The assembled and annotated genome of the masked palm civet (Paguma larvata).

BACKGROUND: The masked palm civet (Paguma larvata) acts as an intermediate host of severe acute respiratory syndrome coronavirus (SARS-CoV), which caused SARS, and transfered this virus from bats to humans. Additionally, P. larvata has the potential to carry a variety of zoonotic viruses that may threaten human health. However, genome resources for P. larvata have not been reported to date. FINDINGS: A chromosome-level genome assembly of P. larvata was generated using PacBio sequencing, Illumina sequencing, and Hi-C technology. The genome assembly was 2.44 Gb in size, of which 95.32% could be grouped into 22 pseudochromosomes, with contig N50 and scaffold N50 values of 12.97 Mb and 111.81 Mb, respectively. A total of 21,582 protein-coding genes were predicted, and 95.20% of the predicted genes were functionally annotated. Phylogenetic analysis of 19 animal species confirmed the close genetic relationship between P. larvata and species belonging to the Felidae family. Gene family clustering revealed 119 unique, 243 significantly expanded, and 58 significantly contracted genes in the P. larvata genome. We identified 971 positively selected genes in P. larvata, and one known human viral receptor gene PDGFRA is positively selected in P. larvata, which is required for human cytomegalovirus infection. CONCLUSIONS: This high-quality genome assembly provides a valuable genomic resource for exploring virus-host interactions. It will also provide a reliable reference for studying the genetic bases of the morphologic characteristics, adaptive evolution, and evolutionary history of this species.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Effects of SARS-CoV-2 Infection During Late Pregnancy on Early Childhood Development: A Prospective Cohort Study.

Background: There is little direct or indirect evidence of the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on early childhood development. Methods: We conducted a prospective, observational cohort study in China from May 1 to October 31, 2020, that enrolled 135 mother-infant dyads: 57 dyads in the infection cohort and 78 in the non-infection cohort. Among all infants, 14.0% were preterm birth in the infection cohort and 6.4% in the non-infection cohort. Participants were followed by telephone interviews to collect demographic characteristics, medical records of coronavirus disease 2019, breastfeeding data, and early childhood development was assessed by the Age and Stage Questionnaire (ASQ-3) and Age and Stage Questionnaire Social-Emotional (ASQ:SE-2) Chinese versions at 3 months after childbirth. We used multivariable Poisson regression models to estimate the relative risk (RR) of SARS-CoV-2 infection. Multivariable linear regression models and a mediation model were used to test the direct and indirect associations between SARS-CoV-2 infection and the ASQ-3 score. This study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (No. IRB00006761-M2020127). Results: In the infection cohort, 13.6% of the children showed social-emotional developmental delay, and 13.5% showed overall developmental delay. The corresponding rates in the non-infection cohort were 23.4 and 8.1%. Compared with the non-infection cohort, SARS-CoV-2 infection during pregnancy did not increase the risk of social-emotional (RR = 0.87, 95% CI: 0.51-1.49) or overall (RR = 1.02, 95% CI: 0.60-1.73) developmental delay. The mediation model showed that SARS-CoV-2 infection indirectly affected the ASQ-3 score by increasing the length of mother-infant separation. Conclusions: SARS-CoV-2 during late pregnancy did not increase the risk of developmental delay of the offspring 3 months after delivery. However, SARS-CoV-2 may have indirect effects on early childhood development by increasing mother-infant separation.

Efficacy and safety of antiviral therapy in critically ill patients with mechanical ventilation: a meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVES: Viral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation. METHODS: Data sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis. RESULTS: Nine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79-1.11, I2 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14-0.37, I2 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73-1.05, I2 0%). CONCLUSIONS: No association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

Questionnaire Survey on the Current Situation and Experience in Prevention and Control Measures at Urology Clinics During the COVID-19 Epidemic in China.

COVID-19, the coronavirus disease 2019; SARS-CoV-2, the coronavirus 2; ACE2, angiotensin converting enzyme 2; S protein, spiked glycoprotein; TMPRSS2, transmembrane serine protease 2; WHO, World Health Organization. Purpose: Although the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has been viably controlled in China, a new normal in healthcare strategies has become standard in China and worldwide. We conducted a questionnaire study to disseminate the experience from China in terms of urology outpatient prevention and control measures under standardized prevention policies against COVID-19. Participants and Methods: From May 3, 2020 to June 25, 2020, we conducted an anonymous cross-sectional questionnaire study, focused on the status of and experiences with outpatient urology prevention and control measures during the COVID-19 pandemic. The targeted respondents were urologists in mainland China, covering all levels of hospitals and clinics. Results: A total of 216 (97%) valid responses were collected. We found that 183 (85%) respondents were from outside of Hubei province in China. One-hundred-and-fifty-eight (73%) respondents believed that SARS-CoV-2 could be detected in urine, and that protection against urine exposure was needed. Over 80% of respondents recommended WeChat application or similar online video meetings for virtual outpatient consultations. The suggested flowcharts and recommendations to prevent new cases were easy to understand and approved by most physicians, which could provide reference for outpatient prevention and control. We still need to make adequate preparations under the new normal of the COVID-19 Epidemic, especially for those suspected of being infected. Conclusions: Although the scientific validation of the questionnaire is limited, it provides a first snapshot of the experiences relating to the prevention and control measures in urology clinics in China, and can inform future policies in this field.

Malignancy is a risk factor for higher COVID-19 severity:A meta-analysis.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has been an almost global pandemic with significant public health impacts. The increasing prevalence of malignancy has become a leading cause of human mortality. However, conflicting findings have been published on the association between malignancy and COVID-19 severity. This study aims to assess the pooled proportion of malignancy amongst 2019-nCov patients and to investigate the association between malignancy and COVID-19 severity. METHODS: Correlative studies were identi?ed by systematically searching electronic databases (PubMed, Web of Sciences and Embase) up to September 2, 2020. All data analyses were carried out using Stata 15.0. RESULTS: Twenty-nine studies consisting of 9475 confirmed COVID-19 patients (median age 54.4 years [IQR 49-62], 54.0% men) were included. The overall proportion of malignancy was 2.5% (95% CI 1.6%-3.4%). The proportion of malignancy was higher in patients with severe/critical 2019-nCoV than those in non-severe/non-critical group (3.9% [95% CI 2.0-6.3] vs 1.4% [95% CI 0.8-2.2]). Furthermore, pre-existing malignancy was associated with more than twofold higher risk of severe/critical patients with COVID-19 (OR 2.25, 95% CI 1.65-3.06 I2 = 0.0%). CONCLUSION: Malignancy was associated with up to 2.3-fold higher risk of severe/critical COVID-19 and may serve as a clinical predictor for adverse outcomes.

A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19.

BACKGROUND: The incidence of venous thromboembolic events (VTE) in patients with COVID-19 is generally high but varies markedly. However, the relationship between anticoagulation and mortality in patients with COVID-19 is still unclear. METHODS: We performed a systematic review and meta-analysis to determine the incidence of VTE and evaluate the role of anticoagulation in patients with COVID-19. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: After a database search, 25 observational studies (20 on VTE incidence and 5 on the relationship between anticoagulation and mortality) were included. The pooled incidence rates of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in hospitalised COVID-19 patients were 21% (95% CI 15-27%), 15% (95% CI 10-20%), and 27% (95% CI 19-36%), respectively. A meta-analysis of five studies found that anticoagulation was not associated with an increased risk of mortality in hospitalised COVID-19 patients (RR = 0.86, 95% CI, 0.69-1.09, P = 0.218; I2 = 47.4%). CONCLUSIONS: In conclusion, the incidence of VTE among hospitalised COVID-19 patients was high. Clinical trials are urgently needed to evaluate the roles of prophylactic and therapeutic anticoagulation in COVID-19.

Impact of Covid-19 in pregnancy on mother's psychological status and infant's neurobehavioral development: a longitudinal cohort study in China.

BACKGROUND: Evidence concerning the long-term impact of Covid-19 in pregnancy on mother's psychological disorder and infant's developmental delay is unknown. METHODS: This study is a longitudinal single-arm cohort study conducted in China between May 1 and July 31, 2020. Seventy-two pregnant patients with Covid-19 participated in follow-up surveys until 3 months after giving birth (57 cases) or having abortion (15 cases). We collected data from medical records regarding Covid-19, delivery or abortion, testing results of maternal and neonatal specimens, and questionnaires of quarantine, mother-baby separation, feeding, and measuring of mothers' mental disorders and infants' neurobehavioral disorders. RESULTS: All cases infected in the first trimester and 1/3 of cases infected in the second trimester had an abortion to terminate the pregnancy. 22.2% of pregnant patients were suffering from post-traumatic stress disorder or depression at 3 months after delivery or induced abortion. Among 57 live births, only one neonate was positive of nucleic acid testing for throat swab, but negative in repeated tests subsequently. The median duration of mother-baby separation was 35 days (interquartile range 16 to 52 days). After the termination of maternal quarantine, 49.1% of mothers chose to prolong the mother-baby separation (median 8 days; IQR 5 to 23 days). The breastfeeding rate was 8.8% at 1 week after birth, 19.3% at the age of 1 month, and 36.8% at the age of 3 months, respectively. The proportion of "monitoring" and "risk" in the social-emotional developmental domain at the age of 3 months was 22.7% and 63.6%, respectively. After the adjustment of preterm, neonatal sex, admitted to NICU, and the mother's Covid-19 condition, the negative associations were significantly identified (p < 0.05) between mother-baby separation days and three developmental domains: communication, gross motor, and personal-social. CONCLUSIONS: There is no definite evidence on vertical transmission of SARS-CoV-2. In addition to control infection risk, researchers and healthcare providers should pay more attention to maternal mental health and infant's feeding, closeness with parents, and early development.

Dynamic changes of liver function parameters in patients with coronavirus disease 2019: A multicenter, retrospective study (preprint)

Background: Liver injuries in patients with coronavirus disease 2019 (COVID-19) have been reported, however, the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is obscure.  Methods: In this multicenter, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various timepoints referred to SARS-CoV-2 shedding, and 3 to 7 days before first detection of viral shedding was regarded as reference baseline.Results: Totally, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) cases had self-medications history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal rates of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL), respectively. ALT and AST abnormal rates and levels did not show any significantly dynamic change during the full period of viral shedding (all P > 0.05). GGT abnormal rate (P = 0.008) and level (P = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneously significant increases of ALP abnormal rates and levels were observed. TBIL abnormal rates and levels significantly increased on day 1 and 5 of viral shedding (all P < 0.05). Albumin abnormal decrease rates increased and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all P < 0.05). Thirteen (18.6%) patients had chronic liver diseases, two of them died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver diseases during SARS-CoV-2 shedding.Conclusions: The SARS-CoV-2 does not directly lead to elevations of ALT and AST, but may result in elevations of GGT and TBIL, the albumin decreased extraordinarily even SARS-CoV-2 shedding discontinued.

Pregnancy with COVID-19: Management considerations for care of severe and critically ill cases.

Pregnant women are a potentially highly vulnerable population due to anatomical, physiological, and immunological changes under the COVID-19 pandemic. Issues related to pregnancy with COVID-19 attracted widespread attention from researchers. A large number of articles were published aiming to elaborate clinical characteristics and outcomes of pregnant women infected with COVID-19, in order to provide evidence for management. The existing data suggest that the overall prognosis of pregnancy with COVID-19 is promising when compared with that of other previous coronaviruses. There is still maternal morbidity and mortality related to COVID-19 reported. However, the optimal management of severe and critically ill cases of COVID-19-infected pregnancy is poorly clarified. The possibility of postpartum exacerbation in pregnancy with COVID-19 is also worthy of attention for obstetricians. This review makes further elaboration of the above issues.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.

ß-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.

Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single-centre, observational cohort study.

BACKGROUND: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia. METHODS: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed. RESULTS: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7-99.4]; P<0.01). CONCLUSIONS: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients.