Counterfactual time series analysis for the air pollution during the outbreak of COVID-19 in Wuhan (preprint)

Environmental issues are becoming one of the main topics of concern for society, and the quality of air is closely linked to people's lives. Previous studies have examined the effects of abrupt interventions on changes in air pollution. For example, researchers used an interrupted time series design to quantify the impact of the 1990 Dublin coal ban; and a regression discontinuity to determine the arbitrary spatial impact of the Huaihe River policy in China. An important feature of each of these studies is that they investigated abrupt and localized changes over relatively short time spans (the Dublin coal ban) and spatial scales (the Huaihe policy). Due to the abrupt nature of these interventions, defining a hypothetical experiment in these studies is straightforward. In response to the novel coronavirus outbreak, China implemented 'the largest quarantine in human history' in Wuhan on January 23, 2020. Similar measures were implemented in other Chinese cities. Since then, the movement of people and associated production and consumption activities have been significantly reduced. This provides us with an unprecedented opportunity to estimate the changes in air pollution brought about by this sudden "silent" move. We speculate that the initiative will lead to a significant reduction in regional air pollution. Thus, we performed counterfactual time series analysis on Wuhan air quality data from 2017-2022 based on three models, SARIMA, LSTM and XGBOOST, and compared the excellence of different models. Finally, we conclude that 'silent' measures will significantly reduce air pollution. Using this conclusion to further investigate the extent of air pollution reduction will help the country to better designate environmental policies.

Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.

COVID-19 vaccine uptake, reasons, and associated factors among older adults in Shenzhen, China.

Evidence is limited on the actual uptake of the coronavirus disease 2019 (COVID-19) vaccine among older adults, especially those with chronic diseases, during the pandemic. To examine COVID-19 vaccine uptake, reasons, and associated factor among older adults, a cross-sectional survey was conducted between September 24 and October 20, 2021 among older adults aged 60 and above in Shenzhen, China. Logistic regression analysis was used to examine associations of COVID-19 vaccine uptake with sociodemographic characteristics, pneumonia vaccination history, and participation in health education activities among older adults and among those with chronic diseases. Of the 951 participants, 82.8% reported being vaccinated against COVID-19 during the study period, but this proportion was relatively lower among adults aged 80 and above (62.7%) and those with chronic diseases (77.9%). The top-rated reasons for not being vaccinated included doctors not recommending it due to underlying diseases (34.1%), not being ready for it (18.3%), and failure to make an appointment (9.1%). General older adults who were aged below 70, had a high school and above education, were permanent residents of Shenzhen, were with good health and had pneumonia vaccination history were more likely to take the COVID-19 vaccination. Yet, among older adults with chronic diseases, other than age and permanent residency status, health status was the only significant indicator of COVID-19 vaccine uptake. Our study added to evidence that health condition is the critical barrier to the actual uptake of the COVID-19 vaccine among Chinese older adults, especially those aged 80 and above and those with chronic diseases.

SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19.

Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants.

Effect of Lockdown and Mass Testing for the SARS-CoV-2 Omicron Epidemic on Reducing New Infections in Shenzhen, China.

On 14 March 2022, China's tech hub Shenzhen, a mega-city with more than 18 million inhabitants, imposed a one-week citywide lockdown immediately after it observed a surge in infections. We assessed the effect of this one-week lockdown, coupled with mass testing, on reducing the daily number of new confirmed cases and asymptomatic cases during the Omicron wave, using an interrupted time series analysis approach. Our analysis suggests that the one-week citywide lockdown in Shenzhen was effective at lowering both daily new confirmed cases and asymptomatic cases during the Omicron wave. Early detection ensures timely isolation and treatment of infected patients in designated hospitals, and therefore helps lower the prevalence of confirmed cases and asymptomatic cases. Our findings of the immediate increase in asymptomatic cases after lockdown warrant further verifications in other city epidemic scenarios.

How does academia respond to the burden of infectious and parasitic disease?

BACKGROUND: Academic research is one of the main avenues through which humans can fight the threat of infectious diseases. However, there have been concerns regarding whether the academic system has provided sufficient efforts to fight infectious diseases we potentially face. Answering these questions could contribute to evidence-based recommendations for setting research priorities and third-mission policies. METHODS: With a focus on one of the most common categories of communicable diseases, infectious and parasitic diseases (IPDs), we searched Web of Science for articles and reviews relevant to IPDs published during the period 2000-2019 and retrieved WHO data on disease burden in corresponding years. The academic response patterns were explored by IPD subcategory and by human development level (an index established by the United Nations). We conduct the analysis in particular to gain insight into the dynamic relationship between disease burden and research effort on IPDs, scientific efforts contributed by countries with different development levels, and the variation trends in international joint efforts. RESULTS: The greatest burden of IPDs is clustered in the developing regions of Africa, but has received academic response from both developed and developing countries. Highly developed countries dominate the ranks of academic research in this area, yet there is also a clear increase in research efforts from the countries most affected, despite their low human development scale. In fact, the overall analysis reveals an improved capability for addressing local problems from African regions. In terms of international collaboration, highly developed countries such as the United States and United Kingdom have commonly collaborated with needy regions, whereas prolific but developing nations, like China, have not. CONCLUSIONS: From a global perspective, academia has positively responded to health needs caused by IPDs. Although the relevant research output contribution is primarily from the highly developed countries, concentrated and specialized efforts from the undeveloped regions to ease their local burden can be clearly observed. Our findings also indicate a tendency to focus more on local health needs for both developed and undeveloped regions. The insights revealed in this study should benefit a more informed and systemic plan of research priorities.

Real-World Evidence for COVID-19 Delta Variant's Effects on the Digestive System and Protection of Inactivated Vaccines from a Medical Center in Yangzhou, China: A Retrospective Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is rapidly disseminated worldwide, and it continues to threaten global public health. Recently, the Delta variant has emerged as the most dreaded variant worldwide. COVID-19 predominantly affects the respiratory tract, and studies have reported the transient effects of COVID-19 on digestive system function. However, the relationship between the severity of the Delta variant and digestive system function remains to be investigated. Additionally, data on the ability of the inactive Chinese vaccines (Sinovac or Sinopharm) to protect against the Delta variant or COVID-19-induced gastrointestinal symptoms in the real world are insufficient. Thus, the present retrospective observational study first attempted to use the total gastrointestinal symptom rating scale scores (GSRS) to quantify the possible changes in digestive system functions following the Delta variant infection in the early stage. In addition, the study discusses the potential of inactivated vaccines in preventing severe or critical symptoms or Delta variant-induced digestive system dysfunction. Methods: To evaluate the difference between mild illness group, moderate illness group, and severe or critical illness group, analysis of variance (ANOVA) was employed to compare the three groups' total gastrointestinal symptom rating scale scores (GSRS). A chi-squared test was used to compare the differences in the ratio of the abnormal biochemical measurements among the three groups first. Then, the percentage of the vaccinated population was compared among the three groups. Additionally, the ratio of the abnormal serum markers between the vaccinated and nonvaccinated cohorts was compared. A P value < 0.05 was considered statistically significant. Results: Significant differences were observed in the abnormal ratio of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), and Interleukin 6 (IL-6) ratio among the three groups (P < 0.05). Additionally, no significant difference was observed in the abnormal serum markers ratio between day 14 and day 21 after treatment (P > 0.05). A significant difference was observed in the total GSRS scores among the three groups and the ratio of the vaccinated population among the three groups (P < 0.05). A significant difference was observed in the ratio of the abnormal serum ALT and AST levels between the vaccinated and nonvaccinated cohorts (P < 0.05). Conclusions: In summary, serum AST, DBIL, LDH, and IL-6 levels are potential markers for distinguishing severe or critical patients in the early stage of the Delta variant infection. Additionally, changes in the levels of these serum makers are transient, and the levels can return to normal after treatment. Furthermore, severe gastrointestinal discomfort was significantly more prevalent in patients with severe or critical diseases and should thus be considered in patients diagnosed with Delta variant infection. Finally, inactivated vaccines may prevent severe or critical symptoms and Delta variant-induced liver dysfunction. Vaccination programs must be promoted to protect public health.

How scientific research reacts to international public health emergencies: a global analysis of response patterns.

As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.

How has academia responded to the urgent needs created by COVID-19? A multi-level global, regional and national analysis

In the context of the COVID-19 pandemic, gaining insights into how academia has responded to this urgent challenge is of great significance. This article presents academic response patterns at a global, regional and national level from an analysis of publication volume versus reported cases of COVID-19, scientific collaboration and research focus. We also compare academic activity associated with this newly emerging infection to that related to long-standing infections. Our results show that the research community has responded quickly to COVID-19. The highly developed countries, which have the highest number of confirmed cases, are also the major academic contributors. National-level analysis reveals diverse response patterns from different countries. Specifically, academic research in the United Kingdom remained at a relatively constant level throughout the whole year (2020), while the global share of China?s research output was prone to shift as its domestic pandemic status changed. Strong alliances have formed among countries with academic capabilities in response to the COVID-19 pandemic. The distribution of disciplines is relatively decentralised, indicating that a diverse and broad knowledge base contributes to the COVID-19 literature. Most of the analysed countries show dynamic patterns of research focus that vary over time as the pandemic evolves, except India. As one of the world?s biggest suppliers of vaccines, India makes consistent efforts on vaccine research, especially those related to pharmaceutical preparations. Our findings may serve as resources for fostering strategies to respond to future threats of pandemics.

Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19.

Background: The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19. Methods: We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels. Results: Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens. Conclusions: For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19.

SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including Gemella morbillorum, Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients, while Prevotella histicola, Streptococcus sanguinis, and Veillonella dispar were relatively increased. The abundance of G. haemolysans and L. hofstadii were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.

Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq.

B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11chigh CD95high) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.

Clinical features and risk factors for severe-critically ill COVID-19 adult patients in Jiangsu, China: A multiple-centered, retrospective study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) becomes a global pandemic in 2020. Early identification of severe ill patients is a top priority for clinicians. We aimed to describe clinical features and risk factors of severe-critically ill patients with COVID-19 in Jiangsu Province.This multi-centered retrospective study collected the information of 631 laboratory-confirmed COVID-19 patients hospitalized at 28 authorized hospitals in Jiangsu province from January 23, 2019 to March 13, 2020.A total of 583 adult patients with laboratory-confirmed COVID-19 were enrolled for final analysis, including 84 severe-critically ill patients and 499 mild-moderate patients. Median age of the severe-critically ill patients was 57.0 years old (interquartile range, 49.0-65.8), and 50 (59.5%) were males. Multisystemic laboratory abnormalities were observed on admission for severe-critically ill patients. These patients showed more noticeable radiologic abnormalities and more coexisting health issues as compared to the mild-moderate patients. Most of the severe-critically ill COVID-19 patients became deteriorated in 2 weeks after diagnosis. Age, D-dimer, and lymphocytes were independently associated with the progression of severe-critically illness.Older age, higher D-dimer levels and less lymphocyte counts on admission are potential risk factors for COVID-19 patients to develop into severe and critically illness.

Clinical characteristics of asymptomatic carriers of novel coronavirus disease 2019: A multi-center study in Jiangsu Province.

Asymptomatic SARS-CoV-2-infected individuals are thought to play major roles in virus transmission. This study aimed to analyze the characteristics of asymptomatic carriers with COVID-19 to control the spread of the virus. We retrospectively investigated the clinical characteristics of 648 consecutive subjects who were enrolled in the study and were divided into asymptomatic carriers, mild cases, ordinary cases, severe or critical cases, and evaluated their impact on disease severity by means of Spearman correlation and multiple regression analyses. Receiver operating characteristic curve analysis was conducted to determine the optimum cutoff levels of laboratory findings for diagnostic predictors of asymptomatic carriers of COVID-19. In our study, a total of 648 subjects on admission with a mean age of 45.61 y including 345 males and 303 females were enrolled in our study. The leukocyte, lymphocyte, eosinophil, platelet, C-reactive protein, interleukin-6, CD3+, CD4+, and CD8 + T lymphocyte levels, and the erythrocyte sedimentation rate differed significantly among the groups (all p ≤ 0.05). Disease severity was negatively associated with the CD3+ (r = -0.340; p < 0.001), CD4+ (r = -0.290; p = 0.001) and CD8+ (r = -0.322; p < 0.001) T lymphocyte levels. The significant diagnostic predictors of asymptomatic carriers of COVID-19 included the blood cell, cytokine, and T lymphocyte subset levels. Inflammation and immune response may play important roles in disease progression. Hence, the laboratory parameters identified should be considered in clinical practice, which provide new insights into the identification of asymptomatic individuals and the prevention of virus transmission.

Clinical Characteristics and Predictors of Disease Progression in Severe Patients with COVID-19 Infection in Jiangsu Province, China: A Descriptive Study.

BACKGROUND: We studied patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2, a virus that originated in Wuhan, China, and is spreading over the country including Jiangsu Province. We studied the clinical characteristics and therapies of severe cases in Jiangsu Province. METHODS: A multicenter retrospective cohort study was conducted to analyze clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection in Jiangsu Province between January 24, 2020 and April 20, 2020. The improvement and deterioration subgroups were compared to identify predictors of disease progression. RESULTS: A total of 653 infected cases with COVID-19 were reported in Jiangsu Province, of which 60 severe cases were included in this study. Up until April 20, 2020, the mortality of severe patients was 0%. The median age was 57 years. The average body mass index of these patients was 25 kg/m². White blood cell counts decreased in 45.0% of patients, lymphopenia in 63.3%, thrombocytopenia in 13.3% and procalcitonin levels in 88.3% of the patients were less than 0.5 ng/mL. There were no statistically significant differences in immunoglobulin therapy and GCs therapy between the improvement and deterioration subgroups. Logistic regression analysis identified higher levels of troponin T (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.00-1.08; P = 0.04), antiviral therapy with aerosol inhalation of interferon (OR: 6.33; 95% CI: 1.18-33.98; P = 0.03), and the application of non-invasive mechanical ventilation (OR: 1.99; 95%CI: 1.17-3.41; P = 0.01) as predictors of disease progression, whereas higher lymphocyte count (OR: 0.11; 95% CI: 0.02-0.57; P = 0.01) and early prone ventilation were associated with improvement (OR: 0.11; 95% CI: 0.01-0.98; P = 0.04). CONCLUSIONS: COVID-19 infection had a low mortality rate in Jiangsu Province, China. The higher levels of troponin T and lower lymphocyte count were predictors of disease progression. Early prone ventilation may be an effective treatment for severe cases.