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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329048

ABSTRACT

Background: The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral-pharynx in the context of SARS-CoV-2 and other viral infections, hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputum, and 152 faecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load;and microbial community in upper respiratory tract renders high risk of antibiotic resistance. Longitudinally, microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

3.
Advanced Engineering Informatics ; 51:101516, 2022.
Article in English | ScienceDirect | ID: covidwho-1588549

ABSTRACT

Transfer learning (TL) is a machine learning (ML) method in which knowledge is transferred from the existing models of related problems to the model for solving the problem at hand. Relational TL enables the ML models to transfer the relationship networks from one domain to another. However, it has two critical issues. One is determining the proper way of extracting and expressing relationships among data features in the source domain such that the relationships can be transferred to the target domain. The other is how to do the transfer procedure. Knowledge graphs (KGs) are knowledge bases that use data and logic to graph-structured information;they are helpful tools for dealing with the first issue. The proposed relational feature transfer learning algorithm (RF-TL) embodies an extended structural equation modelling (SEM) as a method for constructing KGs. Additionally, in fields such as medicine, economics, and law related to people’s lives and property safety and security, the knowledge of domain experts is a gold standard. This paper introduces the causal analysis and counterfactual inference in the TL domain that directs the transfer procedure. Different from traditional feature-based TL algorithms like transfer component analysis (TCA) and CORelation Alignment (CORAL), RF-TL not only considers relations between feature items but also utilizes causality knowledge, enabling it to perform well in practical cases. The algorithm was tested on two different healthcare-related datasets — sleep apnea questionnaire study data and COVID-19 case data on ICU admission — and compared its performance with TCA and CORAL. The experimental results show that RF-TL can generate better transferred models that give more accurate predictions with fewer input features.

4.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
5.
Front Psychiatry ; 12: 769697, 2021.
Article in English | MEDLINE | ID: covidwho-1581158

ABSTRACT

Background: The COVID-19 pandemic is a major public health emergency. However, little is known about the psychological impact of this pandemic on adolescents. We aim to assess the prevalence and influencing factors of depression, anxiety, and posttraumatic growth (PTG) among adolescents in a large sample study. Methods: This cross-sectional study collected demographic data and mental health measurements from 175,416 adolescents covering 31 provinces, centrally administered municipalities, and autonomous regions in mainland China from February 23 to March 8, 2020. The status of depression, anxiety, and PTG was assessed by the nine-item Patient Health Questionnaire, seven-item generalized anxiety disorder questionnaire, and post-traumatic growth inventory. Results: The prevalence of depression, anxiety, and PTG in adolescents was 35.9, 28.0, and 45.6%, respectively. The prevalence of depression and anxiety in the slight or severe epidemic areas was similar. Regression analysis showed that female sex and older age were associated with higher levels of depression, anxiety, and lower levels of PTG. Symptoms related to COVID-19, excessive attention to epidemic information, living in urban or severe epidemic areas, and conflicts with parents during home quarantine were risk factors for depression, anxiety, and PTG. Frequent communication with peers, exercise, and receiving public welfare psychological assistance were protective factors. Poor family economic status was a significant risk factor for depression and PTG. Conclusion: Our findings suggested that positive and negative psychological reactions coexist in adolescents faced with the pandemic. The factors associated with psychological problems and PTG provide strategic guidance for maintaining adolescents' mental health in China and worldwide during any pandemic such as COVID-19.

6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295864

ABSTRACT

The standard practice of presenting one viral sequence for each infected individual implicitly assumes low within-host genetic diversity. It places the emphasis on the viral evolution between, rather than within, hosts. To determine this diversity, we collect SARS-CoV-2 samples from the same patient multiple times. Our own data in conjunction with previous reports show that two viral samples collected from the same individual are often very different due to the substantial within-host diversity. Each sample captures only a small part of the total diversity that is transiently and locally released from infected cells. Hence, the global SARS-CoV-2 population is a meta-population consisting of the viruses in all the infected hosts, each of which harboring a genetically diverse sub-population. Advantageous mutations must be present first as the within-host diversity before they are revealed as between-host polymorphism. The early detection of such diversity in multiple hosts could be an alarm for potentially dangerous mutations. In conclusion, the main forces of viral evolution, i.e., mutation, drift, recombination and selection, all operate within hosts and should be studied accordingly. Several significant implications are discussed.

7.
Clin Infect Dis ; 73(9): e2814-e2817, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501023

ABSTRACT

Intrahost analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences identified 2 viral haplotypes comprised of 3 genetically linked mutations from the respiratory and intestinal tracts of a patient with coronavirus disease 2019. Spatiotemporal data suggest that this patient initially had dual infection of 2 SARS-CoV-2 variants, which subsequently redistributed into the 2 systems.


Subject(s)
COVID-19 , SARS-CoV-2 , Genomics , Humans , Respiratory System
8.
Front Public Health ; 9: 690525, 2021.
Article in English | MEDLINE | ID: covidwho-1436029

ABSTRACT

Background: Understanding the levels of health literacy among different groups is essential for better public health interventions targeting specific subgroups of the population. Additionally, this article explores the prevalence and influencing factors of the health literacy levels of different age groups during the COVID-19 epidemic. Methods: Multistage stratified cluster random sampling and the Probability Proportion to Size (PPS) method were used to select permanent residents aged 15-69 in Chongqing (54,706) for the questionnaire survey. The survey period is from July 2019 and July 2020. Single-factor analysis and logistic regression models were used to study the relationship between demographics, socioeconomic factors, other independent covariates, and health literacy. Results: The health literacy levels of residents declined with age, and there were significant differences in health literacy levels between age groups (χ2 = 3332.884, P < 0.05). As far as the factors affecting health literacy level are concerned, high education and high income are the protective factors for health literacy level for residents of all ages. For adolescents (OR = 1.383, 95% CI: 1.217-1.571), young adults (OR = 1.232, 95% CI = 1.117-1.358), and middle-aged people (OR = 1.096, 95% CI = 1.017-1.182), residence in rural areas was a protective factor. In terms of the dimensions of health literacy, in particular, elderly health literacy in 2020 in Scientific Health Concepts, Safety and First Aid, Basic Medical Care decreased significantly compared with 2019. Conclusions: For adolescents, young adults, middle-aged people, to solve the problem of urban and rural health quality gap, we should not only use the geographical division, but also consider the social population and socio-economic differences. For the elderly, the following four dimensions of health literacy need to be paid more attention than those of other age: Basic Knowledge and Concepts, Scientific Health Concepts, Safety and First Aid, and Basic Medical Care. A lack of knowledge on the prevention and treatment of chronic diseases is the main reason for the recent decline in health literacy. And the health literacy among residents in major public health emergencies is needed.


Subject(s)
COVID-19 , Health Literacy , Adolescent , Aged , China/epidemiology , Humans , Middle Aged , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
9.
Natl Sci Rev ; 8(4): nwab006, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1254806

ABSTRACT

After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.

10.
Virulence ; 12(1): 444-469, 2021 12.
Article in English | MEDLINE | ID: covidwho-1117781

ABSTRACT

Owing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.


Subject(s)
COVID-19/drug therapy , Endoribonucleases/metabolism , RNA, Viral/metabolism , Ribonuclease, Pancreatic/metabolism , Virus Replication/physiology , Eosinophils/metabolism , Humans , Pathogen-Associated Molecular Pattern Molecules/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
11.
Mol Cell ; 80(6): 1123-1134.e4, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-939163

ABSTRACT

Analyzing the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from clinical samples is crucial for understanding viral spread and evolution as well as for vaccine development. Existing RNA sequencing methods are demanding on user technique and time and, thus, not ideal for time-sensitive clinical samples; these methods are also not optimized for high performance on viral genomes. We developed a facile, practical, and robust approach for metagenomic and deep viral sequencing from clinical samples. We demonstrate the utility of our approach on pharyngeal, sputum, and stool samples collected from coronavirus disease 2019 (COVID-19) patients, successfully obtaining whole metatranscriptomes and complete high-depth, high-coverage SARS-CoV-2 genomes with high yield and robustness. With a shortened hands-on time from sample to virus-enriched sequencing-ready library, this rapid, versatile, and clinic-friendly approach will facilitate molecular epidemiology studies during current and future outbreaks.


Subject(s)
COVID-19/genetics , Genome, Viral , High-Throughput Nucleotide Sequencing , RNA, Viral/genetics , SARS-CoV-2/genetics , Whole Genome Sequencing , Animals , Humans , Mice , NIH 3T3 Cells , RNA, Viral/metabolism , SARS-CoV-2/metabolism
12.
Nat Commun ; 11(1): 5503, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894393

ABSTRACT

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Beijing/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Female , Genome, Viral , Genomics , Genotype , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Polymorphism, Single Nucleotide , SARS-CoV-2 , Travel , Young Adult
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