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1.
Nat Commun ; 12(1): 7083, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1555251

ABSTRACT

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

2.
Preprint in English | Other preprints | ID: ppcovidwho-295327

ABSTRACT

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1,067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.

3.
Front Immunol ; 12: 715023, 2021.
Article in English | MEDLINE | ID: covidwho-1477819

ABSTRACT

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/mortality , Mycoses/epidemiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/mortality , Bronchoalveolar Lavage Fluid/microbiology , CD4 Lymphocyte Count , Female , Humans , Leukocytes, Mononuclear/immunology , Liver/injuries , Liver/virology , Lymphopenia/immunology , Male , Middle Aged , Mycoses/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , T-Lymphocytes/immunology
4.
Integr Med Res ; 10: 100798, 2021.
Article in English | MEDLINE | ID: covidwho-1472010

ABSTRACT

Background: We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. Methods: The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. Results: The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. Conclusion: We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.

5.
Curr Top Med Chem ; 2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1463385

ABSTRACT

As a traditional Chinese medicine, Shuang-Huang-Lian (SHL) has been widely used for treating infectious diseases of the respiratory tract such as encephalitis, pneumonia and asthma. During the past few decades, considerable research has focused on the pharmacological action, pharmacokinetic interaction with antibiotics and clinical applications of SHL. A huge and more recent body of pharmacokinetic study supports the combination of SHL and antibiotics has different effects such as antagonism and synergism. SHL has been one of the best-selling traditional Chinese medicine (TCM) products. However, there is no system review of SHL preparations, ranging from protection against respiratory tract infections to interaction with antibiotics. Since their important significance in clinical therapy, the pharmacodynamic, pharmacokinetic, and interactions with antibiotics of SHL were reviewed and discussed. In addition, this review attempts to explore the possible potential mechanism of SHL preparations in prevention and treatment of COVID-19. We are concerned about what is known of the effects of SHL against virus, bacterium, and its interactions with antibiotics, providing a new strategy for expanding the clinical research and medication of SHL preparations.

6.
iScience ; 24(10): 103186, 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1446742

ABSTRACT

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

9.
Cell Discov ; 7(1): 76, 2021 Aug 31.
Article in English | MEDLINE | ID: covidwho-1380898

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38-0.63 for T allele; P = 1.38 × 10-8; and index rs10831496: OR = 1.66; 95% CI, 1.38-1.98 for A allele; P = 4.04 × 10-8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

10.
Medicine (Baltimore) ; 100(33): e26760, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1367077

ABSTRACT

ABSTRACT: The present study reported early clinical outcomes and perioperative precautions for medical staffs during joint arthroplasty procedures in SARS-CoV-2-infected patients.The medical records of 8 patients with SARS-CoV-2 infection who underwent joint arthroplasty from January 19 to September 24, 2020 were retrospectively reviewed and analyzed. Perioperative precautions and follow-up (time length varies from 6 month to 13 months, 11 months in average) for SARS-CoV-2 infection of medical staffs were reported.All patients recovered well from both the primary disease and SARS-CoV-2 infection. Significant improved Visual analogue scale was observed with no major complications or recurrence of the COVID-19 at discharge. There was no evidence indicating SARS-CoV-2 infection in any health providers.Elective joint arthroplasties for patients in recovery period of SARS-CoV-2 infection could be continued under comprehensive preoperative evaluation and appropriate medical protection. For patients with currently confirmed or highly suspected COVID-19, the operation should be carried out only if it was essential.


Subject(s)
Arthroplasty, Replacement, Hip , COVID-19/transmission , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Medical Staff, Hospital , Perioperative Care/methods , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/adverse effects , Clinical Protocols , Female , Hip/diagnostic imaging , Humans , Male , Middle Aged , Pandemics , Personal Protective Equipment , Postoperative Care , Postoperative Complications , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Workflow
11.
Sci Rep ; 11(1): 13971, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301179

ABSTRACT

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.


Subject(s)
COVID-19/epidemiology , COVID-19/immunology , Coinfection/epidemiology , Genomics , Immunity, Innate , Mutation , SARS-CoV-2/genetics , Adult , COVID-19/transmission , Cytidine Deaminase/genetics , Female , Gene Expression Profiling , Genome, Viral/genetics , Humans , Male , Middle Aged , Nasopharynx/virology , Organ Specificity , SARS-CoV-2/immunology
12.
Front Genet ; 12: 663098, 2021.
Article in English | MEDLINE | ID: covidwho-1268247

ABSTRACT

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.

13.
Finance Research Letters ; : 102133, 2021.
Article in English | ScienceDirect | ID: covidwho-1230487

ABSTRACT

This study examines the impact of COVID-19 on firm innovation using the data of Chinese listed companies from January 2020 to October 2020. The results show that at the national level, COVID-19 inhibits firm innovation in China. At the regional level, there are no differences in the impacts of COVID-19 on Hubei province and other regions. At the firm level, compared with non-state-owned enterprises (NSOEs), COVID-19 has a greater negative effect on the innovation quality of state-owned enterprises (SOEs). Innovation in large companies is more vulnerable to COVID-19 than in small and medium-sized enterprises (SMEs).

14.
Infect Dis Poverty ; 10(1): 31, 2021 Mar 18.
Article in English | MEDLINE | ID: covidwho-1140517

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. METHODS: Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. DISCUSSION: Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. TRIAL REGISTRATION: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).


Subject(s)
COVID-19/complications , COVID-19/virology , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/therapy , SARS-CoV-2 , Antiviral Agents/therapeutic use , Combined Modality Therapy , Data Analysis , Medicine, Chinese Traditional , Pulmonary Fibrosis/diagnosis , Quality of Life , Treatment Outcome
15.
Intensive Care Med Exp ; 9(1): 13, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1133613

ABSTRACT

PURPOSE: Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients. METHODS: In addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples. RESULTS: Obvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein-metabolite-lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes. CONCLUSIONS: This study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis. TAKE HOME MESSAGE: Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration.

16.
Front Med (Lausanne) ; 8: 585358, 2021.
Article in English | MEDLINE | ID: covidwho-1116697

ABSTRACT

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.

19.
Current Issues in Tourism ; : 1-19, 2021.
Article in English | Taylor & Francis | ID: covidwho-1030985
20.
Preprint | SciFinder | ID: ppcovidwho-4225

ABSTRACT

A review. Patients with low immune function are prone to novel coronavirus infection, which is consistent with the traditional Chinese medicine (TCM) concept of deficiency of vital Qi and invasion of toxin. At present, it is necessary to focus on the development of antiviral drugs, but it is also urgent to study the preparation for regulating the immune system. Mucosal tissue is an important barrier of human immune system. It has an independent immune system with unique functions and structures. It is the body′s first line of defense against infection, and is in direct contact with external antigens (such as food, symbiotic bacteria, viruses, etc.). In the resistance to viruses and infections, the mucosal immune system (such as respiratory mucosa, intestinal mucosa, etc.) plays an extremely important role, which can eliminate foreign pathogenic microorganisms or other foreign antigens, so that the virus does not invade the body tissue and cause damage to the body. There are more and more reports on the therapeutic effects of TCM through the mucosal immune system. This paper aims to explore the relationship between mucosal immunity and novel coronavirus pneumonia (COVID-19) and the intervention mechanism of TCM, so as to provide useful research methods and therapeutic ideas for the prevention and treatment of COVID-19.

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