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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; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319973

ABSTRACT

Background: The pandemic of Coronavirus disease 2019 (COVID-19) is ongoing globally, which is a big challenge for public health. Alteration of human microbiota had been observed in COVID-19. However, it is unknown how the microbiota is associated with the fatality in COVID-19.Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients recruited in the LOTUS clinical trial (Registration number: ChiCTR2000029308) (including 39 deceased patients), and 95 healthy controls from the same geographic area.Findings: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota. Streptococcus was enriched in recovered patients, whereas potential pathogens, including Candida and Enterococcus, were more abundant in deceased patients. Moreover, the microbiota dominated by Streptococcus was more stable than that dominated by other species. In contrast, the URT microbiota in deceased patients showed a more significant alteration and became more deviated from the norm after admission. The abundance of Streptococcus on admission, particularly that of S. parasanguis, was identified as a strong predictor of fatality by Cox and L1 regularized logistic regression analysis, thus could be used as a potential prognostic biomarker of COVID-19.Interpretation Alteration of the URT microbiota was observed in COVID-19 patients and was associated with the fatality rate. A higher abundance of Streptococcus, especially S. parasanguis, on admission in oropharyngeal swabs predicts a better outcome. The generalization of the results in other populations and underlying mechanisms need further investigations.Trial Registration: Participants were enrolled in ChiCTR2000029308.Funding: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004, 2018ZX10301401), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-2-XX, 2016-I2M-1-014, 2018-I2M-1-003), The Non-profit Central Research Institute Fund of CAMS (2020HY320001, 2019PT310029), Beijing Advanced Innovation Center for Genomics (ICG), and Beijing Advanced Innovation Center for Structural Biology (ICSB).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the Institutional Review Board of Jin Yin-Tan Hospital (KY2020-02.01). Written informed consent was obtained from all patients or their legal representatives if they were too unwell to provide consent.

3.
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.

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.
SSRN; 2021.
Preprint in English | SSRN | ID: ppcovidwho-291806

ABSTRACT

The speed of recovery from supply chain disruption has been identified as the predominant factor in building a resilient supply chain. However, COVID-19, as a rapidly evolving crisis, may challenge this assumption. Infection risk concerns would increase if managers decided to resume production immediately after the shutdown caused by the pandemic. Any incidents of infection may lead to further shutdowns of production lines and undermine firms’ long-term cash flows. Sampling 244 production resumption announcements by Chinese manufacturers in the early COVID-19 crisis (February to March 2020), our analysis shows that investors perceived the earlier production resumptions are with higher risk (indicated by declined stock price). Such concerns were exacerbated by more locally confirmed cases of COVID-19, while less salient for manufacturers with high debts (liquidity pressure). In addition, concerns about risks raised in response to early manufacturers’ resumption of production were found to proliferate overseas, as reflected by the more negative investor reactions seen in 252 US customers of the Chinese manufacturers. This study calls for a reassessment of the current disruption management mindset in response to new disasters and rapidly evolving crises (e.g., COVID-19), and provides theoretical, practical, and policy implications for building resilient supply chains.

6.
Am J Respir Crit Care Med ; 204(12): 1379-1390, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1430274

ABSTRACT

Rationale: Alteration of human respiratory microbiota had been observed in coronavirus disease (COVID-19). How the microbiota is associated with the prognosis in COVID-19 is unclear. Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in patients with COVID-19. Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (including 39 deceased patients) and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for patients with COVID-19. Measurements and Main Results: The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and showed high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections and became more deviated from the norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere patients (lower vs. higher abundance, odds ratio, 7.80; 95% CI, 1.70-42.05). Conclusions: URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for diagnosis and prognosis of respiratory diseases merits further investigation.


Subject(s)
COVID-19/microbiology , COVID-19/mortality , Microbiota , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Adult , Aged , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , SARS-CoV-2
7.
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.

8.
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
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