Clinical and immunological features of convalescent pediatric patients infected with the SARS-CoV-2 Omicron variant in Tianjin, China

COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain "Omicron", with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARS-CoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.

Systematic benchmarking of nanopore Q20+ kit in SARS-CoV-2 whole genome sequencing

Whole genome sequencing provides rapid insight into key information about the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), such as virus typing and key mutation site, and this information is important for precise prevention, control and tracing of coronavirus disease 2019 (COVID-19) outbreak in conjunction with the epidemiological information of the case. Nanopore sequencing is widely used around the world for its short sample-to-result time, simple experimental operation and long sequencing reads. However, because nanopore sequencing is a relatively new sequencing technology, many researchers still have doubts about its accuracy. The combination of the newly launched nanopore sequencing Q20+ kit (LSK112) and flow cell R10.4 is a qualitative improvement over the accuracy of the previous kits. In this study, we firstly used LSK112 kit with flow cell R10.4 to sequence the SARS-CoV-2 whole genome, and summarized the sequencing results of the combination of LSK112 kit and flow cell R10.4 for the 1200bp amplicons of SARS-CoV-2. We found that the proportion of sequences with an accuracy of more than 99% reached 30.1%, and the average sequence accuracy reached 98.34%, while the results of the original combination of LSK109 kit and flow cell R9.4.1 were 0.61% and 96.52%, respectively. The mutation site analysis showed that it was completely consistent with the final consensus sequence of next generation sequencing (NGS). The results showed that the combination of LSK112 kit and flow cell R10.4 allowed rapid whole-genome sequencing of SARS-CoV-2 without the need for verification of NGS.

Distribution and impacts on the geological environment of antiviral drugs in major waters of Wuhan, China

This study investigated water samples collected from the surface water and groundwater in Wuhan City, Hubei Province, China in different stages of the outbreak of the coronavirus disease 2019 (hereinafter referred to as COVID-19) in the city, aiming to determine the distribution characteristics of antiviral drugs in the city’s waters. The results are as follows. The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3. The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water. Two antiviral drugs and two glucocorticoids were detected in the surface water, groundwater, and sewage during the COVID-19 outbreak. Among them, chloroquine phosphate and cortisone had higher detection rates of 32.26% and 25.80%, respectively in all samples. The concentrations of residual drugs in East Lake were higher than those in other waters. The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate, whose detection rates in the surface water and the groundwater were 53.85% and 28.57%, respectively. Moreover, the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake. The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable. The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak, and they have not yet caused any negative impacts on the ecological environment.©2022 China Geology Editorial Office.

Global research trends on diseases in the elderly population: a visualization analysis (preprint)

Background Currently, populations around the world are rapidly ageing. Hence, the number of scientific publications on diseases in the elderly population (aged 60 and over) has been expanding.Objective This study aimed to use bibliometric analysis method to illustrate the global research trends over the past 20 years and to summarize the research hotspots that are likely to be addressed in future studies.Methods A literature search for medical publications on diseases in the elderly population in the period from 2000 to 2021 was conducted in the Web of Science Core Collection on April 20, 2022. Visualization analysis was performed using VOSviewer software (version 1.6.16).Results A total of 12,108 publications of the period from 2000 to 2021 were retrieved. The annual publication output grew gradually from 177 in 2000 to 1,236 in 2021. Articles (n = 10,264, 84.77%) were the most common type of documents. The USA issued the largest number of publications (n = 3,632, 30.00%) and had the most citations (citations = 141,230), with the United States Department of Health and Human Services making the largest contribution (n = 1,904, 15.73%). The Lancet had the most citations (citations = 28,548). A total of 545 meaningful topics were identified and further classified into 5 different clusters. The keywords ‘COVID-19’, ‘muscle mass’, ‘depression’ and ‘non-alcoholic fatty liver disease’ have drawn substantial attention in recent years, indicating that these areas will be the centre of attention in future studies on the elderly population.Conclusions This study provides an unbiased visualization analysis of this topic in a scale-efficient manner and includes directions for further research.

Both underweight and obesity are associated with an increased risk of corona virus disease 2019(COVID-19) severity (preprint)

Background: As COVID-19 evolved into a global pandemic. Increasing numbers of reports have linked obesity to more severe COVID-19 illness and death (1-3). However, almost all the studies focused on the proportion of people entering the ICU or mortality. Is obesity also associated with severity of pneumonia in common pneumonia patients? How about underweight patients? The answer is lack. So, our research below will answer the question. Methods: We collected and analyzed epidemiological, demographic, clinical, and laboratory data from 193 confirmed cases of COVID-19 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, between January 1, 2020, and March 13, 2020. They were followed up until April 15, 2020. Results: Among these patients, 5.70% were underweight, 58.03% were normal weight, 27.98% were overweight and 8.29% were obese. underweight patients were more likely to have headache (P=0.029) Obese patients were more likely to experience a decline in lymphocyte counts(P=0.042), an increase in CRP(P=0.020), bilateral multiple mottling and groundglass opacity (P=0.008). Besides, the proportion of patients receiving human immunoglobulin+systematic corticosteroids treatment is the highest among the obese group compared with other BMI groups. After adjusting for potential confounders, Underweight patients had 6.483-fold higher(P=0.012)，and obesity patients showed 5.965-fold higher odds developing acute lung injury(ALI) than normal weight patients(P=0.022). Underweight patients were 3.255 times more likely than normal-weight patients to develop secondary infections (P=0.041). Conclusions: Our study shows that in patients with common pneumonia, both underweight and obese people tend to develop ALI compared with normal weight patients.

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.

The Report on China-Spain Joint Clinical Testing for Rapid COVID-19 Risk Screening by Eye-region Manifestations (preprint)

BackgroundThe worldwide surge in coronavirus cases has led to the COVID-19 testing demand surge. Rapid, accurate, and cost-effective COVID-19 screening tests working at a population level are in imperative demand globally. MethodsBased on the eye symptoms of COVID-19, we developed and tested a COVID-19 rapid prescreening model using the eye-region images captured in China and Spain with cellphone cameras. The convolutional neural networks (CNNs)-based model was trained on these eye images to complete binary classification task of identifying the COVID-19 cases. The performance was measured using area under receiver-operating-characteristic curve (AUC), sensitivity, specificity, accuracy, and F1. The application programming interface was open access. FindingsThe multicenter study included 2436 pictures corresponding to 657 subjects (155 COVID-19 infection, 23{middle dot}6%) in development dataset (train and validation) and 2138 pictures corresponding to 478 subjects (64 COVID-19 infections, 13{middle dot}4%) in test dataset. The image-level performance of COVID-19 prescreening model in the China-Spain multicenter study achieved an AUC of 0{middle dot}913 (95% CI, 0{middle dot}898-0{middle dot}927), with a sensitivity of 0{middle dot}695 (95% CI, 0{middle dot}643-0{middle dot}748), a specificity of 0{middle dot}904 (95% CI, 0{middle dot}891 -0{middle dot}919), an accuracy of 0{middle dot}875(0{middle dot}861-0{middle dot}889), and a F1 of 0{middle dot}611(0{middle dot}568-0{middle dot}655). InterpretationThe CNN-based model for COVID-19 rapid prescreening has reliable specificity and sensitivity. This system provides a low-cost, fully self-performed, non-invasive, real-time feedback solution for continuous surveillance and large-scale rapid prescreening for COVID-19. FundingThis project is supported by Aimomics (Shanghai) Intelligent

The Report on China-Spain Joint Clinical Testing for Rapid COVID-19 Risk Screening by Eye-region Manifestations (preprint)

Background: The worldwide surge in coronavirus cases has led to the COVID-19 testing demand surge. Rapid, accurate, and cost-effective COVID-19 screening tests working at a population level are in imperative demand globally. Methods: Based on the eye symptoms of COVID-19, we developed and tested a COVID-19 rapid prescreening model using the eye-region images captured in China and Spain with cellphone cameras. The convolutional neural networks (CNNs)-based model was trained on these eye images to complete binary classification task of identifying the COVID-19 cases. The performance was measured using area under receiver-operating-characteristic curve (AUC), sensitivity, specificity, accuracy, and F1. The application programming interface was open access. Findings: The multicenter study included 2436 pictures corresponding to 657 subjects (155 COVID-19 infection, 23.6%) in development dataset (train and validation) and 2138 pictures corresponding to 478 subjects (64 COVID-19 infections, 13.4%) in test dataset. The image-level performance of COVID-19 prescreening model in the China-Spain multicenter study achieved an AUC of 0.913 (95% CI, 0.898-0.927), with a sensitivity of 0.695 (95% CI, 0.643-0.748), a specificity of 0.904 (95% CI, 0.891 -0.919), an accuracy of 0.875(0.861-0.889), and a F1 of 0.611(0.568-0.655). Interpretation: The CNN-based model for COVID-19 rapid prescreening has reliable specificity and sensitivity. This system provides a low-cost, fully self-performed, non-invasive, real-time feedback solution for continuous surveillance and large-scale rapid prescreening for COVID-19. Funding: This project is supported by Aimomics (Shanghai) Intelligent

Report on Three Round COVID-19 Risk Blind Tests by Screening Eye-region Manifestations (preprint)

The Coronavirus disease 2019 (COVID-19) has affected several million people since 2019. Despite various vaccines of COVID-19 protect million people in many countries, the worldwide situations of more the asymptomatic and mutated strain discovered are urging the more sensitive COVID-19 testing in this turnaround time. Unfortunately, it is still nontrivial to develop a new fast COVID-19 screening method with the easier access and lower cost, due to the technical and cost limitations of the current testing methods in the medical resource-poor districts. On the other hand, there are more and more ocular manifestations that have been reported in the COVID-19 patients as growing clinical evidence[1]. This inspired this project. We have conducted the joint clinical research since January 2021 at the ShiJiaZhuang City, Heibei province, China, which approved by the ethics committee of The fifth hospital of ShiJiaZhuang of Hebei Medical University. We undertake several blind tests of COVID-19 patients by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Meantime as an important part of the ongoing globally COVID-19 eye test program by AIMOMICS since February 2020, we propose a new fast screening method of analyzing the eye-region images, captured by common CCD and CMOS cameras. This could reliably make a rapid risk screening of COVID-19 with the sustainable stable high performance in different countries and races. For this clinical trial in ShiJiaZhuang, we compare and analyze 1194 eye-region images of 115 patients, including 66 COVID-19 positive patients, 44 rehabilitation patients (nucleic acid changed from positive to negative), 5 liver patients, as well as 117 healthy people. Remarkably, we consistently achieved very high testing results (> 0.94) in terms of both sensitivity and specificity in our blind test of COVID-19 patients. This confirms the viability of the COVID-19 fast screening by the eye-region manifestations. Particularly and impressively, the results have the similar conclusion as the other clinical trials of the globally COVID-19 eye test program[1]. Hopefully, this series of ongoing globally COVID-19 eye test study, and potential rapid solution of fully self-performed COVID risk screening method, can be inspiring and helpful to more researchers in the world soon. Our model for COVID-19 rapid prescreening have the merits of the lower cost, fully self-performed, non-invasive, importantly real-time, and thus enables the continuous health surveillance. We further implement it as the open accessible APIs, and provide public service to the world. Our pilot experiments show that our model is ready to be usable to all kinds of surveillance scenarios, such as infrared temperature measurement device at airports and stations, or directly pushing to the target people groups smartphones as a packaged application.

Rapid COVID-19 Risk Screening by Eye-region Manifestations (preprint)

It is still nontrivial to develop a new fast COVID-19 screening method with the easier access and lower cost, due to the technical and cost limitations of the current testing methods in the medical resource-poor districts. On the other hand, there are more and more ocular manifestations that have been reported in the COVID-19 patients as growing clinical evidence[1]. This inspired this project. We have conducted the joint clinical research since January 2021 at the ShiJiaZhuang City, Heibei province, China, which approved by the ethics committee of The fifth hospital of ShiJiaZhuang of Hebei Medical University. We undertake several blind tests of COVID-19 patients by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Meantime as an important part of the ongoing globally COVID-19 eye test program by AIMOMICS since February 2020, we propose a new fast screening method of analyzing the eye-region images, captured by common CCD and CMOS cameras. This could reliably make a rapid risk screening of COVID-19 with the sustainable stable high performance in different countries and races. Our model for COVID-19 rapid prescreening have the merits of the lower cost, fully self-performed, non-invasive, importantly real-time, and thus enables the continuous health surveillance. We further implement it as the open accessible APIs, and provide public service to the world. Our pilot experiments show that our model is ready to be usable to all kinds of surveillance scenarios, such as infrared temperature measurement device at airports and stations, or directly pushing to the target people groups smartphones as a packaged application.

The epidemiological characteristics and effectiveness of countermeasures to contain coronavirus disease 2019 in Ningbo City, Zhejiang Province, China.

A novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible-exposed-infectious-asymptomatic-recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher's Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ2 = 0.052, P = 0.819) by Kruskal-Wallis test. The effective reproduction number (Reff) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China.

Transmission of SARS-CoV-2 in Public Transportation Vehicles: A Case Study in Hunan Province, China.

Here we report a case study of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak event during bus trips of an index patient in Hunan Province, China. This retrospective investigation suggests potential airborne transmission of SARS-CoV-2 and the possibility of superspreading events in certain close contact and closed space settings, which should be taken into account when control strategies are planned.

A five-compartment model of age-specific transmissibility of SARS-CoV-2.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also called 2019-nCoV) causes different morbidity risks to individuals in different age groups. This study attempts to quantify the age-specific transmissibility using a mathematical model. METHODS: An epidemiological model with five compartments (susceptible-exposed-symptomatic-asymptomatic-recovered/removed [SEIAR]) was developed based on observed transmission features. Coronavirus disease 2019 (COVID-19) cases were divided into four age groups: group 1, those ≤ 14 years old; group 2, those 15 to 44 years old; group 3, those 45 to 64 years old; and group 4, those ≥ 65 years old. The model was initially based on cases (including imported cases and secondary cases) collected in Hunan Province from January 5 to February 19, 2020. Another dataset, from Jilin Province, was used to test the model. RESULTS: The age-specific SEIAR model fitted the data well in each age group (P < 0.001). In Hunan Province, the highest transmissibility was from age group 4 to 3 (median: ß43 = 7.71 × 10- 9; SAR43 = 3.86 × 10- 8), followed by group 3 to 4 (median: ß34 = 3.07 × 10- 9; SAR34 = 1.53 × 10- 8), group 2 to 2 (median: ß22 = 1.24 × 10- 9; SAR22 = 6.21 × 10- 9), and group 3 to 1 (median: ß31 = 4.10 × 10- 10; SAR31 = 2.08 × 10- 9). The lowest transmissibility was from age group 3 to 3 (median: ß33 = 1.64 × 10- 19; SAR33 = 8.19 × 10- 19), followed by group 4 to 4 (median: ß44 = 3.66 × 10- 17; SAR44 = 1.83 × 10- 16), group 3 to 2 (median: ß32 = 1.21 × 10- 16; SAR32 = 6.06 × 10- 16), and group 1 to 4 (median: ß14 = 7.20 × 10- 14; SAR14 = 3.60 × 10- 13). In Jilin Province, the highest transmissibility occurred from age group 4 to 4 (median: ß43 = 4.27 × 10- 8; SAR43 = 2.13 × 10- 7), followed by group 3 to 4 (median: ß34 = 1.81 × 10- 8; SAR34 = 9.03 × 10- 8). CONCLUSIONS: SARS-CoV-2 exhibits high transmissibility between middle-aged (45 to 64 years old) and elderly (≥ 65 years old) people. Children (≤ 14 years old) have very low susceptibility to COVID-19. This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

The immunodominant and neutralization linear epitopes for SARS-CoV-2 (preprint)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induced antibody production, six of which were immunodominant epitopes in patients identified via the binding of epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the immunodominant epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.

The prevalence of antibodies to SARS-CoV-2 among blood donors in China (preprint)

Objectives The prevalence of antibodies to SARS-CoV-2 among blood donors in China remains unknown. To reveal the missing information, we investigated the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang of China. Design Cross-sectional study Setting Three blood centers, located in the central, south and north China, respectively, recruiting from January to April 2020. Participants 38,144 healthy blood donors donated in Wuhan, Shenzhen and Shijiazhuang were enrolled, who were all met the criteria for blood donation during the COVID-19 pandemic in China. Main outcome measures Specific antibodies against SARS-CoV-2 including total antibody (TAb), IgG antibody against receptor-binding domain of spike protein (IgG-RBD) and nucleoprotein (IgG-N), and IgM. Pseudotype lentivirus-based neutralization test was performed on all TAb-positive samples. In addition, anonymous personal demographic information, including gender, age, ethnicity, occupation and educational level, and blood type were collected. Results A total of 519 samples from 410 donors were confirmed by neutralization tests. The SARS-CoV-2 seroprevalence among blood donors was 2.29% (407/17,794, 95%CI: 2.08% to 2.52%) in Wuhan, 0.029% (2/6,810, 95%CI: 0.0081% to 0.11%) in Shenzhen, and 0.0074% (1/13,540, 95%CI: 0.0013% to 0.042%) in Shijiazhuang, respectively. The earliest emergence of SARS-CoV-2 seropositivity in blood donors was identified on January 20, 2020 in Wuhan. The weekly prevalence of SARS-CoV-2 antibodies in Wuhan's blood donors changed dynamically and were 0.08% (95%CI: 0.02% to 0.28%) during January 15 to 22 (before city lockdown), 3.08% (95%CI: 2.67% to 3.55%) during January 23 to April 7 (city quarantine period) and 2.33% (95%CI: 2.06% to 2.63%) during April 8 to 30 (after lockdown easing). Female and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among donors in Wuhan. Conclusions The prevalence of antibodies to SARS-CoV-2 among blood donors in China was low, even in Wuhan city. According to our data, the earliest emergence of SARS-CoV-2 in Wuhan's donors should not earlier than January, 2020. As most of the population of China remained uninfected during the early wave of COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.

COVID-19: Effects of weather conditions on the propagation of respiratory droplets (preprint)

As the number of confirmed cases of Coronavirus disease 2019 (COVID-19) continues to increase, there has been a rising concern regarding the effect of weather conditions, especially over the upcoming summer, on the transmission of this disease. In this study, we assess the transmission of COVID-19 under different weather conditions by investigating the propagation of infectious respiratory droplets. A comprehensive mathematical model is established to explore their evaporation, heat transfer and kinematics under different temperature, humidity and ventilation conditions. The transmitting pathway of COVID-19 through respiratory droplets is divided into short-range droplet contacts and long-range aerosol exposure. We show that the effect of weather conditions is not monotonic: low temperature and high humidity facilitate droplet contact transmission, while high temperature and low humidity promote the formation of aerosol particles and accumulation of particles with a diameter of 2.5 m or less (PM2.5). Our model suggests that the 6 ft of social distance recommended by the Center for Disease Control and Prevention (CDC) may be insufficient in certain environmental conditions, as the droplet spreading distance can be as long as 6 m (19.7 ft) in cold and humid weather. The results of this study suggest that the current pandemic may not ebb in the summer of the northern hemisphere without proper intervention, as there is an increasing chance of aerosol transmission. We also emphasize that the meticulous design of building ventilation systems is critical in containing both the droplet contact infections and aerosol exposures.

Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis (preprint)

The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection.

Aveolar Macrophage Activation and Cytokine Storm in the Pathogenesis of Severe COVID-19 (preprint)

The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.