Two fitness inference schemes compared using allele frequencies from 1,068,391 sequences sampled in the UK during the COVID-19 pandemic (preprint)

Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e., as to which sequences observed that week are most fit. We also find that agreement between ranking of sequences varies with genetic unimodality in the population in a given week.

Exploring year-to-year changes in station-based bike sharing commuter behaviors with smart card data

Station-based bike sharing (SBBS) not only provides commuters with direct "door-to-door" trips, but also plays a vital role in addressing the "first/last mile" challenges for public transportation system. However, there is a lack of research into portraying year-to-year changes in SBBS commuter behaviors. With five-year (from 2016 to 2020) SBBS smart card data collected in Nanjing, China, a longitudinal analysis is performed in this study to trace yearly dynamics of commuter behaviors at an individual level. We identify two sorts of SBBS commuters (i.e., SBBS-alone and SBBS-metro commuters) based on users' spatial-temporal travel regularities. The paper finds that (i) the number of SBBS users presented a considerable fluctuation trend over a five-year span, while the proportion of SBBS commuters stabilized at an equilibrium level;(ii) the COVID-19 outbreak accelerated the decline in the proportion of female and young SBBS commuters;(iii) most SBBS commuters were recorded for only one year out of five, while the share of commuters who used SBBS for four years or more is tiny, < 5%;(iv) the trip duration of SBBS-alone commuters was significantly longer than that of SBBS-metro commuters, and both showed some increase during the COVID-19 pandemic;(v) the number of non-loop trip chains was dramatically higher than that of loop trip chains, which is more prominent among SBBS-metro commuters. Our findings could provide valuable insights into the behavioral dynamics of SBBS commuters and offer recommendations on how policy makers and transportation planners could respond to these precipitate changes. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

DNA damage contributes to age-associated differences in SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and hampered by inhibition of the DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of angiotensin-converting enzyme 2 (ACE2), the primary receptor of SARS-CoV-2, by activation of transcription factor c-Jun. Importantly, in vivo experiment using a mouse-adapted viral strain also verified the significant roles of DNA damage in viral entry and severity of infection. Expression of ACE2 was elevated in the older human and mice tissues and positively correlated with γH2AX, a DNA damage biomarker, and phosphorylated c-Jun (p-c-Jun). Finally, nicotinamide mononucleotide (NMN) and MDL-800, which promote DNA repair, alleviated SARS-CoV-2 infection and disease severity in vitro and in vivo. Taken together, our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel approach for antiviral intervention.

Effects of enhanced hygiene measures on severe diarrhea and anastomotic leak after colorectal cancer surgery: the experience of a tertiary referral hospital in China.

Background: The 2019 novel coronavirus (COVID-19) global pandemic has greatly changed the mode of hospital admissions. This study summarized and analyzed the incidence of severe diarrhea and anastomotic leakage during different periods for colorectal cancer surgery. Methods: From January 2017 to September 2020, 2,619 colorectal operations were performed in Peking Union Medical College Hospital. In contrast with previous years, enhanced hand hygiene training, more frequent ventilation of the wards, and separate bed treatments for patients were implemented in 2020. Data on incidence of severe diarrhea and anastomotic leakage were retrieved and collected. Results: The number of cases of severe diarrhea after colorectal surgery was 32 (4.60%), 24 (3.33%), 32 (3.83%), and 11 (2.99%) in 2017, 2018, 2019, and 2020 respectively, while the incidence of anastomotic leakage was 3.30% (23/696), 3.75% (27/720), 2.87% (24/835), and 2.17% (8/368), respectively. There was no significant difference in the incidence of postoperative severe diarrhea or anastomotic leakage across the various years. Conclusions: The number of colorectal surgeries in 2020 was significantly decreased due to the COVID-19 pandemic. Among the different years, no difference was observed regarding the incidence of postoperative flora disorder or anastomosis leakage. Enhanced hygiene measures during the COVID-19 epidemic partially contributed to the decrease of severe diarrhea and anastomotic leakage.

Association of delayed chemoradiotherapy with elevated Epstein-Barr virus DNA load and adverse clinical outcome in nasopharyngeal carcinoma treatment during the COVID-19 pandemic: a retrospective study.

BACKGROUND: To summarize the impact of radiotherapy (RT) and chemotherapy delays on patients with nasopharyngeal carcinoma (NPC) during the COVID-19 pandemic. METHODS: We retrospectively included 233 patients with stage II-IVa NPC treated with RT and chemotherapy between December 11, 2019 and March 11, 2020. The outcomes were elevation in the EBV DNA load between two adjacent cycles of chemotherapy or during RT, and 1-year disease-free survival (DFS). RESULTS: RT delay occurred in 117 (50%) patients, and chemotherapy delay occurred in 220 (94%) patients. RT delay of ≥ 6 days was associated with a higher EBV DNA elevation rate (20.4% vs. 3.6%, odds ratio [OR] = 6.93 [95% CI = 2.49-19.32], P < 0.001), and worse 1-year DFS (91.2% vs. 97.8%, HR = 3.61 [95% CI = 1.37-9.50], P = 0.006), compared with on-schedule RT or delay of < 6 days. Chemotherapy delay of ≥ 10 days was not associated with a higher EBV DNA elevation rate (12.5% vs. 6.8%, OR = 1.94 [95% CI = 0.70-5.40], P = 0.20), or worse 1-year DFS (93.8% vs. 97.1%, HR = 3.73 [95% CI = 0.86-16.14], P = 0.059), compared with delay of < 10 days. Multivariable analyses showed RT delay of ≥ 6 days remained an independent adverse factor for both EBV DNA elevation and DFS. CONCLUSION: To ensure treatment efficacy for patients with nonmetastatic NPC, initiation of RT should not be delayed by more than 6 days; the effect of chemotherapy delay requires further investigation.

National emissions inventory and future trends in greenhouse gases and other air pollutants from civil airports in China.

Civil aviation is an important source of air pollutants, but this field has received insufficient attention in China. Based on the standard emissions model of the International Civil Aviation Organization (ICAO) and actual flight information from 241 airports, this study estimated a comprehensive emissions inventory for 2010-2020 by considering the impacts of mixing layer height. The results showed that annual pollutant emissions rapidly trended upward along with population and economic growth; however, the emissions decreased owing to the impacts of the COVID-19 pandemic. In 2020, the emissions of carbon monoxide (CO), nitrogen oxides (NOX), particulate matter (PM), methane (CH4), nitrous oxide (N2O), carbon dioxide (CO2), and water vapor (H2O) were 34.34, 65.73, 0.10, 0.34, 0.40, 14,706.26, and 5733.11 Gg, respectively. The emissions of total volatile organic compounds (VOCs) from China's civil airports in 2020 were estimated at 17.20 Gg; the major components were formic acid (1.70 Gg), acetic acid (1.62 Gg), 1-butylene (1.03 Gg), acetone (0.96 Gg), and acetaldehyde (0.93 Gg). The distribution of pollutant emissions was consistent with the level of economic development, mainly in Beijing, Guangzhou, and Shanghai. In addition, we estimated future pollution trends for the aviation industry under four scenarios. Under the comprehensive scenario, which considered the impacts of economic growth, passenger turnover, cargo turnover, COVID-19, and technological efficiency, the levels of typical pollutants were expected to increase by nearly 1.51-fold from 2010 to 2035.

Exploring year-to-year changes in station-based bike sharing commuter behaviors with smart card data

Station-based bike sharing (SBBS) not only provides commuters with direct “door-to-door” trips, but also plays a vital role in addressing the “first/last mile” challenges for public transportation system. However, there is a lack of research into portraying year-to-year changes in SBBS commuter behaviors. With five-year (from 2016 to 2020) SBBS smart card data collected in Nanjing, China, a longitudinal analysis is performed in this study to trace yearly dynamics of commuter behaviors at an individual level. We identify two sorts of SBBS commuters (i.e., SBBS-alone and SBBS-metro commuters) based on users’ spatial-temporal travel regularities. The paper finds that (i) the number of SBBS users presented a considerable fluctuation trend over a five-year span, while the proportion of SBBS commuters stabilized at an equilibrium level;(ii) the COVID-19 outbreak accelerated the decline in the proportion of female and young SBBS commuters;(iii) most SBBS commuters were recorded for only one year out of five, while the share of commuters who used SBBS for four years or more is tiny, <5%;(iv) the trip duration of SBBS-alone commuters was significantly longer than that of SBBS-metro commuters, and both showed some increase during the COVID-19 pandemic;(v) the number of non-loop trip chains was dramatically higher than that of loop trip chains, which is more prominent among SBBS-metro commuters. Our findings could provide valuable insights into the behavioral dynamics of SBBS commuters and offer recommendations on how policy makers and transportation planners could respond to these precipitate changes.

The optimal vaccination strategy to control COVID-19: a modeling study in Wuhan City, China.

BACKGROUND: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. METHODS: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (Reff) was used to estimate the transmission interaction in different age groups. RESULTS: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (Reff = 4.28), followed by group 2 to 3 (Reff = 2.61), and group 2 to 4 (Reff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old. CONCLUSIONS: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China.

A network meta-analysis of secondary attack rates of COVID-19 in different contact environments.

As the corona virus disease 2019 (COVID-19) pandemic continues around the world, understanding the transmission characteristics of COVID-19 is vital for prevention and control. We conducted the first study aiming to estimate and compare the relative risk of secondary attack rates (SARs) of COVID-19 in different contact environments. Until 26 July 2021, epidemiological studies and cluster epidemic reports of COVID-19 were retrieved from SCI, Embase, PubMed, CNKI, Wanfang and CBM in English and Chinese, respectively. Relative risks (RRs) were estimated in pairwise comparisons of SARs between different contact environments using the frequentist NMA framework, and the ranking of risks in these environments was calculated using the surface under the cumulative ranking curve (SUCRA). Subgroup analysis was performed by regions. Thirty-two studies with 68 260 participants were identified. Compared with meal or gathering, transportation (RR 10.55, 95% confidence interval (CI) 1.43-77.85), medical care (RR 11.68, 95% CI 1.58-86.61) and work or study places (RR 10.15, 95% CI 1.40-73.38) had lower risk ratios for SARs. Overall, the SUCRA rankings from the highest to the lowest were household (95.3%), meal or gathering (81.4%), public places (58.9%), daily conversation (50.1%), transportation (30.8%), medical care (18.2%) and work or study places (15.3%). Household SARs were significantly higher than other environments in the subgroup of mainland China and sensitive analysis without small sample studies (<100). In light of the risks, stratified personal protection and public health measures need to be in place accordingly, so as close contacts categorising and management.

Should bike-sharing continue operating during the COVID-19 pandemic? Empirical findings from Nanjing, China.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has triggered a worldwide outbreak of pandemic, and transportation services have played a key role in coronavirus transmission. Although not crowded in a confined space like a bus or a metro car, bike-sharing users are exposed to the bike surface and take the transmission risk. During the COVID-19 pandemic, how to meet user demand and avoid virus spreading has become an important issue for bike-sharing. METHODS: Based on the trip data of bike-sharing in Nanjing, China, this study analyzes the travel demand and operation management before and after the pandemic outbreak from the perspectives of stations, users, and bikes. Semi-logarithmic difference-in-differences model, visualization methods, and statistic indexes are applied to explore the transportation service and risk prevention of bike-sharing during the pandemic. RESULTS: Pandemic control strategies sharply reduced user demand, and commuting trips decreased more significantly. Some stations around health and religious places become more important. Men and older adults may be more dependent on bike-sharing systems. The declined trips reduce user contacts and transmission risk. Central urban areas have more user close contacts and higher transmission risk than suburban areas. Besides, a new concept of user distancing is proposed to decrease transmission risk and the number of idle bikes. CONCLUSIONS: This paper is the first research focusing on both user demand and transmission risk of bike-sharing during the COVID-19 pandemic. This study evaluates the mobility role of bike-sharing during the COVID-19 pandemic, and also provides insights into curbing the viral transmission within the city.

Exploring the relationship between the COVID-19 pandemic and changes in travel behaviour: A qualitative study.

During the COVID-19 crisis, a series of measures were taken to restrict travel and social activities outside the home in order to curb the pandemic and ameliorate its negative effects. These unprecedented measures have had a profound impact on the number and purposes of trips and modes of travel. In China, although the pandemic is now generally under control and transport availability has returned to nearly normal, the extent of the changes in travel behaviour wrought during and after the pandemic still remains unclear. Therefore, the aim of this paper is to investigate the differences in individual travel behaviours during and after the COVID-19 pandemic, using Huzhou as an example. Semi-structured interviews were used to examine the influence of COVID-19 on the travel behaviour and perceptions of different groups. The results indicate that, initially, travel demand was greatly reduced. Second, decreased travel reduced participation in activities, which can have adverse effects on people's health as well as their subjective well-being. Third, the degree and duration of such impacts varied from person to person. Students, lower income cohorts, groups living in small communities with insufficient green spaces, and those working in tourism, catering, informal businesses and transport-related sectors were more vulnerable than others. Policymakers, urban and transport planners should therefore pay attention to the social inequities that arise from unequal access to transport and heterogeneity between individuals. Additionally, public transport systems require further development to promote social cohesion.

Development of Multivalent Nanobodies Blocking SARS CoV 2 Infection by Targeting RBD of Spike Protein (preprint)

Background: The outbreak and pandemic of coronavirus SARS CoV 2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS CoV 2 spike interaction with ACE2 protein were developed.Results: Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91 hFc and Nb3 hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91 Nb3 hFc exhibited the strongest RBD binding affinity and neutralizing ability against SARS CoV 2 pseudoviruses with an IC50 value at approximately 1.54 nM. Conclusions: The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91 Nb3 hFc may serve as a potential therapeutic agent for the treatment of COVID 19.

Little Risk of the COVID-19 Resurgence on Students in China (outside Hubei) Caused by School Reopening (preprint)

Objective: School reopening has not yet started in China where the COVID-19 outbreak has reached ending stage, largely due to a great concern about COVID-19 infections on students. We attempted to quantitatively evaluate the risk of COVID-19 infections on students caused by school reopening. Study design: We collected the data of the numbers of teachers, population size and newly confirmed COVID-19 cases in the past 14 days in typical provinces/cities of China, and then analyzed the risk of COVID-19 infections in schools with respect to each province/city. Methods: A step-by-step procedure was explored to calculate the probability of COVID-19 infections on students as transmitted from infected teachers. Two critical assumptions for analysis were proposed: (i) only locally generated cases were counted while imported cases were omitted; (ii) the secondary attack rate of the COVID-19 virus in schools is similar to that in households in China, ranging from 3-10%. Results: The probability of COVID-19 resurgence within one week on students of primary, middle and high schools in China (outside Hubei) is extremely low (<0.2%) in each province/city, and such probability can be updated daily and weekly based on the newly confirmed cases in the past 14 days. In some areas without newly confirmed cases in the past 14 days, the risk is zero. Conclusions: Our work provides guidance for local governments to make risk level-based policies for school reopening. Currently, the risk of COVID-19 infections on students is extremely low in China (outside Hubei) and therefore school reopening can be initiated without the endanger of infections on students.

Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources (preprint)

We report that COVID-19 mortality and recovery rates in Hubei Province, China exponentially decays (R2>0.93) and grows (R2>0.95), respectively. A great number of newly supplied medical resources (health workers and beds) enabled overwhelming patients to be treated effectively. This may help other countries to deal with the coming COVID-19 outbreaks.

Forecasting the Cumulative Number of COVID-19 Deaths in China: Can More Lives Be Saved? (preprint)

The COVID-19 outbreak is on-going in China. Here we estimated the potential total numbers of COVID-19 deaths in China, outside Hubei (in China), Hubei Province, Wuhan City and outside Wuhan (in Hubei) by Boltzmann function-based analyses, which are 3342 (95% CI, 3214, 3527), 111 (109, 114), 3245 (3100, 3423), 2613 (2498, 2767) and 627 (603, 654), respectively. The results may help to evaluate the severity of COVID-19 outbreaks and facilitate timely mental service for the families of passed patients.