Environmental impact assessment for the use of an orally aerosolised adenovirus type-5 vector-based COVID-19 vaccine in randomised clinical trials.

BACKGROUND: An orally aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolised Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the setting desks of the vaccine nebuliser, mask samples from participants and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type SARS-CoV-2 strain in serum were detected. RESULTS: Only one (4.00%) air samples collected before the initiation of vaccination was positive, which were almost positive during and after the vaccination (97.96%, 100%, respectively). All nurses in the trial A showed at least four-fold increase of the neutralizing antibody against the SARS-CoV-2 after the initiation of the study. In trial B, the positive proportion of the mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7, respectively. CONCLUSION: The vaccination with the orally aerosolised Ad5-nCoV could have some spillage of the vaccine vector viral particles in the environment and cause human exposure.

Electrospun PVB/AVE NMs as mask filter layer for win-win effects of filtration and antibacterial activity.

The COVID-19 pandemic has caused serious social and public health problems. In the field of personal protection, the facial masks can prevent infectious respiratory diseases, safeguard human health, and promote public safety. Herein, we focused on preparing a core filter layer for masks using electrospun polyvinyl butyral/apocynum venetum extract nanofibrous membranes (PVB/AVE NMs), with durable interception efficiency and antibacterial properties. In the spinning solution, AVE acted as a salt to improve electrical conductivity, and achieve long-lasting interception efficiency with adjustable pore size. It also played the role of an antibacterial agent in PVB/AVE NMs to achieve win-win effects. The hydrophobicity of PVB-AVE-6% was 120.9° whereas its filterability reached 98.3% when the pressure drop resistance was 142 Pa. PVB-AVE-6% exhibited intriguing properties with great antibacterial rates of 99.38% and 98.96% against S. aureus and E. coli, respectively. After a prolonged usability test of 8 h, the filtration efficiency of the PVB/AVE masks remained stable at over 97.7%. Furthermore, the antibacterial rates of the PVB/AVE masks on S. aureus and E. coli were 96.87% and 96.20% respectively, after using for 2 d. These results indicate that PVB/AVE NMs improve the protective performance of ordinary disposable masks, which has certain application in air filtration.

Antibody persistence and safety after heterologous boosting with orally aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously: 12-month analyses of a randomized controlled trial.

Antibody persistence and safety up to 12 months of heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose inactivated SARS-CoV-2 vaccine (CoronaVac) previously, has not been reported yet. This randomized, open-label, single-centre trial included Chinese adults who have received two-dose CoronaVac randomized to low-dose or high-dose aerosolised Ad5-nCoV group, or CoronaVac group. In this report, we mainly evaluated the geometric mean titres (GMTs) of neutralizing antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron BA.4/5 pseudovirus at 12 months after the booster dose and the incidence of serious adverse events (SAEs) till month 12. Of 419 participants, all were included in the safety analysis and 120 (28.64%) were included in the immunogenicity analysis. Serum NAb GMT against live wild-type SARS-CoV-2 was 204.36 (95% CI 152.91, 273.14) in the low-dose group and 171.38 (95% CI 121.27, 242.19) in the high-dose group at month 12, significantly higher than the GMT in the CoronaVac group (8.00 [95% CI 4.22, 15.17], p < 0.0001). Serum NAb GMT against omicron BA.4/5 pseudovirus was 40.97 (95% CI 30.15, 55.67) in the low-dose group and 35.08 (95% CI 26.31, 46.77) in the high-dose group at month 12, whereas the GMT in the CoronaVac group was below the lower limit of detection. No vaccine-related SAEs were observed. Orally administered aerosolised Ad5-nCoV following two-dose CoronaVac priming has a good safety profile and is persistently more immunogenic than three-dose CoronaVac within 12 months after the booster dose.Trial registration: ClinicalTrials.gov identifier: NCT05043259..

Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients: A Retrospective Observational Study.

OBJECTIVE: To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older. METHODS: This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression. RESULTS: Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19. CONCLUSION: The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19.

The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water solubility, we prioritized the GC376 scaffold as being optimal for optimization. We identified multiple drug-like compounds with <10 nM potency for inhibiting SARS-CoV-2 3CL and the ability to block SARS-CoV-2 replication in human cells, obtained co-crystal structures of the 3CL protease in complex with these compounds, and determined that they have pan-coronavirus activity. We selected one compound, termed coronastat, as an optimized lead and characterized it in pharmacokinetic and safety studies in vivo. Coronastat represents a new candidate for a small molecule protease inhibitor for the treatment of SARS-CoV-2 infection for eliminating pandemics involving coronaviruses.

How does working from home affect developer productivity? — A case study of Baidu during the COVID-19 pandemic

Nowadays, working from home (WFH) has become a popular work arrangement due to its many potential benefits for both companies and employees (e.g., increasing job satisfaction and retention of employees). Many previous studies have investigated the impact of WFH on the productivity of employees. However, most of these studies usually use a qualitative analysis method such as surveys and interviews, and the studied participants do not work from home for a long continuing time. Due to the outbreak of coronavirus disease 2019 (COVID-19), a large number of companies asked their employees to work from home, which provides us an opportunity to investigate whether WFH affects their productivity. In this study, to investigate the difference in developer productivity between WFH and working onsite, we conduct a quantitative analysis based on a dataset of developers’ daily activities from Baidu Inc., one of the largest IT companies in China. In total, we collected approximately four thousand records of 139 developers’ activities of 138 working days. Out of these records, 1103 records are submitted when developers work from home due to the COVID-19 pandemic. We find that WFH has both positive and negative impacts on developer productivity in terms of different metrics, e.g., the number of builds/commits/code reviews. We also notice that WFH has different impacts on projects with different characteristics including programming language, project type/age/size. For example, WFH has a negative impact on developer productivity for large projects. Additionally, we find that productivity varies for different developers. Based on these findings, we get some feedback from developers of Baidu and understand some reasons why WFH has different impacts on developer productivity. We also conclude several implications for both companies and developers.

The Spatial Effect of Shared Mobility on Urban Traffic Congestion: Evidence from Chinese Cities

This paper explores the spatial spillover effect of shared mobility on urban traffic congestion by constructing spatial econometric models. Based on panel data of 94 Chinese cities from 2016 to 2019, this study analyses the spatial correlation of shared mobility enterprise layout and geographical correlation of urban transport infrastructure and examines their influence mechanism. From the perspective of geographic spatial distribution, congestion has positive spatial correlation among Chinese cities, and it has different directions and centripetal forces across regions. The shared mobility enterprises in a region have same direction distribution with traffic congestion, but the centripetal forces of the aggregation effect are different. The econometric results include the fact that bike-sharing has reduced congestion significantly, but the overall impact of car-sharing is not clear. Neither bike-sharing nor car-sharing can offset the traffic congestion caused by economic activities and income growth. From the perspective of spillover effects, congestion has been influenced by bike-sharing, economic development, population, and public passengers in surrounding areas. In terms of spatial heterogeneity, bike-sharing relieves congestion in the Pearl River Delta region while having no significant effect in other regions. Meanwhile, car-sharing has aggravated congestion in the Yangtze River Delta but eased traffic jams in the Pearl River Delta.

Impact of near-surface turbulence on PM2.5 concentration in Chengdu during the COVID-19 pandemic.

The role of meteorological conditions has long been recognized in modulating regional air quality. The impact of near-surface turbulence, nevertheless, remains poorly understood. To curb the spread of COVID-19, a variety of lockdown measures were implemented, providing us an unprecedented opportunity to examine the joint impact of emission control and meteorology on regional air quality. Here we examined the variations of planetary boundary layer (PBL) height, PM2.5 concentrations, turbulence kinetic energy (TKE), vertical wind shear, and their associations in Chengdu, Sichuan province in Southwest China between January 13 and February 24, 2020, by synergistically using micro pulse lidar, ground-level meteorological and PM2.5 measurements, as well as ultrasonic anemometer observations. During the study period, Sichuan basin was primarily regulated by the straight west wind, with an averaged wind speed of 2-3 m/s at 850 hPa, indicative of a relatively stable atmospheric dispersion condition. TKE was positively correlated with PBL height but negatively correlated with PM2.5. The PM2.5 concentration varied dramatically during pre- and post-lockdown periods but remained near constant at a relatively low level during the lockdown period. Meanwhile, the negative correlation between TKE and PM2.5 was much stronger during the lockdown and post-lockdown periods, when aerosol emissions were significantly reduced. Moreover, the correlation between TKE and PM2.5 exhibited large diurnal variability, with the strongest correlation observed during the daytime when solar radiation and turbulent mixing generally reached their peaks. Overall, the observational results in Chengdu underscore the non-negligible impact of turbulence on regional PM2.5 concentrations, which could help better understand the variation of regional air pollution events.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

COVID-19: Opportunities for interdisciplinary research to improve care for older people in Sweden.

The emergence of COVID-19 has changed the world as we know it, arguably none more so than for older people. In Sweden, the majority of COVID-19-related fatalities have been among people aged ⩾70 years, many of whom were receiving health and social care services. The pandemic has illuminated aspects within the care continuum requiring evaluative research, such as decision-making processes, the structure and organisation of care, and interventions within the complex public-health system. This short communication highlights several key areas for future interdisciplinary and multi-sectorial collaboration to improve health and social care services in Sweden. It also underlines that a valid, reliable and experiential evidence base is the sine qua non for evaluative research and effective public-health systems.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma.

BACKGROUND: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. CASE PRESENTATION: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. CONCLUSION: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

COVID-19 information propagation dynamics in the Chinese Sina-microblog.

The outbreak of a novel coronavirus (COVID-19) generated an outbreak of public opinions in the Chinese Sina-microblog. To help in designing effective communication strategies during a major public health emergency, we propose a multiple-information susceptible-discussing-immune (M-SDI) model in order to understand the patterns of key information propagation on social networks. We develop the M-SDI model, based on the public discussion quantity and take into account of the behavior that users may re-enter another related topic or Weibo after discussing one. Data fitting using the real data of COVID-19 public opinion obtained from Chinese Sina-microblog can parameterize the model to make accurate prediction of the public opinion trend until the next major news item occurs. The reproduction ratio has fallen from 1.7769 and maintained around 0.97, which reflects the peak of public opinion has passed but it will continue for a period of time.