruited and randomly assigned 1090 (10.7%) participants to the “STOP touching your face” intervention group (n=545) or to the wait-list control intervention (comparator) group (n=545) after reporting the first 60-minute self-monitoring of face-touching behaviour (pre-intervention). Among them, 71.6% (n=390) participants from the intervention group and 63.9% (n=348) from the control group reported the second 60-minute self-monitoring of face-touching behaviour (post-intervention). ITT analysis revealed that percentage of T-Zone touching was significantly reduced by 8.1% in the intervention group (from 81.1% to 73.0%, RR=0.901, OR=0.631, RD=-0.081, p=0.002), and insignificantly reduced by 0.6% in the control intervention (from 80.0% to 79.4%, p=0.821). Group comparison showed that fewer participants had T-Zone touching in the intervention group than that in the control group (73.0% vs 79.4%, RR=0.919, OR=0.700, RD=-0.064, p=0.015) after intervention, and that there was more reduction of T-Zone touching frequency in the intervention group than that in the control group (mean ± SD: 1.7 ± 5.13 vs 0.7 ± 3.98, Mean difference (95% CI): 1.03 (0.48 to 1.58), p<0.001, Cohen's d=-0.218). The above results were further confirmed by CCA. Compared with older individuals (≥30 years old), young adults (18–29 years old) have twice risk of having T-Zone touching behaviour (OR=2.029, 95% CI=1.145 to 3.597, p=0.015), and younger participants reduced face-touching frequency more than their older counterparts (mean ± SD: 9.9 ± 14.24 vs 3.6 ± 11.25, Mean difference (95% CI)=6.270 (3.615 to 8.924), p<0.001, Cohen's d=-0.47). Interpretation This trial is the first to evaluate the efficacy of “STOP touching your face” intervention to reduce face-touching behaviour during the outbreak of COVID-19. The findings of significantly reduced T-Zone touching behaviour in the intervention group supports the widely dissemination of this brief and simple mindfulness-based behaviour-change intervention to low the risk for the COVID-19 and other hand-to face-touching infectious diseases.Trial registration number: NCT04330352Trial Registration. Funding: Zhejiang University, number (2020XGZX046). Declaration of Interest: We declare no competing interests.Ethical Approval: The trial was approved by The Ethics Committee of Sir Run Run Shaw hospital, an affiliate of Zhejiang University, Medical College (NO. 20200401-32).

The collaboration between infectious disease modeling and public health decision-making based on the COVID-19

Public health decision-making may have great uncertainty especially in dealing with emerging infectious diseases, so it is necessary to establish a collaborative mechanism among modelers, epidemiologists, and public health decision-makers to reduce the uncertainty as much as possible. We searched the relevant studies on transmission dynamics modeling of infectious diseases, SARS, MERS, and COVID-19 as of March 1, 2021 based on PubMed. We compared the key health decision-making time points of SARS, MERS, and COVID-19 prevention and control, and the publication time points of modeling research, to reveal the collaboration between infectious disease modeling and public health decision-making in the context of the COVID-19 pandemic. Searching with infectious disease and mathematical model as keywords, there were 166, 81 and 1 289 studies on the modeling of infectious disease transmission dynamics of SARS, MERS, and COVID-19 were retrieved respectively. Based on the modeling application framework of public health practice proposed in the current study, the collaboration among modelers, epidemiologists and public health decision-makers should be strengthened in the future.

A Panel Regression Analysis for the COVID-19 Epidemic in the United States: From the Quarantine Policy and Environmental Perspective (preprint)

Background. The COVID-19 epidemic has had an extreme impact on society. This study aimed to discuss this epidemic in the U.S. and explore the association between COVID-19 daily incidence rate and influencing factors including people’s implementation of states’ quarantine policy and environmental factors including temperature, humidity and so on.Methods. Data of 50 states in U.S. were used as the research subjects. A panel data model was established based on the daily incidence rate and influencing factors from 15 March to 30 September, 2020. The period was analyzed both unsegmented and segmented. The k-means clustering method was used to cluster the states, and panel linear regression method was used for correlation analysis.Results. The characteristics of the daily incidence rate and factors of the three categories were different after clustering. The daily residents at home, proportion of travel people, humidity and incidence rate were negatively correlated, while the daily temperature and incidence rate were positively correlated after unsegmented multivariate analysis. While after segmented analysis, the air pressure and the temperature showed a trend that was negatively correlated with the daily incidence rate respectively in the first and the fifth segment, other indicators showed the analogous results. At the same time, this study also completed the regression analysis after classification of the three groups. Compared with results without classification, there was a decrease of the number of significant independent variables.Conclusions. The spread of COVID-19 in 50 states in U.S. was related to quarantine measures, temperature and humidity. The progress of the epidemic would be relatively slow if people chose to stay at home. Besides, the increase in temperature (＜84.2℉) could be conducive to the spread of the epidemic, while the increase in relative humidity (40~70%) might inhibit the spread of the virus to a certain degree.

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine (KCONVAC) in Healthy Adults: Two Randomized, Double-blind, and Placebo-controlled Phase 1/2 Clinical Trials (preprint)

Background The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. Methods Two phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. Findings In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87.5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83.0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29.3 to 49.1 at Day 0/14 regimen and from 100.2 to 131.7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69.4 to 118.7 at Day 0/14 regimen and from 153.6 to 276.6 at Day 0/28 regimen, and RBD-IgG ranged from 605.3 to 1169.8 at Day 0/14 regimen and from 1496.8 to 2485.5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56.5% (13/23) and 62.5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. Interpretation KCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. Funding Guandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.

In vitro inactivation of SARS-CoV-2 by commonly used disinfection products and methods.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is currently a global pandemic, and there are limited laboratory studies targeting pathogen resistance. This study aimed to investigate the effect of selected disinfection products and methods on the inactivation of SARS-CoV-2 in the laboratory. We used quantitative suspension testing to evaluate the effectiveness of the disinfectant/method. Available chlorine of 250 mg/L, 500 mg/L, and 1000 mg/L required 20 min, 5 min, and 0.5 min to inactivate SARS-CoV-2, respectively. A 600-fold dilution of 17% concentration of di-N-decyl dimethyl ammonium bromide (283 mg/L) and the same concentration of di-N-decyl dimethyl ammonium chloride required only 0.5 min to inactivate the virus efficiently. At 30% concentration for 1 min and 40% and above for 0.5 min, ethanol could efficiently inactivate SARS-CoV-2. Heat takes approximately 30 min at 56 °C, 10 min above 70 °C, or 5 min above 90 °C to inactivate the virus. The chlorinated disinfectants, Di-N-decyl dimethyl ammonium bromide/chloride, ethanol, and heat could effectively inactivate SARS-CoV-2 in the laboratory test. The response of SARS-CoV-2 to disinfectants is very similar to that of SARS-CoV.

Career Choice Regret During COVID-19 Among Healthcare Students and Professionals in Mainland China: A Cross-Sectional Study (preprint)

BackgroundThe COVID-19 epidemic affected the career choice of healthcare professionals and students. To explore career choice regret of healthcare professionals and students during COVID-19 outbreak and its affected factors.MethodsConvenience sample of nurses, doctors, and medical students were recruited from hospitals and universities nationwide. The data collected including demographic information, professional value before and after the COVID-19 outbreak, the Connor-Davidson Resilience Scale, and career choice regret level by an online questionnaire. Multinominal logistic regression was employed to explore the factors associated with career choice regret.ResultsIn total, 9322 participants of convenience sampling were enrolled in, including 5786 nurses, 1664 doctors, and 1872 medical students. 6.7% participants had career choice regret. Multinominal logistic regression analysis showed, compared to participants with no regret, that as levels of resilience increased, the odds of experiencing career choice regret decreased (OR=0.951,P＜0.001), while participants with lower professional value evaluation after the COVID-19 outbreak had higher probability to experience career choice regret(OR=1.552,P＜0.001). Medical students were more likely to regret than nurses (OR=1.654,P=0.002), participants whose career/major choice was according to their personal ideal had higher risk of experience career choice regret (OR=1.592,P＜0.001), while participants who were very afraid of the coronavirus had higher risk to experience career choice regret then participants with no fear at all(OR=1.997,P=0.004).As for the medical students, results indicated that medical students major in nursing and undergraduates had higher risk to experience career choice regret compared to medical students major in clinical medicine and postgraduate (Master or PhD), with an odds ratios of 2.645 and 6.851 respectively.ConclusionsA minority of healthcare professionals and medical students regretted their career choices during the COVID-19 outbreak. Enhance personal psychological resilience and professional value would helpful to reduce career choice regret among healthcare professionals and students during pandemic.

Diversity of ACE2 and its interaction with SARS-CoV-2 receptor binding domain (preprint)

COVID-19, the clinical syndrome caused by the SARS-CoV-2 virus, has rapidly spread globally causing millions of infections and hundreds of thousands of deaths. The potential animal reservoirs for SARS-CoV-2 are currently unknown, however sequence analysis has provided plausible potential candidate species. SARS-CoV-2 binds to the angiotensin I converting enzyme 2 (ACE2) to enable its entry into host cells and establish infection. We analyzed the binding surface of ACE2 from several important animal species to begin to understand the parameters for the ACE2 recognition by the SARS-CoV-2 spike protein receptor binding domain (RBD). We employed Shannon entropy analysis to determine the variability of ACE2 across its sequence and particularly in its RBD interacting region, and assessed differences between various species ACE2 and human ACE2. As cattle are a known reservoir for coronaviruses with previous human zoonotic transfer, and has a relatively divergent ACE2 sequence, we compared the binding kinetics of bovine and human ACE2 to SARS-CoV-2 RBD. This revealed a nanomolar binding affinity for bovine ACE2 but an approximate ten-fold reduction of binding compared to human ACE2. Since cows have been experimentally infected by SARS-CoV-2, this lower affinity sets a threshold for sequences with lower homology to human ACE2 to be able to serve as a productive viral receptor for SARS-CoV-2.

The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody (preprint)

SARS-CoV-2-neutralizing antibodies are promising therapeutics for COVID-19. However, little is known about the mechanisms of action of these antibodies or their effective dosing windows. We report the discovery and development of SC31, a potent SARS-CoV-2 neutralizing IgG1 antibody, originally isolated from a convalescent patient at day 27 after the onset of symptoms. Neutralization occurs via a binding epitope that maps within the ACE2 interface of the SARS-CoV-2 Spike protein, conserved across all common circulating SARS-CoV-2 mutants. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, SC31 demonstrated potent survival benefit by dramatically reducing viral load concomitant with attenuated pro-inflammatory responses linked to severe systemic disease, such as IL-6. Comparison with a Fc-null LALA variant of SC31 demonstrated that optimal therapeutic efficacy of SC31 requires intact Fc-mediated effector functions that can further induce an IFN{gamma}-driven anti-viral immune response. Dose-dependent efficacy for SC31 was observed down to 5mg/kg when dosed before the activation of lung inflammatory responses. Importantly, despite Fc{gamma}R binding, no evidence of antibody dependent enhancement was observed with the Fc-competent SC31 even at sub-therapeutic doses. Therapeutic efficacy was confirmed in SARS-CoV-2-infected hamsters, where SC31 again significantly reduced viral load, decreased lung lesions and inhibited progression to severe disease manifestations. This study underlines the potential for significant COVID-19 patient benefit for the SC31 antibody that justifies rapid advancement to the clinic, as well as highlighting the importance of appropriate mechanistic and functional studies during development. One Sentence SummaryAnti-SARS-CoV-2 IgG1 antibody SC31 controls infection in vivo by blocking SP:ACE2 binding and triggering a Fc-mediated anti-viral response.

The application of WeChat applet and integrity propaganda and education in outpatient pre-examination during the prevalence of COVID-19 / 医学研究生学报

ObjectiveDuring the prevention and control of COVID-19, it is a difficult problem to obtain the individual epidemiological status of outpatients efficiently and accurately in a large comprehensive third-grade class-A hospital. To discuss the application and effect of WeChat applet and integrity propaganda and education in outpatient pre-examination during the prevention and control of COVID-19.MethodsFirstly, the outpatients were treated with integrity propaganda and education (like informing the law and regulations, recording the personal credit) at the outpatient pre-examination office. Secondly, let them take real-name authentication in the hospital self-developed WeChat applet. Thirdly, the outpatients filled in the epidemiological questionnaire related to COVID-19 by WeChat. The differences between before using the application (8,186 patients) and after using (7,361 patients) were compared in pre-examination time and concealing the incidence of an individual's epidemiological history.ResultsAfter the application of WeChat applet and integrity propaganda and education, the pre-examination time after using application [(1.07±0.23)min] was shorter than that before using[(2.15±0.37) min] (P<0.05). The concealment rate of epidemiological history was 0.05% before using application and zero after using.ConclusionWeChat applet and integrity propaganda and education can shorten the pre-examination time of covid-19 and reduce the occurrence of concealing personal epidemiological history.

Analysis of the management measures and effects in prevention and control of COVID-19 in outpatient service of a general hospital / 医学研究生学报

To preliminarily analyze the prevention and control of COVID-19, a general hospital outpatient service took six management measures, including setting up a leading group, building rules and regulations, infection control and supervision, special training, humanized service, public opinion propaganda. After nearly two months, the rates of both body temperature monitoring and epidemiological history screening are 100%, the medical staff infection rate is zero, and no cross infection between the patients due to adopting outpatient service comprehensive management measures which had strong organization and leadership, effective targeted training, effective control of all links in epidemic prevention and control work. During the fight against COVID-19, outpatient management played an important role in hospital management. The above approaches provide valuable experience for preventing the spread of infectious diseases effectively and winning the biological weapon wars in the future.

Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients (preprint)

Recent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16- NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.