Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai.

Objective: To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods: A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result: Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8-15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8-15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50-64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions: Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai

Objective To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8–15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8–15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50–64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Decreased Hospital-Acquired Respiratory Infections among elder Inpatients in General Hospital during the COVID-19 Pandemic (preprint)

Background In order to avoid nosocomial transmission of COVID-19, various prevention and control measures have been strictly implemented in medical institutions. These strict measures can probably reduce the incidence of hospital acquired respiratory infections. We conducted this study to assess changes in the prevalence of hospital acquired respiratory infections during a period of national attention to the prevention the COVID-19 pandemic.Methods We retrospectively analyzed the clinical data of patients from October to December 2019 and from October to December 2020. The diagnostic of hospital acquired respiratory infections was based on CDC/NHSN criteria. We compared the incidence and mortality rate of hospital acquired respiratory infections between these 2 periods. We also used multivariate logistics regression analysis for risk factors associated with mortality.Results In 2020, a total of 2921 patients’ data were surveyed, as compared with 2211 patients in 2019. Incidence of hospital acquired respiratory infections was lower in 2020 (2.9% vs. 4.7%, P = 0.001). In hospital mortality of patients with hospital acquired respiratory infections had no significant difference (38.4% vs. 30.5%, p = 0.252). Multivariate logistics regression analysis showed that severe pneumonia (RR = 28.235, 95%CI: 10.122, 78.759, p = 0.000), previous malignant tumor (RR = 4.599, 95%CI: 1.768, 11.963, p = 0.002) and cardiac injury (RR = 2.264, 95%CI: 0.935, 5.485, p = 0.07) were associated with an increased risk of mortality.Conclusions The incidence of hospital acquired respiratory tract infections was significantly decreased during COVID-19 period as a result of the adoption of infection prevention and control measures in medical institutions. Elder patients with severe pneumonia and previous malignant tumor were at high risk for death in hospital.

Conserved longitudinal alterations of anti-S-protein IgG subclasses in disease progression in initial ancestral Wuhan and vaccine breakthrough Delta infections

Introduction COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

How Do Nature-Based Activities Benefit Essential Workers during the COVID-19 Pandemic? The Mediating Effect of Nature Connectedness.

Although many studies have suggested that nature-based activities have a healing effect on human beings, there is little research on the underlying mechanism. This study investigated the role of nature connectedness in the relationship between the perception of nature and individuals' physical and psychological health. We recruited essential workers who participated in disease prevention and control during the COVID-19 pandemic and their family members as the subjects for this study. The stress levels experienced by this group made them an ideal sample. The results of a survey-based study showed that nature-based activities had a positive effect on alleviating state anxiety levels. The results also showed that nature-based activities affected perceived restoration via the feeling of nature connectedness. This study examined the healing effect of nature-based activities that stimulate the five senses and nature connectedness and explored the potential of nature-based treatments for people experiencing high levels of stress.

Realized higher-order moments spillovers between commodity and stock markets: Evidence from China

Using 5-min data of Chinese stock market index and eight Chinese commodity futures (soybean, wheat, corn, gold, silver, copper and aluminum, crude oil) from March 26, 2018 to October 22, 2020, we analyze the dynamic spillover connectedness of returns and realized moments, including realized volatility, realized skewness, and realized kurtosis, during various shock periods via a time-varying parameter vector autoregression (TVP-VAR) connectedness approach. The results show that spillover effects between stock and commodity markets intensify during shock periods such as ‘Trade disputes between China and the United States’ and ‘COVID-19’. Volatility spillovers are relatively stronger;however, higher-order moment spillovers contain additional information of stock-commodity spillovers that cannot be observed from volatility spillovers. Shocks from the silver market influence all three realized moments of the entire financial markets. Soybean, corn, aluminum, and oil markets are easily affected by other markets. The contribution of wheat to the system of spillovers between stock and commodity markets is only observed at higher-order moments. Further analyses involving OLS and quantile regressions show that total spillovers are generally affected by the US stock market and economic uncertainties as well as the COVID epidemic. We construct daily realized volatility, skewness, and kurtosis using 5-min data of eight Chinese commodity futures and the Chinese stock market index from March 26, 2018 to October 22, 2020, then analyse the dynamic spillovers of realized moments among these markets. The results show that the spillover effects between commodity and stock markets intensify during shock periods such as ‘trade disputes between China and the United States’ and ‘COVID-19’. Volatility spillovers are relatively stronger than spillovers in skewness or spillovers in kurtosis;however, spillovers in higher-order moments seem to contain additional information. Shocks from the silver market influence realized moments of other markets. Soybean, corn, aluminium, and oil markets are affected by other markets. The contribution of wheat as a net transmitter to the system of spillovers between stock and commodity markets is only observed at higher-order realized moments. The results from OLS and quantile regressions show that the total spillovers are generally affected by the US stock market, economic uncertainties, and the COVID-19 outbreak.

Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study.

Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide association study (GWAS) of 78,592 European-ancestry participants identified single nucleotidepolymorphisms (SNPs) that can be utilized to genetically predict LTL. Summary-level data for COVID-19 outcomes were analyzed from the COVID-19 Host Genetics Initiative. A two-sample bidirectional Mendelian randomization (MR) study was designed to evaluate these causal relationships. Using an inverse-weighted MR analysis and population-based controls, genetically predicted LTL did not reveal any significant association with COVID-19 susceptibility (odds ratio (OR): 0.94; 95% CI: 0.85-1.04; p = 0.202) or severity (OR: 0.85; 95% CI: 0.70-1.03; p = 0.099). Similar results were found for five other definitions of cases/controls and/or COVID-19 outcomes. Six additional MR methods and sensitivity analyses were conducted after removing variants with potential horizontal pleiotropy and including variants at a liberal significance level, which produced similar results. Using SNPs identified for the prediction of LTL from another GWAS study, we found a non-significant association for COVID-19 susceptibility or severity with narrower CIs toward the null hypothesis. No proof of genetically predicted COVID-19 phenotypes remained causally associated with genetically predicted LTL, and the null association was consistent with a lack of significant genetic correlation. Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity.

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Changes in Notifiable Infectious Diseases in China During the COVID-19 Pandemic: A National Surveillance Study (preprint)

Background: Nationwide nonpharmaceutical interventions (NPI) were used to combat the novel coronavirus disease (COVID-19) during 2020 in the mainland of China. These NPIs have proven effective on mitigating the spread of COVID-19, but their broad impact on other diseases remains under-investigated. In this study, we aim to assess whether such broad impact exists on notifiable diseases in China.Methods: Weekly incidence and mortality data for 31 major notifiable infectious diseases at the province level were extracted from the China Information System for Disease Control and Prevention from 2014 to 2020. We assessed the impact of NPIs by contrasting the incidences of each infectious disease in predefined COVID-19 phases during 2020 to the average incidences in the corresponding time intervals during 2014-2019.Findings: We observed decreased incidences of most diseases during the phases after the lockdown of Wuhan. In general, respiratory diseases and gastrointestinal or enteroviral diseases were more affected than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Seasonal flu and rubella were the most sensitive to the NPIs, with reductions of 67-99% in incidence rates throughout the NPI-implemented phases in China (Jan 27-Dec 31, 2020). Among gastrointestinal or enteroviral diseases, the hand, foot and mouth disease (HFMD) was subject to the largest declines during Jan 27-Aug 31, 2020, with >90% reduction in incidence rate. Phases with more stringent NPIs were associated with more reductions. Non-respiratory diseases, particularly HFMD, gonorrhea and brucellosis, rebounded towards the end of the year as the NPIs were relaxed.Interpretation: NPIs are broadly effective in containing infectious diseases. Less disruptive NPIs such as wearing face masks are still effective in mitigating respiratory diseases but are not adequate for containing non-respiratory diseases.Funding Statement: This work was supported by grants from the National Natural Science Funds [91846302, 81825019], the China Mega-Project on Infectious Disease Prevention [2018ZX10713001, 2018ZX10713002, 2018ZX10201001 and 2017ZX10103004], and the US National Institutes of Health [R56 AI148284].Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: Missing.

Multifaceted Functions of CH25H and 25HC to Modulate the Lipid Metabolism, Immune Responses, and Broadly Antiviral Activities

With the frequent outbreaks of emerging infectious diseases in recent years, an effective broad-spectrum antiviral drug is becoming an urgent need for global public health. Cholesterol-25-hydroxylase (CH25H) and its enzymatic products 25-hydroxycholesterol (25HC), a well-known oxysterol that regulates lipid metabolism, have been reported to play multiple functions in modulating cholesterol homeostasis, inflammation, and immune responses. CH25H and 25HC were recently identified as exerting broadly antiviral activities, including upon a variety of highly pathogenic viruses such as human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah virus (NiV), Rift Valley fever virus (RVFV), and Zika virus (ZIKV). The underlying mechanisms for its antiviral activities are being extensively investigated but have not yet been fully clarified. In this study, we summarized the current findings on how CH25H and 25HC play multiple roles to modulate cholesterol metabolism, inflammation, immunity, and antiviral infections. Overall, 25HC should be further studied as a potential therapeutic agent to control emerging infectious diseases in the future.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis (preprint)

Background：In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. Objectives: We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. Methods: In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed.Results: On admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-Dimer levels were higher in COVID-19 patients (P<0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R=0.426, P<0.05), and after treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy.Conclusions: Elevated baseline D-dimer levels are associated with inflammation in COVID-19 patients, and the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.