Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.

Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.

The relation between autonomy support and music enjoyment in online learning for music undergraduates in the post-COVID-19 era.

Music enjoyment is considered to predict music-related academic performance and career choice. Although relevant research in non-music fields has demonstrated the association between teachers' autonomy support and students' academic enjoyment, it remains unknown whether this association is valid in the music discipline. In addition, in the post-COVID-19 era, online education has become a common way of teaching and learning for music undergraduates. In the form of online learning, the mechanisms mediating teachers' music autonomy support and students' music academic enjoyment are also unknown. This study draws on Pekrun's theory of achievement emotions and control values to explore the mediating role of attributions and values in the association between autonomous support and academic achievement. In this study, 270 undergraduates majoring in music eventually completed the online surveys. Results from structural equation modeling indicated that autonomy support positively predicted music enjoyment and that attributions (i.e., internal attribution and external attribution) and values (i.e., intrinsic value, attainment value, utility value) mediated the association between autonomy support and music enjoyment. The findings also provide insights into possible avenue for promoting music enjoyment emotion during online teaching in the post-COVID-19 era. Implications and limitations are discussed in the study.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China

Background To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown;the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

Willingness to Receive a COVID-19 Vaccine and Associated Factors among Older Adults: A Cross-Sectional Survey in Shanghai, China.

BACKGROUND: Older individuals have a high risk of morbidity and mortality due to COVID-19, and one of the most effective ways to prevent COVID-19 is vaccination. Little is known about older people's willingness to receive a COVID-19 vaccine. Therefore, the objective of this study was to assess the acceptance of and factors influencing the intention to receive a COVID-19 vaccination among older adults in Shanghai, China. METHODS: A cross-sectional study was conducted among older adults (≥60 years old) in Shanghai. Face-to-face interviews with a questionnaire were conducted in community health service centers, recording several parameters: demographic information, health-related factors; perceived likelihood, severity, and burden of COVID-19; perceived safety, effectiveness, necessity, and benefit of the COVID-19 vaccine, as well as their trust in the vaccine delivery system and doctors; willingness to receive a COVID-19 vaccination. Bivariate analysis between several survey items and the willingness to receive a COVID-19 vaccination was conducted using a chi-square test. Logistic regression was used to assess to what degree each variable affected the willingness to receive a COVID-19 vaccination. RESULTS: Of the 1067 participants, 90.91% (970/1067) confirmed that they were willing to receive a COVID-19 vaccination. The participants were more likely to be willing to be vaccinated if they were immigrants (OR = 1.988, 95%CI = 1.062-3.717), had an education level of junior high school (OR = 2.724, 95%CI = 1.000-7.423) or high school or above (OR = 3.993, 95%CI = 1.576-10.119), and had a monthly income of CNY 3000-5000 (OR = 32.770, 95%CI = 1.144-6.711) or CNY >5000 (OR = 2.309, 95%CI = 1.003-5.319). The participants were also more likely to be willing to be vaccinated if they had received a pneumonia vaccination previously (OR = 2.138, 95%CI = 1.016-4.500), perceived the safety of the COVID-19 vaccine (OR = 1.508, 95%CI = 1.073-2.119), perceived the necessity of the COVID-19 vaccine (OR = 2.604, 95%CI = 1.946-3.484), or trusted the suggestions of doctors (OR = 1.706, 95%CI = 1.115-2.618). The participants were less likely to be willing to be vaccinated if they were aged ≥76 years (OR = 0.498, 95%CI = 0.264-0.939), reported a physical health condition of bad or below (OR = 0.229, 95% CI = 0.095-0.549), or were worried about the adverse effects of a COVID-19 vaccination (OR = 0.503, 95%CI = 0.364-0.695). CONCLUSIONS: Under the free vaccination policy for COVID-19, older adults have a high intention to be vaccinated to prevent COVID-19 in Shanghai, China. Widely publicizing the safety and necessity of COVID-19 vaccination is necessary.

Global Inequality in Service Sector Development: Trend and Convergence

The COVID-19 pandemic has caused a huge impact on global service sector. In the pandemic background, to understand the disparity in service sector outputs at the global level is crucial for assessing the effectiveness of development policies in different countries. This study investigate the global service sector and it aims to investigate the transitional dynamics of the output from the service sector by adopting stochastic kernel analyses. Distribution dynamics analyses are carried out for all the countries in the world. The data are then divided into different regional and income groups to evaluate the impacts of geographical location and income on the development of the service sector. The results show that the Global North will continue to make greater strides, while the output capacity in many Global South countries struggles to reach the global average. Moreover, it is shown that countries with higher per capita income will perform better in the development of their service sector than those with low per capita income, thereby highlighting the persistence of global inequality. Finally, this study shows that the Sub-Saharan Africa region and the South Asia region both are very important in the alleviation of global inequality.

Epidemiological, Virological and Serological Features of Coronavirus Disease 2019 (COVID-19) Cases in People Living With Human Immunodeficiency Virus in Wuhan: A Population-based Cohort Study.

BACKGROUND: We aimed to describe the epidemiological, virological, and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus (HIV; PLWH). METHODS: This population-based cohort study identified all COVID-19 cases among all PLWH in Wuhan, China, by 16 April 2020. The epidemiological, virological, and serological features were analyzed based on the demographic data, temporal profile of nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the disease, and SARS-CoV-2-specific immunoglobin (Ig) M and G after recovery. RESULTS: From 1 January to 16 April 2020, 35 of 6001 PLWH experienced COVID-19, with a cumulative incidence of COVID-19 of 0.58% (95% confidence interval [CI], .42-.81%). Among the COVID-19 cases, 15 (42.86) had severe illness, with 2 deaths. The incidence, case-severity, and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. There were 197 PLWH who had discontinued combination antiretroviral therapy (cART), 4 of whom experienced COVID-19. Risk factors for COVID-19 were age ≥50 years old and cART discontinuation. The median duration of SARS-CoV-2 viral shedding among confirmed COVID-19 cases in PLWH was 30 days (interquartile range, 20-46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (<20 copies/ml; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs 0.11, respectively [P < .001]; median S/CO for IgG, 10.16 vs 17.04, respectively [P = .069]). CONCLUSIONS: Efforts are needed to maintain the persistent supply of antiretroviral treatment to elderly PLWH aged 50 years or above during the COVID-19 epidemic. The coinfection of HIV and SARS-CoV-2 might change the progression and prognosis of COVID-19 patients in PLWH.

Better strategies for containing COVID-19 pandemic: a study of 25 countries via a vSIADR model.

We study epidemiological characteristics of 25 early COVID-19 outbreak countries, which emphasizes on the reproduction of infection and effects of government control measures. The study is based on a vSIADR model which allows asymptomatic and pre-diagnosis infections to reflect COVID-19 clinical realities, and a linear mixed-effect model to analyse the association between each country's control measures and the effective reproduction number R t . It finds significant effects of higher stringency measures in lowering the reproduction, and a significant shortening effect on the time to the epidemic turning point by applying stronger early counter measures. Epidemic projections under scenarios of the counter measures (China and Korea, the USA and the UK) show substantial reduction in the epidemic size and death by taking earlier and forceful actions. The governments' response before and after the start of the second wave epidemics were alarmingly weak, which made the average duration of the second wave more than doubled that of the first wave. We identify countries which urgently need to restore to at least the maximum stringency measures implemented so far in the pandemic in order to avoid even higher infection size and death.

COVID-19 and coagulation dysfunction in adults: A systematic review and meta-analysis.

The outbreak of 2019 novel coronavirus disease (COVID-19) has posed a grave threat to the global public health. The COVID-19-induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta-analysis and systematically review the blood coagulation indicators in patients with severe COVID-19. A meta-analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID-19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = -24.83, 95% confidence interval [CI]: -34.12 to -15.54; P < .001), d-dimer (WMD = 0.19, 95% CI: 0.09-0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50-1.54; P < .001) were significantly associated with the severity in patients with COVID-19. The meta-analysis revealed that no correlation was evident between an increased severity risk of COVID-19 and activated partial thromboplastin time (WMD = -1.56, 95% CI: -5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: -0.13 to 0.51; P = .243). The single arm meta-analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38-172.85] vs 190.09 [95% CI: 179.45-200.74]), higher d-dimer (0.49 [95% CI: 0.33-0.64] vs 0.27 [95% CI: 0.20-0.34]), and higher fibrinogen (4.34 [95% CI: 1.98-6.70] vs 3.19 [95% CI: 1.13-5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID-19, in which low platelet, high d-dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID-19 cases.

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.

Analysis and evaluation of 670 convalescent plasma samples from patients with COVID-19 infection

Objective: To systematically analyze the 670 convalescent plasma (CP) samples from patients with coronavirus disease 2019 (COVID-19).

Brief Report: Virologic and Immunologic Outcomes for HIV Patients With Coronavirus Disease 2019.

BACKGROUND: To describe the virologic and immunologic outcomes among people living with HIV (PLHIV) coinfected with SARS-CoV-2. SETTING: Wuhan, China. METHODS: Thirty-five coinfected patients were identified by matching the reported cases in National Notifiable Infectious Disease Report system for COVID-19 and HIV in Wuhan by time of April 19, 2020. Questionnaire-based survey and follow-up with blood sample collection were used to obtain characteristics before COVID-19 and after recovery. Nonparametric Mann-Whitney U test, χ2, or Fisher exact test, Mcnemar test, and Wilcoxon test were conducted. RESULTS: Twenty of the 35 coinfected patients were identified as asymptomatic/mild/moderate COVID-19 (nonsevere group) and 15 were identified as severe/critical (severe group). The severe and nonsevere group had no differences in demographics, HIV baseline status, the intervals between last tests and follow-up tests for CD4+ cell count and HIV-1 viral load (all P > 0.05). Overall, there was a significantly increased number of coinfected patients with HIV-1 viral load ≥20 copies/mL after recovery (P = 0.008). The median viral load increased significantly after recovery in severe group (P = 0.034), whereas no significant change of HIV-1 viral load was observed in the nonsevere group. Limited change of CD4+ cell count was found (all P > 0.05). CONCLUSION: The coinfection of SARS-CoV-2 may put PLHIV at greater risk for HIV-1 viral rebound especially for severe/critical COVID-19, whereas it had limited impacts on CD4+ cell count. Whether continuous antiretroviral therapy against HIV infection would have significant impacts on CD4+ cell count among PLHIV coinfected with SARS-CoV-2 needs further research.

Tracking Reproductivity of COVID-19 Epidemic in China with Varying Coefficient SIR Model

We propose a varying coefficient Susceptible-Infected-Removal (vSIR) model that allows changing infection and removal rates for the latest corona virus (COVID-19) outbreak in China. The vSIR model together with proposed estimation procedures allow one to track the reproductivity of the COVID-19 through time and to assess the effectiveness of the control measures implemented since Jan 23 2020 when the city of Wuhan was lockdown followed by an extremely high level of self-isolation in the population. Our study finds that the reproductivity of COVID-19 had been significantly slowed down in the three weeks from January 27th to February 17th with 96.3% and 95.1% reductions in the effective reproduction numbers R among the 30 provinces and 15 Hubei cities, respectively. Predictions to the ending times and the total numbers of infected are made under three scenarios of the removal rates. The paper provides a timely model and associated estimation and prediction methods which may be applied in other countries to track, assess and predict the epidemic of the COVID-19 or other infectious diseases.

Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China.

The novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95% CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had a higher burden than the 2009 influenza pandemic or seasonal influenza in terms of hospitalization and mortality rates, and clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1,178 SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most of transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.

The SARS-CoV-2 RNA with mild pulmonary consolidation lasts longer in non-severe COVID-19 patients: an observational study (preprint)

Background: Since December 2019, COVID-19 has rapidly swept the world. It is particularly important to understand the dynamic changes of the whole disease course of non-severe patients from the onset to the follow-up after discharge.Methods: On February 1, 2020, 18 cases of non-severe COVID-19 appeared in a hospital in Beijing. All patients were SARS-CoV-2 RNA positive by RT-PCR for pharyngeal swabs. We recorded the clinical information and viral dynamics of these patients from the onset of the disease to 2 months after discharge. According to the severity of lung consolidation, 18 patients were divided into two groups (mild pulmonary consolidation group [imaging score ≤10]; severe pulmonary consolidation group [imaging score >10]).Results: Eighteen patients (median age 43) were included, including 14 females. Fever (11/18) and cough (8/18) were the most common symptoms. The duration of SARS-CoV-2 RNA positive in mild pulmonary consolidation group was significantly longer than severe pulmonary consolidation group (the median time was 30 days and 13 days, respectively, P= 0.0031). Two months after discharge, almost all patients were followed up for IgM antibody disappearance and IgG antibody production.Conclusion: In non-severe COVID-19 patients, the positive duration of the SARS-CoV-2 RNA in patients with mild pulmonary consolidation was longer than the severe pulmonary consolidation. However, it is necessary for a large sample to verify our conclusions.

Case fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China

OBJECTIVE: To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. METHODS: We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from December 29, 2019 to April 17, 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and lognormal distributions to time-to-event data using maximum-likelihood estimation. RESULTS: We analyzed 82,719 laboratory-confirmed cases reported in mainland China, including 4,632 deaths, and 77,029 discharges. The estimated CFR was 5.65% (95%CI: 5.50%-5.81%) nationally, with highest estimate in Wuhan (7.71%), and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients, and 0.8-10.3 fold higher than that of mild-to-severe patients. Older age (OR 1.14 per year;95%CI: 1.11-1.16), and being male (OR 1.83;95%CI: 1.10-3.04) were risk factors for mortality. The time from symptom onset to first healthcare consultation, time from symptom onset to laboratory confirmation, and time from symptom onset to hospitalization were consistently longer for deceased patients than for those who recovered. CONCLUSIONS: Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.

Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020 (preprint)

Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.