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1.
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.

2.
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
3.
Biomed Signal Process Control ; 69: 102901, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1283954

ABSTRACT

As the COVID-19 virus spreads around the world, testing and screening of patients have become a headache for governments. With the accumulation of clinical diagnostic data, the imaging big data features of COVID-19 are gradually clear, and CT imaging diagnosis results become more important. To obtain clear lesion information from the CT images of patients' lungs is helpful for doctors to adopt effective medical methods, and at the same time, is helpful to screen the patients with real infection. Deep learning image segmentation is widely used in the field of medical image segmentation. However, there are some challenges in using deep learning to segment the lung lesions of COVID-19 patients. Since image segmentation requires the labeling of lesion information on a pixel by pixel basis, most professional radiologists need to screen and diagnose patients on the front line, and they do not have enough energy to label a large amount of image data. In this paper, an improved Dense GAN to expand data set is developed, and a multi-layer attention mechanism method, combined with U-Net's COVID-19 pulmonary CT image segmentation, is proposed. The experimental results showed that the segmentation method proposed in this paper improved the segmentation accuracy of COVID-19 pulmonary medical CT image by comparing with other image segmentation methods.

5.
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.

6.
Int J Infect Dis ; 107: 242-246, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1208961

ABSTRACT

OBJECTIVE: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. METHODS: We applied the Kaplan-Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. MAIN RESULTS: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. CONCLUSION: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Oropharynx/virology , SARS-CoV-2/isolation & purification , Sputum/virology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Young Adult
7.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1165586

ABSTRACT

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.


Subject(s)
Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Antimalarials/therapeutic use , COVID-19 , Chronic Disease , Coronavirus Infections/complications , Drug Combinations , Female , Fever , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Treatment Outcome , Young Adult
8.
Innovation (N Y) ; 2(2): 100099, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-1142304

ABSTRACT

SARS-CoV-2 has caused over 100 million deaths and continues to spread rapidly around the world. Asymptomatic transmission of SARS-CoV-2 is the Achilles' heel of COVID-19 public health control measures. Phylogenomic data on SARS-CoV-2 could provide more direct information about asymptomatic transmission. In this study, using a novel MINERVA sequencing technology, we traced asymptomatic transmission of COVID-19 patients in Beijing, China. One hundred and seventy-eight close contacts were quarantined, and 14 COVID-19 patients were laboratory confirmed by RT-PCR. We provide direct phylogenomic evidence of asymptomatic transmission by constructing the median joining network in the cluster. These data could help us to determine whether the current symptom-based screening should cover asymptomatic persons.

9.
Comput Struct Biotechnol J ; 18: 3518-3527, 2020.
Article in English | MEDLINE | ID: covidwho-927582

ABSTRACT

The outbreak of COVID-19 raises an urgent need for the therapeutics to contain the emerging pandemic. However, no effective treatment has been found for SARS-CoV-2 infection to date. Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2, which was validated by surface plasmon resonance (SPR) assay. Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor. Notably, quercetin could also bind to the RBD domain of S-protein, suggesting not only a receptor blocking, but also a virus neutralizing effect of quercetin on SARS-CoV-2. The results from network pharmacology and bioinformatics analysis support a view that quercetin is involved in host immunomodulation, which further renders it a promising candidate against COVID-19. Moreover, given that puerarin is already an existing drug, results from this study not only provide insight into its action mechanism, but also propose a prompt application of it on COVID-19 patients for assessing its clinical feasibility.

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