ABSTRACT
Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks. We have screened a library of microbial metabolites to discover new SARS-CoV-2 inhibitors. To facilitate this screening effort, we generated a recombinant SARS-CoV-2 Delta variant carrying the nano luciferase as a reporter for measuring viral infection. Six compounds were found to inhibit SARS-CoV-2 at the half maximal inhibitory concentration (IC50) below 1 mM, including the anthracycline drug aclarubicin that markedly reduced viral RNA-dependent RNA polymerase (RdRp)-mediated gene expression, whereas other anthracyclines inhibited SARS-CoV-2 by activating the expression of interferon and antiviral genes. As the most commonly prescribed anti-cancer drugs, anthracyclines hold the promise of becoming new SARS-CoV-2 inhibitors.
Subject(s)
COVID-19 , Virus DiseasesABSTRACT
Objective: To assess the risk of public health emergencies, both the indigenous ones and the imported ones, which might occur in the mainland of China in October 2022.
ABSTRACT
Background The lifestyles of children and adolescents have changed extensively during the COVID-19 pandemic due to school suspension and social distancing measures, which can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic. Method As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. We investigated the pandemic's effects on sleep parameters using multivariate regression, adjusting for age, sex, household income, seasonality and presence of mental disorders, and the moderators and mediators of the effects. Findings Between 1 September 2019 and 2 June 2021, 791 primary and 442 secondary school students were recruited and analysed. Assessment during COVID predicted a longer sleep latency in both groups on school days (95% CI= 1.0-5.2 minutes, adjusted p-value= 0.010; and 95% CI= 3.9-13.0 minutes, adjusted p-value= 0.004, respectively) and non-school days (95% CI= 1.7-7.2 minutes, adjusted p-value= 0.005; 95% CI= 3.4-13.7 minutes, adjusted p-value= 0.014, respectively). Low household income was a moderator for later bedtime (adjusted p-value= 0.032) and later sleep onset (adjusted p-value= 0.043) during non-school days among secondary school students. Sex and digital leisure time were respectively not a moderator and mediator of the pandemic's effect on sleep parameters. Interpretation Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and effects of anti-epidemic measures on the health gaps of the youth should be considered. Funding Government of the Hong Kong Special Administrative Region, Food and Health Bureau, Health and Medical Research Fund (Ref. No.: MHS-P1(Part 1)-CUHK).
Subject(s)
COVID-19 , Mental DisordersABSTRACT
Background Dietary culture affects people's cognition and attitudes toward nutrition, and it even dictates people's dietary behavior. This study aimed to assess the dietary-culture-related KAP of Chinese netizens during the corona virus disease 2019(COVID-19) pandemic.Methods A cross-sectional survey was conducted using an online KAP questionnaire in China. Volunteers were recruited at Southwest Medical University and were first trained to unify standards of distributing questionnaires. Participants were recruited by convenient- and snowball-sampling methods. Multiple regression analysis was used to analyze the influential factors.Results After 50 days of investigation, 3514 participants (40.6% men) were valid. The mean score of netizens’ nutrition knowledge was 3.9 ± 2.2 and the mean awareness rate was 31.7%. Women participants in the age group of 30–39 with higher education level had higher nutrition knowledge qualification rate. During the COVID-19 pandemic, the positive rate of attitude toward dietary-culture-related nutrition was 93.7%, and women netizens who had higher level of education and immigrated from other places had better attitudes. Moreover, the positive rate of dietary habits was 90.7%, and older women netizens had better dietary behavior.Conclusions Netizens’ knowledge of nutrition was poor, but their dietary habits and attitudes toward dietary-culture-related nutrition were generally positive, which was also a great progress for Chinese people.
Subject(s)
COVID-19ABSTRACT
No specific effective therapeutic drugs have been identified for COVID-19. Critically ill COVID-19 36 patients in the ICU experience high mortality. This project aims to study the effects of traditional 37 Chinese medicine (TCM) treatment on deadly outcomes caused by COVID-19. A total of 123 critically 38 ill COVID-19 patients who received close monitoring at the ICU of Vulcan Hill Hospital between 39 ICU patients received supportive management. Eighty-one patients were given additional TCM 41 treatment. Clinical characteristics during the treatment period (up to 39 days) and the clinical outcome 42 of each patient were closely monitored and analysed. We observed that patients treated with TCM had 43 lower mortality than the non-TCM treatment group (16 of 81 vs. 31 of 42; 0.3 person/month vs. 2.9 44 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with 45 improved survival [multivariate HR, 0.13; 95% confidence interval (CI), 0.06–0.24; P < 0.001]. 46 Furthermore, we found that TCM treatment could partially improve the inflammation status by 47 reducing the levels of proinflammatory cytokines and recovering multiple organic functions. TCM 48 treatment may decrease inflammation status by reducing the level of proinflammatory cytokines and 49 allowing the recovery of multiple organic functions, which could improve the survival rate of critically 50 ill COVID-19 patients.
Subject(s)
COVID-19ABSTRACT
The novel coronavirus 2019 (COVID-19) rapidly spreading around the world and turns into a pandemic situation, consequently, detecting the coronavirus (COVID-19) affected patients are now the most critical task for medical specialists. The deficiency of medical testing kits leading to huge complexity in detecting COVID-19 patients worldwide, resulting in the number of infected cases is expanding. Therefore, a significant study is necessary about detecting COVID-19 patients using an automated diagnosis method, which hinders the spreading of coronavirus. In this paper, the study suggests a Deep Convolutional Neural Network-based multi-classification framework (COVMCNet) using eight different pre-trained architectures such as VGG16, VGG19, ResNet50V2, DenseNet201, InceptionV3, MobileNet, InceptionResNetV2, Xception which are trained and tested on the X-ray images of COVID-19, Normal, Viral Pneumonia, and Bacterial Pneumonia. The results from 4-class (Normal vs. COVID-19 vs. Viral Pneumonia vs. Bacterial Pneumonia) demonstrated that the pre-trained model DenseNet201 provides the highest classification performance (accuracy: 92.54%, precision: 93.05%, recall: 92.81%, F1-score: 92.83%, specificity: 97.47%). Notably, the DenseNet201 (4-class classification) pre-trained model in the proposed COV-MCNet framework showed higher accuracy compared to the rest seven models. Important to mention that the proposed COV-MCNet model showed comparatively higher classification accuracy based on the small number of pre-processed datasets that specifies the designed system can produce superior results when more data become available. The proposed multi-classification network (COV-MCNet) significantly speeds up the existing radiology based method which will be helpful for the medical community and clinical specialists to early diagnosis the COVID-19 cases during this pandemic.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.
Subject(s)
COVID-19ABSTRACT
Background: COVID-19 has become a global pandemic. Studies about SARS-CoV-2 co-infection with influenza A virus (IAV) in the influenza season will contribute to the antiviral interventions of co-infected patients.Methods: A cohort of 145 COVID-19 patients in Wuhan union hospital were reviewed and we found 2 patients were co-infected with both SARS-CoV-2 and IAV. Then we searched from PubMed, Web of Science and CNKI with combinations of the following key words: “COVID-19, SARS-COV-2, influenza A and co-infection” from January 1 up to May 1, and 6 studies were included in this descriptive analysis. Results: Of the 13 co-infected patients, 2 were from Wuhan union hospital, another 11 were collected from the reports published on PubMed, Web of Science and CNKI. Of the 13 patients, the median age was 50 years (IQR, 40.5-67.5). Among the 13 patients, 7 (53.8%) were severe types. The most common symptoms among the 13 patients were cough (100%), fever (92.3%) and dyspnea (76.9%). 8 patients had lymphocytopenia on admission and all the 13 patients had abnormal radiological changes. The median time from symptom onset to hospital admission was 4.5 days (IQR, 2.75-5.5), and the median time of hospital stay was 17 days (IQR,15-20). Conclusion: Patients with both SARS-COV-2 and IAV infection showed similar changes in symptoms and radiological images with patients infected with SARS-COV-2 only. SARS-COV-2 co-infection with IAV can lead to more severe clinical condition but had similar hospital stay compared with patients infected with SARS-COV-2 only in the fast review.
Subject(s)
Coinfection , Dyspnea , Fever , Cough , COVID-19 , LymphopeniaABSTRACT
Since SARS-CoV-2 infection was first identified in December 2019, it spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes, including spermatogonia, Leydig and Sertoli cells. However, there is no clinical evidence about whether SARS-CoV-2 infection can affect male gonadal function so far. In this study, we compared the sex-related hormones between 81 reproductive-aged men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that serum luteinizing hormone (LH) was significantly increased, but the ratio of testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in males with COVID-19. Besides, multivariable regression analysis indicated that c-reactive protein (CRP) level was significantly associated with serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones, alerting more attention to gonadal function evaluation among patients recovered from SARS-CoV-2 infection, especially the reproductive-aged men.
Subject(s)
COVID-19ABSTRACT
BackgroundIn December 2019, a cluster of cases of acute respiratory illness, novel coronavirus-infected pneumonia, occurred in Wuhan, Hubei Province, China. Health care workers exposure to a high density of patients are at extremely high risk of becoming infected at the early outbreak of this disease for not realizing the fact of human-to-human transmission among close contacts at that time. The false-negative nasopharyngeal swabs of SARS-CoV-2 caused the delayed diagnosis of COVID-19. The nosocomial transmission of SARS-CoV-2 in negative nasopharyngeal swabs cases were not reported previously. We wish to alert the potential transmission risk in COVID-19 patients with negative swab tests to the clinicians and stress the role of serological detection of anti-SARS-CoV-2.MethodsThis study evaluated a total of 6 cases and four of them were health care providers who worked in the same ward. All epidemiological and clinical information was collected. Respiratory samples of the patients were tested for influenza A, influenza B and respiratory syncytial virus (RSV) RNA The reverse-transcription–polymerase chain reaction (RT-PCR) assay of SARS-CoV-2 RNA was conducted and serological detection of anti-SARS-CoV-2-IgG/IgM is performed by chemiluminescence immunoassay kit.ResultsWe reported two related clusters of COVID-19 cases. The first cluster is a nosocomial infection of four health care providers at early January in one ward of university hospital. One of them made sequential familial cluster of infection. For total six cases, four of them (66.7%) showed negative RNA of SARS-CoV-2 by nasopharyngeal swabs. All patients received either self-quarantined at home or were admitted to hospital for isolated treatment. All recovered and had anti-SARS-CoV-2 IgG and/or IgM positive (100%) for serological detection of SARS-CoV-2 at recovery stage.ConclusionsOur study provides a cautionary warning that negative results of nasopharyngeal swabs of suspected SARS-CoV-2 infection can increase the risk of nosocomial infection among health care providers. Serologic detection for anti-SARS-CoV-2 IgG and/or IgM is an important test in the assistant diagnosis of COVID-19.