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1.
Microbiol Spectr ; 10(1): e0236221, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1705650

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19). However, the long-term health consequences of COVID-19 are not fully understood. We aimed to determine the long-term lung pathology and blood chemistry changes in Syrian hamsters infected with SARS-CoV-2. Syrian hamsters (Mesocricetus auratus) were inoculated with 105 PFU of SARS-CoV-2, and changes post-infection (pi) were observed for 20 days. On days 5 and 20 pi, the lungs were harvested and processed for pathology and viral load count. Multiple blood samples were collected every 3 to 5 days to observe dynamic changes in blood chemistry. Infected hamsters showed consistent weight loss until day 7 pi At day 5 pi, histopathology of the lungs showed moderate to severe inflammation and the virus could be detected. These results indicate that SARS-CoV-2 has an acute onset and recovery course in the hamster infection model. During the acute onset, blood triglyceride levels increased significantly at day 3 pi During the recovery course, uric acid and low-density lipoprotein levels increased significantly, but the total protein and albumin levels decreased. Together, our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. IMPORTANCE COVID-19 is now considered a multiorgan disease with a wide range of manifestations. There are increasing reports of persistent and long-term effects after acute COVID-19, but the long-term health consequences of COVID-19 are not fully understood. This study reported for the first time the use of blood samples collected continuously in a SARS-CoV-2-infected hamster model, which provides more information about the dynamic changes in blood biochemistry during the acute and recovery phases of SARS-CoV-2 infection. Our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. The study may be used by several researchers and clinicians, especially those who are studying potential treatments for patients with post-acute COVID-19 syndrome.


Subject(s)
COVID-19/complications , SARS-CoV-2/physiology , Animals , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Cricetinae , Disease Models, Animal , Humans , Lipoproteins, LDL/blood , Lung/immunology , Lung/pathology , Lung/virology , Male , Mesocricetus , Uric Acid/blood
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312202

ABSTRACT

Background: Previous studies have documented the clinical characteristics of patients with Coronavirus disease 2019(COVID-19) and presented evidence of person-to-person transmission. Limited data are available for patients with asymptomatic infections. Some asymptomatic carriers, whom we characterize as “exposers” or “infectors”, may be responsible for family clustering of COVID-19. Methods: : A questionnaire survey and follow-up survey based on media reports were used to assess familial clustering of SARS-CoV-2 infection induced by asymptomatic exposers/infectors. Individual data were collected for all members of each tracked family. A transmission map was then drawn for each family. Results: : Our study of 5 families indicated that individuals with no obvious symptoms of COVID-19, regardless of the PCR results, transmitted the virus to other family members who were community contained at home and had no contact with other infected individuals. There was one death case in Family No.3. Conclusion: Asymptomatic exposers/infectors of SARS-CoV-2 were all middle-aged (average age: 44.4 ± 14.9 years) who had no symptoms but had the ability to disseminate the virus. Medical staff participating in treatment of COVID-19 cases all had a high risk of infection, they should be quarantined so as to protect their families. The morbidity and mortality of Case 3.2 remind us that although these asymptomatic infected people have no symptoms, they are also infectious. It is not ruled out that the subsequent infected people are seriously ill or even die. Therefore, we should not take it lightly.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315661

ABSTRACT

Background: Qingfei Paidu decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. This study aims to identify the main constituents in QFPDD and the absorbed components (including prototypes and metabolites) in serum and tissues after oral administration of QFPDD to mice. Methods: : A practical and sensitive method of UHPLC-Q-Exactive-Orbitrap HRMS was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. Results: : A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. Conclusions: : An UHPLC-Q-Orbitrap HRMS based method was established for chemical profiling the constituents in QFPDD, while the absorbed prototypes and metabolites occurring in mice serum and tissues were investigated following oral administration of QFPDD. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

4.
EMBO Mol Med ; 14(4): e15298, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1675333

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.


Subject(s)
COVID-19 , Animals , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Pandemics , RNA, Small Interfering/genetics , SARS-CoV-2/genetics
5.
Nat Med ; 26(6): 845-848, 2020 06.
Article in English | MEDLINE | ID: covidwho-1641979

ABSTRACT

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.


Subject(s)
Antibodies, Viral/blood , Antibody Formation/drug effects , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Antibody Formation/immunology , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2
6.
Brain ; 2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1594202

ABSTRACT

There is growing evidence that severe acute respiratory syndrome coronavirus 2 can affect the CNS. However, data on white matter and cognitive sequelae at the one-year follow-up are lacking. Therefore, we explored these characteristics in this study. We investigated 22 recovered coronavirus disease 2019 (COVID-19) patients and 21 matched healthy controls. Diffusion tensor imaging, diffusion kurtosis imaging and neurite orientation dispersion and density imaging were performed to identify white matter changes, and the subscales of the Wechsler Intelligence scale were used to assess cognitive function. Correlations between diffusion metrics, cognitive function, and other clinical characteristics were then examined. We also conducted subgroup analysis based on patient admission to the intensive care unit. The corona radiata, corpus callosum and superior longitudinal fasciculus had lower volume fraction of intracellular water in the recovered COVID-19 group than in the healthy control group. Patients who had been admitted to the intensive care unit had lower fractional anisotropy in the body of the corpus callosum than those who had not. Compared with the healthy controls, the recovered COVID-19 patients demonstrated no significant decline in cognitive function. White matter tended to present with fewer abnormalities for shorter hospital stays and longer follow-up times. Lower axonal density was detected in clinically recovered COVID-19 patients after one year. Patients who had been admitted to the intensive care unit had slightly more white matter abnormalities. No significant decline in cognitive function was found in recovered COVID-19 patients. The duration of hospital stay may be a predictor for white matter changes at the one-year follow-up.

7.
Neural Regen Res ; 17(7): 1576-1581, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1575953

ABSTRACT

Although some short-term follow-up studies have found that individuals recovering from coronavirus disease 2019 (COVID-19) exhibit anxiety, depression, and altered brain microstructure, their long-term physical problems, neuropsychiatric sequelae, and changes in brain function remain unknown. This observational cohort study collected 1-year follow-up data from 22 patients who had been hospitalized with COVID-19 (8 males and 11 females, aged 54.2 ± 8.7 years). Fatigue and myalgia were persistent symptoms at the 1-year follow-up. The resting state functional magnetic resonance imaging revealed that compared with 29 healthy controls (7 males and 18 females, aged 50.5 ± 11.6 years), COVID-19 survivors had greatly increased amplitude of low-frequency fluctuation (ALFF) values in the left precentral gyrus, middle frontal gyrus, inferior frontal gyrus of operculum, inferior frontal gyrus of triangle, insula, hippocampus, parahippocampal gyrus, fusiform gyrus, postcentral gyrus, inferior parietal angular gyrus, supramarginal gyrus, angular gyrus, thalamus, middle temporal gyrus, inferior temporal gyrus, caudate, and putamen. ALFF values in the left caudate of the COVID-19 survivors were positively correlated with their Athens Insomnia Scale scores, and those in the left precentral gyrus were positively correlated with neutrophil count during hospitalization. The long-term follow-up results suggest that the ALFF in brain regions related to mood and sleep regulation were altered in COVID-19 survivors. This can help us understand the neurobiological mechanisms of COVID-19-related neuropsychiatric sequelae. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University (approval No. 2020S004) on March 19, 2020.

8.
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.


Subject(s)
Atlases as Topic , Single-Cell Analysis/veterinary , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Birds , Cell Communication , Evolution, Molecular , Gene Regulatory Networks , Host-Pathogen Interactions , Lung/cytology , Lung/metabolism , Lung/virology , Mammals , Receptors, Virus/genetics , Receptors, Virus/metabolism , Reptiles , SARS-CoV-2/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Transcriptome , Viral Tropism , Virus Internalization
9.
Psychol Res Behav Manag ; 14: 1889-1900, 2021.
Article in English | MEDLINE | ID: covidwho-1551374

ABSTRACT

OBJECTIVE: To explore the sleep quality and depression-anxiety-stress state of frontline nurses in high-risk areas who conduct nucleic acid sampling testing for COVID-19 to provide a basis for formulating intervention programs in crisis management. METHODS: From August 22 to 30, 2021, a convenient sampling method was used in Zhangjiajie City, Hunan Province, China. A total of 248 frontline nurses who performed nucleic acid sample collection were selected. The following tests were used: the general information questionnaire, Pittsburgh Sleep Quality Questionnaire (PSQI), and Depression-Anxiety Stress Scale (DASS-21). RESULTS: A total of 236 nurses completed the survey; 88.14% (n = 208) were women, the average age was 33.02±6.81, the PSQI score was 15 (13-17), and 231 (97.88%) nurses had sleep disorders during the period in Zhangjiajie, 219 nurses (81.36%) had anxiety, 135 nurses (45.76%) had depression, and 112 nurses (42.59%) felt stressed. Spearman correlation analysis was used to associate the PSQI with the DASS-21. The results showed that the use of hypnotic drugs was negatively correlated with DASS-21 (P<0.05), while the rest were positively correlated. The results of the multivariate analysis of sleep disorders showed that depression, anxiety, and stress were related to sleep quality (P<0.05), and there was no statistical difference in the other variables. CONCLUSION: During the COVID-19 pandemic, the sleep quality and depression-anxiety-stress state of the frontline nurses performing nucleic acid testing were adversely affected. Sleep disturbance is a serious problem among nurses testing for the delta strain during the pandemic. Anxiety, stress, and depression are associated with sleep disorders. It is necessary to take corresponding measures and conduct crisis management interventions to improve sleep quality and mental health adjustment during public health emergencies.

10.
Infect Drug Resist ; 14: 5035-5040, 2021.
Article in English | MEDLINE | ID: covidwho-1547064

ABSTRACT

The patient had several close contacts with friends from Wuhan, the epicenter of the epidemic. His mother and father had close contact with him. His father was later diagnosed with COVID-19 infection after a positive reverse transcription PCR test for SARS-CoV-2 RNA. The patient and his mother were diagnosed as suspected cases of COVID-19 based on a history of exposure, clinical manifestation, and imaging examination. However, the patient was tested more than three times with the reverse transcription PCR test for SARS-CoV-2 RNA, and the results were negative each time. COVID-19 should be suspected, regardless of SARS-CoV-2 test negativity, for recent close contact with a confirmed case and respiratory symptoms.

11.
Acta Cardiol Sin ; 37(6): 643-647, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1529007

ABSTRACT

BACKGROUND: Emerging evidence has shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with cardiac injury, but it remains unclear whether cardiac injury is mainly caused by direct viral infection or is secondary to SARS-CoV-2-induced cytokine storm. METHODS: Through directly treating cardiomyocytes with S protein, a crucial surface protein of SARS-CoV-2, and indirectly treating cardiomyocytes with S protein-derived human T lymphocyte conditioned medium, we compared the intensities of cardiomyocyte injuries caused by either S protein of the virus or S protein of virus-triggered cytokines. RESULTS: The directly treated cardiomyocytes did not show increasing cell apoptosis. In contrast, cardiomyocytes treated with the supernatant medium of S protein pre-conditioned peripheral blood mononuclear cells showed significantly suppressed viability. In addition, using a cardiovascular disease-specific PCR array, genes associated with hypertrophy, apoptosis, inflammation and angiogenesis were observed to be affected by cytokine stress. CONCLUSIONS: Collectively, we found that SARS-CoV-2-induced heart injury may be mainly through the S protein of the virus enhancing host immune responses instead of the S protein of the virus per se. With regards to clinical application, the strategy for treating COVID-19 should not only focus on anti-viral therapy but also on suppressing over-activated immunity.

12.
Ann Med ; 53(1): 2099-2109, 2021 12.
Article in English | MEDLINE | ID: covidwho-1514452

ABSTRACT

BACKGROUND: Patients appear to maintain sequelae post-coronavirus disease 2019 (COVID-19) affecting daily life and physical health. We investigated the changes in and the effects of pulmonary rehabilitation (PR) on exercise capacity and immunology six months after COVID-19 hospitalization. METHODS: This retrospective cohort reviewed 233 COVID-19 patients admitted from 17 January 2020 to 29 February 2020. Ninety-eight patients who completed 2-week and 6-month follow-ups and tests were included. Among 98 patients, 27 completed at least five sessions of PR at the First Hospital of Changsha, China, during the 6-month convalescence were allocated to the PR group; the reminder who had not performed any PR were assigned to the control group. The primary outcome was the change in six-minute walk distance (6-MWD) between the 2-week and 6-month follow-ups, which was assessed via analysis of covariance with a covariate of propensity score that adjusted for the potential confounders. Secondary outcomes were the changes in 6-MWD, SARS-CoV-2 immunoglobulins, T-lymphocytes and blood chemistry, which were evaluated via paired tests. RESULTS: Participants' ages ranged from 19 to 84 years (M = 47, standard deviation (SD)=15) 45.9% identified as male. During the 6-month convalescence, 6-MWD increased 27.0%, with a mean [95% CI] of 113 [92-134] m (p < .001). SARS-CoV-2 IgG and IgM decreased 33.3% (p = .002) and 43.8% (p = .009), CD4+ T cells increased 7.9% (p = .04), and the majority of blood chemistry significantly changed. The patients in the PR group acquired a greater increase in 6-MWD than those in control (unadjusted, 194 [167-221] m, p < .001; adjusted, 123 [68-181] m, p < .001), dose-responsiveness of PR on 6-MWD was observed (p < .001). No differences in immunity variables and blood chemistry were observed between groups. CONCLUSIONS: These findings suggest PR may be a strategy to promote the improvement of exercise capacity after COVID-19.


Subject(s)
COVID-19/rehabilitation , Convalescence , Exercise , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/psychology , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , SARS-CoV-2 , Young Adult
13.
Ther Adv Respir Dis ; 15: 17534666211049739, 2021.
Article in English | MEDLINE | ID: covidwho-1463196

ABSTRACT

AIM: The aim of this study was to investigate the predictive role of lymphocyte subsets and other laboratory measurements in patients with COVID-19. METHODS: Electronic medical records of adult patients with confirmed diagnosis of COVID-19 from the Shanghai Public Health Clinical Center were reviewed retrospectively to obtain relevant data. RESULTS: The mean age of patients was 40.98 ± 15.95 years, with 58% of the patients being males. The cutoff values at the intensive care unit (ICU) admission, mechanical ventilation, and mortality were CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, and 182), and CD4+ /CD8+ cells (1.4, 1.8, and 1.4). The cutoffs below these values indicate the higher chances of disease progression. Higher CD4+ cell count led to lesser chances for ICU admission [odds ratio (OR) (95% confidence interval (CI): 0.994 (0.991, 0.997); p = 0.0002] and mortality [OR (95% CI): 0.988 (0.979, 0.99); p = 0.001], higher CD8+ count was an independent risk factor for ICU admission. T-cell count positively correlated with total lymphocyte count and platelets, while negatively correlated with D-dimer and lactate dehydrogenase (LDH). Among patients with non-severe COVID-19, median CD8+ T cell, CD4+ T cell, total lymphocyte count, and platelets were 570, 362, 1.45, and 211, respectively, while median values decreased to 149, 106, 0.64, and 172, respectively, in patients with severe COVID-19. CONCLUSION: Lower T lymphocyte subsets were significantly associated with higher admission to ICU, mechanical ventilation, and mortality among patients with COVID-19. A cutoff value of ICU admission, mechanical ventilation, and mortality below CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, 182), and CD4+/CD8+ cells (1.4, 1.8, 1.4) may help identify patients at high risk of disease progression. The continuous evaluation of laboratory indices may help with dismal prognosis and prompt intervention to improve outcomes.


Subject(s)
COVID-19/physiopathology , Intensive Care Units/statistics & numerical data , Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/cytology , Adult , COVID-19/mortality , COVID-19/therapy , China , Disease Progression , Female , Humans , Lymphocyte Count , Male , Middle Aged , Prognosis , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Severity of Illness Index
14.
J Affect Disord ; 296: 126-129, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1433434

ABSTRACT

AIMS: This study aimed to investigate the prevalence of anxiety, depression and PTSD symptoms, and associated risk factors among a large-scale sample of adolescents from China after the pandemic and lockdown. METHOD: A total of 57,948 high school students took part in an online survey from July 13 to 29, 2020. The mental health outcomes included anxiety, depression and PTSD symptoms. Risk factors included negative family relationships, COVID-19 related exposure, and a lack of social support. RESULTS: The prevalence of anxiety, depression and PTSD symptoms was 7.1%, 12.8%, and 16.9%, respectively. COVID-19 related exposure significantly linked to the mental health outcomes (all p < .001). The most important predictors for the mental health outcomes were family relationship and social support (all p < .001). CONCLUSION: The pandemic may have long-term adverse mental health consequences among adolescents. Adverse family relationships and lack of social support could be the major risk factors for the post-pandemic mental health outcomes of adolescents.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Adolescent , Anxiety/epidemiology , China/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Depression/epidemiology , Humans , Pandemics , SARS-CoV-2 , Schools , Stress Disorders, Post-Traumatic/epidemiology , Stress, Psychological , Students
16.
Int J Mol Sci ; 22(18)2021 Sep 13.
Article in English | MEDLINE | ID: covidwho-1409702

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/immunology , Cytokine Release Syndrome/immunology , SARS-CoV-2/immunology , Tumor Necrosis Factor-alpha/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Cardiovascular Diseases/virology , Cell Differentiation , Cell Line , Computational Biology , Coronavirus Nucleocapsid Proteins/metabolism , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Humans , Induced Pluripotent Stem Cells , Myocardium/cytology , Myocardium/immunology , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/virology , Phosphoproteins/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Up-Regulation/immunology , Virus Internalization/drug effects
17.
Transbound Emerg Dis ; 68(5): 2676-2686, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1411003

ABSTRACT

As of 21 April 2020, 176 ASF outbreaks have occurred in China. For each outbreak, an investigation was conducted, including historical data retrieval and traceability of potential contacts. The purpose of this study is to conduct a preliminary analysis of the data obtained from the outbreak investigations, including an investigation of the possible contributing factors of the spread of ASF in China. Based on the epidemic situation and the policies issued, the entire epidemic can be divided into three phases. 71 outbreaks were reported between 3 August 2018 and 17 November 2018; 44 outbreaks between 19 November 2018 and 30 March 2019; and 61 outbreaks between 4 April 2019 and 12 April 2020. Based on the reported outbreaks, the proportional rate of outbreaks in small farms (livestock ≤ 500, 127/168) is significantly higher than that of medium (501 ≤ livestock < 2,000, 14/168; 2001 ≤ livestock ≤ 5,000, 9/168) and large farms (livestock ≥ 5,001, 18/168). The odds of infection related to swill feeding (OR = 2.5, 95% CI, 1.5-4.3) and the mechanical dissemination of vehicles and personnel (OR = 2.7, 95% CI, 1.6-4.5) are significantly higher than those of pigs and pig production transportation. Swill feeding is the major contributing factor for small farms while mechanical dissemination of vehicles and personnel is the major contributing factor for large farms. The average duration from the beginning of the infection to the official outbreak report is gradually decreasing, which means that response speed of industry entities and the animal husbandry and veterinary departments from the beginning of the infection to the outbreak report is gradually increasing. Based on the analysis for ASF outbreaks, some policies and suggestions were put forward, such as improving the biosecurity level of the farms, as well as strengthening the supervision of breeding, transportation and slaughter.


Subject(s)
African Swine Fever Virus , African Swine Fever , Epidemics , Swine Diseases , African Swine Fever/epidemiology , African Swine Fever/prevention & control , Animal Husbandry , Animals , China/epidemiology , Disease Outbreaks/prevention & control , Disease Outbreaks/veterinary , Risk Factors , Swine , Swine Diseases/epidemiology , Swine Diseases/prevention & control
18.
Front Pharmacol ; 12: 720018, 2021.
Article in English | MEDLINE | ID: covidwho-1405426

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe "flu-like" symptoms that can progress to acute respiratory distress syndrome (ARDS), pneumonia, renal failure, and death. From the therapeutic perspective, 3-chymotrypsin-like protein (3CLpro) is a plausible target for direct-acting antiviral agents because of its indispensable role in viral replication. The flavonoid ugonin J (UJ) has been reported to have antioxidative and anti-inflammatory activities. However, the potential of UJ as an antiviral agent remains unexplored. In this study, we investigated the therapeutic activity of UJ against SARS-CoV-2 infection. Importantly, UJ has a distinct inhibitory activity against SARS-CoV-2 3CLpro, compared to luteolin, kaempferol, and isokaempferide. Specifically, UJ blocks the active site of SARS-CoV-2 3CLpro by forming hydrogen bonding and van der Waals interactions with H163, M165 and E166, G143 and C145, Q189, and P168 in subsites S1, S1', S2, and S4, respectively. In addition, UJ forms strong, stable interactions with core pharmacophore anchors of SARS-CoV-2 3CLpro in a computational model. UJ shows consistent anti-inflammatory activity in inflamed human alveolar basal epithelial A549 cells. Furthermore, UJ has a 50% cytotoxic concentration (CC50) and a 50% effective concentration (EC50) values of about 783 and 2.38 µM, respectively, with a selectivity index (SI) value of 329, in SARS-CoV-2-infected Vero E6 cells. Taken together, UJ is a direct-acting antiviral that obstructs the activity of a fundamental protease of SARS-CoV-2, offering the therapeutic potential for SARS-CoV-2 infection.

19.
Int J Med Sci ; 18(12): 2561-2569, 2021.
Article in English | MEDLINE | ID: covidwho-1389722

ABSTRACT

SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells and ferrets, and the results confirmed the strong inhibitory effect of SARS-CoV-2 on the induction of I-IFNs. Moreover, we identified genes that are negatively correlated with IFNB1 expression in vitro and in vivo based on Pearson correlation analysis. We found that SARS-CoV-2 activates numerous intrinsic pathways, such as the circadian rhythm, phosphatidylinositol signaling system, peroxisome, and TNF signaling pathways, to inhibit I-IFNs. These intrinsic inhibitory pathways jointly facilitate the successful immune evasion of SARS-CoV-2. Our study elucidates the underlying mechanism by which SARS-CoV-2 evades the host innate antiviral response in vitro and in vivo, providing theoretical evidence for targeting these immune evasion-associated pathways to combat SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Host-Pathogen Interactions/immunology , Interferon-gamma/metabolism , SARS-CoV-2/immunology , Animals , Bronchi/cytology , COVID-19/virology , Cell Line , Datasets as Topic , Disease Models, Animal , Epithelial Cells , Ferrets , Gene Expression Regulation/immunology , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate , Interferon-gamma/immunology , RNA-Seq , Respiratory Mucosa/cytology , Signal Transduction/genetics , Signal Transduction/immunology
20.
Acta Cardiol Sin ; 37(4): 355-364, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1362731

ABSTRACT

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

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