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1.
Personality and Individual Differences Vol 192 2022, ArtID 111589 ; 192, 2022.
Article in English | APA PsycInfo | ID: covidwho-1839183

ABSTRACT

To be or not to be quarantined? That is the question posed by COVID-19 pandemic to almost every resident in the world. Approximately three months after the first application of the COVID-19 lockdown to residents in 17 Asian, African, European, American, and Oceanian countries, we carried out a cross-national survey of 26,266 residents via online platforms such as Sojump and Prolific to investigate their willingness to quarantine and its influencing factors. Findings show that 1) The willingness to quarantine is low in countries with high long-term orientation;2) Females are more willing to be quarantined than males;3) Gender difference on willingness to quarantine is large among people with older age and low education. Theoretical and managerial implications are discussed. Understanding how culture and demographics affect people's willingness to quarantine not only provides insight into how to respond to the current pandemic, but also helps the world prepare for future crises. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

2.
Pathogens ; 11(4):452, 2022.
Article in English | MDPI | ID: covidwho-1785869

ABSTRACT

During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare systems, especially for these designated facilities, is how to safely resume hospital function after these patients have been discharged. Here, we take a designated COVID-19-care facility in Wuhan, China, as an example to share our experience in resuming hospital function while ensuring the safety of patients and medical workers. After more than 1200 patients with COVID-19 infections were discharged in late March, 2020, our hospital resumed function by setting up a three-level hospital infection management system with four grades of risk of exposure. Moreover, we also took measures to ensure the safety of medical personnel in different departments including clinics, wards, and operation rooms. After all patients with COVID-19 infections were discharged, during the five months of regular function from April to September in 2020, no positive cases have been found among more than 40,000 people in our hospital, including hospital staff and patients.

3.
Front Microbiol ; 13: 860851, 2022.
Article in English | MEDLINE | ID: covidwho-1775716

ABSTRACT

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a Betacoronavirus characterized by neurological symptoms and a worldwide prevalence. Although PHEV is one of the earliest discovered porcine coronaviruses, it remains poorly studied. The full-length genome of the earliest PHEV strain collected in 1970 in the United States (PHEV/67 N/US/1970) was determined in October 2020. Using this virus as a prototype, we comparatively analyzed all available PHEV full-length sequences during 1970-2015. In phylogenetic trees based on PHEV full-length or spike glycoprotein open reading frame genomic sequences, PHEV/67 N/US/1970 was sorted into a clade different from that of viruses isolated in the United States in 2015. Intriguingly, United States and Belgium viruses isolated in 2015 and 2005, respectively, revealed multiple deletion mutation patterns compared to the strain PHEV/67 N/US/1970, leading to a truncated or a non-functional NS2A coding region. In addition, the genomic similarity analysis showed a hypervariability of the spike glycoprotein coding region, which can affect at least eight potential linear B cell epitopes located in the spike glycoprotein. This report indicates that PHEVs in the United States underwent a significant genetic drift, which might influence PHEV surveillance in other countries.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325354

ABSTRACT

Background: The antigen and antibody kinetics of SARS-CoV-2 infected patients remains unclear, and the clinical values of the serological test have not been completely elucidated. Methods: A total of 154 serum samples from 13 patients with COVID-19 infection were collected at about three-day intervals during hospitalization. Samples were screened for SARS-CoV-2-specific total antibodies (TAb), IgA, IgM, IgG, and antigen (Ag) using chemiluminescent microparticle immunoassays (CMIA). Results: The overall seroconversion and/or four-fold increase rates of TAb, IgA, IgM, and IgG during hospitalization were 92.31%, 92.31%, 84.62%, and 92.31%, respectively. However, within a week of onset, antibodies were present in <50% of the patients. The combination of “Ag and/or TAb” maintained the positive rate at 81.82% during the first three days after symptom onset and quickly enhanced to 92.31% during 4–6 days after the symptom onset. The seropositive median day of Ag was two days after symptom onset. Among patients who underwent IgM and IgG seroconversion, the seroconversion median days of IgA, TAb, IgM, and IgG were 9.5 days, 10 days, 11 days, and 11.5 days after the symptom onset, respectively. Conclusions: Serological testing, especially virus-specific antigen testing, may be helpful for early identification of suspected patients and asymptomatic infections.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325222

ABSTRACT

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001;Approval Number: P20001/PJ01.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315326

ABSTRACT

Background: Mandatory mask wearing policy for general population in public areas were the most controversial mitigative measure for the coronavirus disease 2019 (COVID-19) pandemic. Thus, it was imperative to investigate its influence on the incidence of face touching behaviors. Methods: Videos displaying mask-wearing and face-touching behaviors of general population in public areas were analyzed. Period before the COVID-19 epidemic were defined as January 2018 to October 2019, and those during the pandemic were from February 2020 to August 2020 in East Asia, and March to August 2020 in Europe and United States (US). Findings: 37 videos (4699 individuals) before the pandemic with 135 videos (8217 individuals) were included. The mask wearing rates all increased significantly during the pandemic. However, the incidence of face touching behaviors maintained. The incidence of eyes, nose and mouth touching behaviors decreased in East Asia and Europe, instead of US. Mask wearing rates was negatively related to incidences of face touching behaviors, especially in East Asia. Surprisingly, when mask wearing rates were >0% and <75%, mask wearing rates was positively related to the incidence of face touching behaviors in East Asia significantly (p=0.017). Interpretation: The incidence of face touching behaviors of general population in public areas was negatively associated with mask wearing rates. However, Mandatory mask wearing polices were risky in population with low adherence to masks, among whom, the face touching behaviors in public areas might increase with mask wearing rates rise. Funding: This study was supported by Guangzhou Science and Technology Project (201904010461).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Clinical Ethics Review Board of the Third Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University. Informed consent was waived according to ethical review of biomedical research involving humans by Order of the National Health and Family Planning Commission of the People’s Republic of China No. 11.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315285

ABSTRACT

Background: To assess the dynamic changes in clinical and CT characteristics of COVID-19 patients with different epidemiology histories. Methods: : Fifty-three discharged COVID-19 patients were enrolled at Beijing Youan Hospital, Capital Medical University, from Jan 21 to Mar 10, 2020. Spearman correlation analysis was performed between CT scores and laboratory indicators. Patients were divided into Wuhan (lived in/or traveled to Wuhan, 30 cases) and nonWuhan group (close contacts or unknown exposure, 23 cases). The CT and laboratory findings were compared between and within groups during the clinical process. Results: : Fever (88.7%), cough (64.2%), fatigue (34%), and abnormal laboratory indicators, including lymphopenia, reduced albumin, albumin/globulin (A/G), and elevated C-reactive protein (CRP), were mainly observed. Subpleural ground-glass opacities (86.8%) were usually detected at admission. The CT scores were highly correlated with lymphocytes, CRP, albumin, and A/G at initial and follow-ups (all p <0.05). Four days after admission, most patients (66.7% Wuhan, 47.8% nonWuhan) showed progression, and the CT scores of Wuhan significantly increased ( p =0.015). Eight days after admission, the vast majority of patients (69.2% Wuhan, 100% nonWuhan , p =0.006) presented improvement, and the CT scores of nonWuhan were significantly lower than Wuhan ( p =0.006). Pneumonia was completely absorbed in most patients 2-4 weeks after discharge. Conclusions: : CT plays a crucial role in early diagnosis and monitoring changes in COVID-19. Lymphocytes, CRP, albumin, and A/G are expected to predict disease severity and prognosis. Viral pathogenicity in non-endemic areas may be weaker than core-infected areas. Lung lesions can disappear around 4 weeks after discharge in most patients.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310882

ABSTRACT

Within one month after the first case occurred in Hainan Province, the number of confirmed cases increased to 168, and there was no increase in nearly three months. As the southernmost province and a famous tourist destination, its frequent economic exchanges and high-intensity movements may affect the spread of epidemic. Therefore, it is of great theoretical and practical significance to examine the spatiotemporal evolution and diffusion pattern of the COVID-19 epidemic in Hainan Province.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311713

ABSTRACT

Background: In many countries, the COVID-19 pandemic is occurring in the middle of flu season. Since the responses to COVID-19 are dramatically different, it is critical to accurately discriminate COVID-19 from seasonal flu and pneumonia caused by other common respiratory pathogens. Methods: : Fifty patients (eight patients with COVID-19, eight with influenza, and 34 with community-acquired pneumonia) were included in our study. Sixteen features, such as clinical symptoms, results of routine blood tests, first reverse transcription-polymerase chain reaction (RT-PCR), and chest CT, were collected. The importance of each feature in discriminating COVID-19 from others was ranked by the random forest algorithm. Models with single or multiple features were evaluated using receiver operating characteristic (ROC) curves, the F1 score, and Matthews correlation coefficient (MCC). Results: : An integrated multi-feature model (RT-PCR, CT features and blood lymphocyte percentage) yielded an area under the ROC curve of 0.97 (95% CI: 0.86 – 1, P < 0.01), an F1 score of 0.81 and an MCC of 0.78 in the training cohort as well as an F1 score of 0.86 and an MCC of 0.85 in the validation set. Conclusion: The developed multivariate model showed better accuracy than the current nucleic acid-based method for the differentiation of COVID-19 from influenza and pneumonia caused by other common respiratory pathogens.

10.
Nat Microbiol ; 7(3): 423-433, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671570

ABSTRACT

Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Young Adult
12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296444

ABSTRACT

The antigen and antibody kinetics of SARS-CoV-2 infected patients remains unclear, and the clinical values of the serological test have not been completely elucidated. A total of 154 serum samples from 13 patients with COVID-19 infection were collected at about three-day intervals during hospitalization. Samples were screened for SARS-CoV-2-specific total antibodies (TAb), IgA, IgM, IgG, and antigen (Ag) using chemiluminescent microparticle immunoassays (CMIA). The overall seroconversion and/or four-fold increase rates of TAb, IgA, IgM, and IgG during hospitalization were 92.31%, 92.31%, 84.62%, and 92.31%, respectively. However, within a week of onset, antibodies were present in <50% of the patients. The combination of “Ag and/or TAb” maintained the positive rate at 81.82% during the first three days after symptom onset and quickly enhanced to 92.31% during 4–6 days after the symptom onset. The seropositive median day of Ag was two days after symptom onset. Among patients who underwent IgM and IgG seroconversion, the seroconversion median days of IgA, TAb, IgM, and IgG were 9.5 days, 10 days, 11 days, and 11.5 days after the symptom onset, respectively. Serological testing, especially virus-specific antigen testing, may be helpful for early identification of suspected patients and asymptomatic infections.

13.
Curr Med Imaging ; 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1533548

ABSTRACT

PURPOSE: To investigate the Computed Tomography (CT) imaging characteristics and dynamic changes of COVID-19 pneumonia at different stages. METHODS: Forty-six patients infected with COVID-19 who had chest CT scans were enrolled, and CT scans were performed 4-6 times with an interval of 2-5 days. RESULTS: At the early stage (n=25), ground glass opacity was presented in 11 patients (11/25 or 44.0%) and ground glass opacity mixed with consolidation in 13 (13/25 or 52.0%) in the lung CT images. At the progressive stage (n=38), ground glass opacity was presented in only one patient (1/38 or 2.6%) and ground glass opacity mixed with consolidation in 33 (33/38 or 86.8%). In the early improvement stage (n=38), the imaging presentation was ground glass opacity alone in three patients (3/38 or 7.9%) and ground glass opacity mixed with consolidation in 34 (34/38 or 89.5%). In the late improvement (absorption) stage (n=33), the primary imaging presentation was ground glass presentation in eight patients (8/33 or 24.2%) and ground glass opacity mixed with consolidation in 23 (23/33 or 69.7%). The lesion reached the peak at 4-16 days after disease onset, and 26 (26/38 or 68.4%) patients reached the disease peak within ten days. Starting from 6 to 20 days after onset, the disease began to be improved, with 30 (30/38 or 78.9%) patients being improved within 15 days. CONCLUSION: COVID-19 pneumonia will progress to the peak stage at a mediate time of seven days and enter the improvement stage at twelve days. Computed tomography imaging of the pulmonary lesion has a common pattern from disease onset to improvement and recovery and provides important information for evaluation of the disease course and treatment effect.

14.
[Unspecified Source]; 2020.
Preprint in English | [Unspecified Source] | ID: ppcovidwho-292770

ABSTRACT

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors.

15.
Brief Bioinform ; 23(1)2022 01 17.
Article in English | MEDLINE | ID: covidwho-1522119

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of deaths around the world. To help contribute to the understanding of crucial knowledge and to further generate new hypotheses relevant to SARS-CoV-2 and human protein interactions, we make use of the information abundant Biomine probabilistic database and extend the experimentally identified SARS-CoV-2-human protein-protein interaction (PPI) network in silico. We generate an extended network by integrating information from the Biomine database, the PPI network and other experimentally validated results. To generate novel hypotheses, we focus on the high-connectivity sub-communities that overlap most with the integrated experimentally validated results in the extended network. Therefore, we propose a new data analysis pipeline that can efficiently compute core decomposition on the extended network and identify dense subgraphs. We then evaluate the identified dense subgraph and the generated hypotheses in three contexts: literature validation for uncovered virus targeting genes and proteins, gene function enrichment analysis on subgraphs and literature support on drug repurposing for identified tissues and diseases related to COVID-19. The major types of the generated hypotheses are proteins with their encoding genes and we rank them by sorting their connections to the integrated experimentally validated nodes. In addition, we compile a comprehensive list of novel genes, and proteins potentially related to COVID-19, as well as novel diseases which might be comorbidities. Together with the generated hypotheses, our results provide novel knowledge relevant to COVID-19 for further validation.


Subject(s)
COVID-19 , Computer Simulation , Models, Biological , Protein Interaction Maps , COVID-19/genetics , COVID-19/metabolism , Humans , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
16.
JAMA ; 323(16): 1582-1589, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453469

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/therapy , Adult , Aged , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Blood Donors , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Critical Illness , Female , Glucocorticoids/therapeutic use , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Methylprednisolone/therapeutic use , Middle Aged , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , SARS-CoV-2
18.
Front Vet Sci ; 8: 687079, 2021.
Article in English | MEDLINE | ID: covidwho-1347366

ABSTRACT

Swine acute diarrhea syndrome (SADS) is a highly contagious infectious disease characterized by acute vomiting and watery diarrhea in neonatal piglets. The causative agent for SADS is the swine acute diarrhea syndrome coronavirus (SADS-CoV), an alphacoronavirus in the family Coronaviridae. Currently, SADS-CoV was identified only in Guangdong and Fujian provinces of China, not in any other regions or countries in the world. To explore the genetic diversity of SADS-CoV isolates, herein we comparatively analyzed 44 full-length genomes of viruses isolated in Guangdong and Fujian provinces during 2017-2019. The spike glycoprotein gene of SADS-CoV strain CH/FJWT/2018 isolated in Fujian province is distinct from that of other viral isolates in either spike glycoprotein gene-based phylogenetic analysis or whole genome-based gene similarity analysis. Moreover, at least 7 predicted linear B cell epitopes in the spike glycoprotein of CH/FJWT/2018 would be affected by amino acid variations when compared with a representative virus isolated in Guangdong province. The spike glycoprotein of coronaviruses determines viral host range and tissue tropism during virus infection via specific interactions with the cellular receptor and also plays critical roles in eliciting the production of neutralizing antibodies. Since SADS-CoVs have a broad cell tropism, the results in this report further emphasize that the spike glycoprotein gene is a pivotal target in the surveillance of SADS-CoV.

19.
EClinicalMedicine ; 38: 101035, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1313066

ABSTRACT

BACKGROUND: Many countries have implemented lockdowns to reduce COVID-19 transmission. However, there is no consensus on the optimal timing of these lockdowns to control community spread of the disease. Here we evaluated the relationship between timing of lockdowns, along with other risk factors, and the growth trajectories of COVID-19 across 3,112 counties in the US. METHODS: We ascertained dates for lockdowns and implementation of various non-pharmaceutical interventions at a county level and merged these data with those of US census and county-specific COVID-19 daily cumulative case counts. We then applied a Functional Principal Component (FPC) analysis on this dataset to generate FPC scores, which were used as a surrogate variable to describe the trajectory of daily cumulative case counts for each county. We used machine learning methods to identify risk factors including the timing of lockdown that significantly influenced the FPC scores. FINDINGS: We found that the first eigen-function accounted for most (>92%) of the variations in the daily cumulative case counts. The impact of lockdown timing on the total daily case count of a county became significant beginning approximately 7 days prior to that county reporting at least 5 cumulative cases of COVID-19. Delays in lockdown implementation after this date led to a rapid acceleration of COVID-19 spread in the county over the first ~50 days from the date with at least 5 cumulative cases, and higher case counts across the entirety of the follow-up period. Other factors such as total population, median family income, Gini index, median age, and within-county mobility also had a substantial effect. When adjusted for all these factors, the timing of lockdowns was the most significant risk factor associated with the county-specific daily cumulative case counts. INTERPRETATION: Lockdowns are an effective way of controlling the spread of COVID-19 in communities. Significant delays in lockdown cause a dramatic increase in the cumulative case counts. Thus, the timing of the lockdown relative to the case count is an important consideration in controlling the pandemic in communities. FUNDING: The study period is from June 2020 to July 2021. Dr. Xuekui Zhang is a Tier 2 Canada Research Chairs (Grant No. 950231363) and funded by Natural Sciences and Engineering Research Council of Canada (Grant No. RGPIN201704722). Dr. Li Xing is funded by Natural Sciences and Engineering Research Council of Canada (Grant Number: RGPIN 202103530). This research was enabled in part by support provided by WestGrid (www.westgrid.ca) and Compute Canada (www.computecanada.ca). The computing resource is provided by Compute Canada Resource Allocation Competitions #3495 (PI: Xuekui Zhang) and #1551 (PI: Li Xing). Dr. Don Sin is a Tier 1 Canada Research Chair in COPD and holds the de Lazzari Family Chair at the Heart Lung Innovation, Vancouver, Canada.

20.
J Virol ; 95(14): e0237420, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1207480

ABSTRACT

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses. IMPORTANCE Multiple coronavirus pandemics have occurred over the last 2 decades. This has highlighted a need to be proactive in the development of therapeutics that can be readily deployed in the case of future coronavirus pandemics. We developed and validated a simplified cell-based assay for the identification of chemical inhibitors of 3CL proteases encoded by a wide range of coronaviruses. This assay is reporter free, does not require specialized biocontainment, and is optimized for performance in high-throughput screening. By testing reported 3CL protease inhibitors against a large collection of 3CL proteases with variable sequence similarity, we identified compounds with broad activity against 3CL proteases and uncovered structural insights into features that contribute to their broad activity. Furthermore, we demonstrated that this assay is suitable for identifying chemical inhibitors of proteases from families other than 3CL proteases.


Subject(s)
COVID-19/enzymology , Coronavirus 3C Proteases , Cysteine Proteinase Inhibitors , SARS-CoV-2/enzymology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Cysteine Proteinase Inhibitors/chemistry , Cysteine Proteinase Inhibitors/pharmacology , HEK293 Cells , Humans
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