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1.
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.

2.
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
3.
Chin J Integr Med ; 28(1): 3-11, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1588738

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is a major public health issue. The epidemic is unlikely to be contained until the global launch of safe and effective vaccines that could prevent serious illnesses and provide herd immunity. Although most patients have mild flu-like symptoms, some develop severe illnesses accompanied by multiple organ dysfunction. The identification of pathophysiology and early warning biomarkers of a severe type of COVID-19 contribute to the treatment and prevention of serious complications. Here, we review the pathophysiology, early warning indicators, and effective treatment of Chinese and Western Medicine for patients with a severe type of COVID-19.


Subject(s)
COVID-19 , Humans , SARS-CoV-2
4.
Phytomedicine ; 95: 153784, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1521466

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. PURPOSE: To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. METHODS: We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. RESULTS: After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1ß, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. CONCLUSION: YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.


Subject(s)
COVID-19 , NF-kappa B , Animals , Anti-Inflammatory Agents/pharmacology , Cytokines , Humans , Lipopolysaccharides/pharmacology , Molecular Docking Simulation , NF-kappa B/metabolism , SARS-CoV-2 , Signal Transduction , Tandem Mass Spectrometry
5.
J Evid Based Med ; 14(4): 313-332, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1462829

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , China , Humans , Medicine, Chinese Traditional , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
6.
Microbiol Spectr ; 9(1): e0027321, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1341310

ABSTRACT

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , CD4-Positive T-Lymphocytes , China/epidemiology , Cohort Studies , Female , Humans , Lung/virology , Male , Middle Aged , Prospective Studies , Risk Factors , Viral Load , Whole Genome Sequencing
7.
Front Pharmacol ; 11: 634266, 2020.
Article in English | MEDLINE | ID: covidwho-1110322

ABSTRACT

Background: Yindan Jiedu Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Methods: Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Results: Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group (p = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group (p = 0.0180 and p = 0.0028, respectively). Conclusion: YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.

8.
Open Forum Infect Dis ; 7(5): ofaa169, 2020 May.
Article in English | MEDLINE | ID: covidwho-623975

ABSTRACT

BACKGROUND: There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. METHODS: A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. RESULTS: Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883-0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812-0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768-0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739-0.817; P < .0001), or age (0.656; 95% CI, 0.610-0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. CONCLUSIONS: We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

9.
J Transl Med ; 18(1): 206, 2020 05 20.
Article in English | MEDLINE | ID: covidwho-324357

ABSTRACT

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.


Subject(s)
Coronavirus Infections/diagnosis , Critical Illness , Lymphocytes/pathology , Neutrophils/pathology , Pneumonia, Viral/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Child , Child, Preschool , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/pathology , Disease Progression , Female , History, 21st Century , Humans , Infant , Leukocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Prognosis , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
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