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1.
Interact Cardiovasc Thorac Surg ; 35(1)2022 06 15.
Article in English | MEDLINE | ID: covidwho-1873917

ABSTRACT

Lung transplants are still limited by the shortage of suitable donor lungs, especially during the coronavirus disease 2019 pandemic. A heterotopic lung transplant (HLTx), as a flexible surgical procedure, can maximize the potential of donor lungs in an emergency, but its widespread use is hindered by difficulties in anastomosis and paucity of outcome data. We performed a retrospective review of 4 patients, each of whom received an HLTxs over 1 year, including 1 left-to-right single HLTx, 2 right-to-left single HLTxs and 1 lobar HLTx (right upper lobe-to-left). The median recipient age was 58.5 years (46-68); 3 patients were male. The postoperative hospital stay was 33 days (30-42). One recipient lived for 10 years and died of bronchiolitis obliterans syndrome; the others were alive with no major morbidity at 12 to 31 months after the operation with a 1-year survival of 100%. The follow-up chest images showed that transplanted lungs could be inflated well and adapted morphologically to fill the thoracic cavity in the short and long term. This study demonstrates that an HLTx is a feasible alternative to a conventional lung transplant in emergency cases and could be considered in selected patients at advanced medical centres.


Subject(s)
Bronchiolitis Obliterans , COVID-19 , Lung Transplantation , Tissue and Organ Procurement , Aged , Female , Humans , Lung , Lung Transplantation/adverse effects , Lung Transplantation/methods , Male , Middle Aged , Retrospective Studies
2.
Vaccines ; 10(6):880, 2022.
Article in English | MDPI | ID: covidwho-1869881

ABSTRACT

The purpose of this study was to preliminarily evaluate the immunogenicity and immune persistence of inactivated SARS-CoV-2 vaccines in PLWH in the real world. We collected blood samples from 132 PLWH aged 18–59 years who were vaccinated with two doses of BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine (SinoVac) at 28 ±7 days and 180 ±20 days the after second dose, to detect the level of Spike receptor binding domain-protein specific IgG (S-RBD-IgG) by using chemiluminescence. We found that the BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody seropositivity rates and levels in PLWH than in healthy controls (HCs). The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower humoral immune responses in PLWH, having lower CD4+T cell counts (<350 cells/μL) compared to PLWH, and having higher CD4+T cell counts (≥350 cells/μL) after a second dose of vaccination. The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody levels in PLWH, having CD4+T cell counts ≥350 cells/μL compared to HCs. No negative effects were observed in terms of the CD4+T cell counts and HIV RNA viral load (VL) of PLWH after vaccination. Ninety-nine PLWH and eighty-three HCs completed a second blood collection for testing;we found a statistically significant decrease in the humoral immune response both in PLWH and HCs from 28 days to 180 days after a second dose of BBIBP-CorV vaccine or CoronaVac vaccine. The S-RBD-IgG antibody induced by the BBIBP-CorV vaccine or the CoronaVac vaccine declined faster in the PLWH population than in the healthy population, and two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine may not be enough to provide PLWH with persistent immunity against SARS-CoV-2. It is necessary for PLWH to be prioritized for a third dose over the healthy population, but the immunogenicity of the third dose of the homologous or heterologous vaccine requires further study.

3.
Comput Struct Biotechnol J ; 20: 2442-2454, 2022.
Article in English | MEDLINE | ID: covidwho-1850921

ABSTRACT

Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

4.
Zool Res ; 43(3): 457-468, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1836354

ABSTRACT

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.


Subject(s)
COVID-19 , Lung Injury , Rodent Diseases , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/veterinary , Endothelial Cells , Histamine Antagonists/therapeutic use , Inflammation/drug therapy , Inflammation/etiology , Inflammation/veterinary , Lung Injury/drug therapy , Lung Injury/veterinary , Mice , Rodent Diseases/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
PLoS One ; 17(3): e0264534, 2022.
Article in English | MEDLINE | ID: covidwho-1793513

ABSTRACT

The lessening of food wastage, specifically among nations where about half of its worldwide quantity is produced, has turned to be a mammoth challenge for environmental, social and economic sustainability, and represents one of the seventeen Sustainable Development Goals (SDG) within the Agenda 2030. The quantity of food being thrown away in spite of being in an edible condition has become alarming in middle and high income countries. The COVID-19 lockdown strategy, both at local and international levels, has expressively altered work, life and food consumption behaviors globally, directing to food wastage as a multi sectoral issue. Pakistan has no exception to such manifestations. The main objective of this study is to analyze the perceptions of rural people of Pakistan regarding food wastage during the COVID-19 pandemic. To evaluate whether behavior about food wastage among rural households varied or not during the pandemic, a descriptive survey was carried out using a self-administered questionnaire and 963 responses were selected for further empirical investigations. The findings of the study reveal that food waste actually decreased in spite of an increased amount of purchased food during the lockdown. Our results highlight that the effect of the pandemic has led to reduction in food wastage among rural respondents, an increased consciousness for the morals of food waste, and awareness of environmental impacts of food wastage. The conclusions of this study highlight that rural consumers of Pakistan are emerging with a new level of responsiveness about food wastage with possible positive impact on the environment in terms of decreased greenhouse gas (GHG) emission and other pollutants. The study findings imply that this pandemic time provides a suitable window to raise awareness about food wastage among rural as well as urban households while contemplating effective strategies to overcome the issue of food wastage in the country.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control , Consumer Behavior , Food Security , Refuse Disposal , Adult , Consumer Behavior/statistics & numerical data , Female , Food/statistics & numerical data , Food Security/statistics & numerical data , Food Supply/statistics & numerical data , History, 21st Century , Humans , Male , Pakistan/epidemiology , Pandemics , Perception/physiology , Refuse Disposal/statistics & numerical data , Rural Population/statistics & numerical data , Surveys and Questionnaires
6.
PLoS Pathog ; 18(3): e1010366, 2022 03.
Article in English | MEDLINE | ID: covidwho-1793485

ABSTRACT

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.


Subject(s)
Kynurenine 3-Monooxygenase , Virus Diseases , Animals , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Interferon Regulatory Factor-3/metabolism , Kynurenine/metabolism , Kynurenine 3-Monooxygenase/metabolism , Mice , Quinolinic Acid/metabolism , Quinolinic Acid/pharmacology , Virus Diseases/drug therapy
7.
BMJ Open ; 12(3): e055880, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-1765125

ABSTRACT

IntroductionSilent cerebrovascular disease (SCD), which is a common disease in the elderly, leads to cognitive decline, gait disorders, depression and urination dysfunction, and increases the risk of cerebrovascular events. Our study aims to compare the accuracy of the diagnosis of SCD-related gait disorders between the intelligent system and the clinician. Our team have developed an intelligent evaluation system for gait. This study will evaluate whether the intelligent system can help doctors make clinical decisions and predictions, which aids the early prevention and treatment of SCD. METHODS AND ANALYSIS: This study is a multi-centred, prospective, randomised and controlled trial.SCD subjects aged 60-85 years in Shanghai and Guizhou will be recruited continuously. All subjects will randomly be divided into a doctor with intelligence assistance group or a doctor group, at a 1:1 ratio. The doctor and intelligent assistant group will accept the intelligent system evaluation. The intelligent system obtains gait parameters by an Red-Green-Blue-depth camera and computer vision algorithm. The doctor group will accept the clinicians' routine treatment procedures. Meanwhile, all subjects will accept the panel's gait assessment and recognition rating scale as the gold standard. The primary outcome is the sensitivity of the intelligent system and clinicians to screen for gait disorders. The secondary outcomes include the healthcare costs and the incremental cost effectiveness ratio of intelligent systems and clinicians to screen for gait disorders. ETHICS AND DISSEMINATION: Approval was granted by the Ethics Committee of Zhongshan Hospital affiliated with Fudan University on 26 November 2019. The approval number is B2019-027(2) R. All subjects will sign an informed consent form before enrolment. Serious adverse events will be reported to the main researchers and ethics committees. The subjects' data will be kept strictly confidential. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04457908.


Subject(s)
Cerebrovascular Disorders , Gait , Aged , Cerebrovascular Disorders/diagnosis , China , Cost-Benefit Analysis , Humans , Multicenter Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic
8.
Am J Physiol Lung Cell Mol Physiol ; 322(5): L712-L721, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1759484

ABSTRACT

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Angiotensin-Converting Enzyme 2 , Epithelial Cells , Humans , Lung , Peptidyl-Dipeptidase A , SARS-CoV-2
9.
Int J Environ Res Public Health ; 19(5)2022 03 02.
Article in English | MEDLINE | ID: covidwho-1715385

ABSTRACT

INTRODUCTION: We aimed to measure the impact of the COVID-19 pandemic on maternal mental health, stratifying on pregnancy status, trimester of gestation, and pandemic period/wave. METHODS: Pregnant persons and persons who delivered in Canada during the pandemic, >18 years, were recruited, and data were collected using a web-based strategy. The current analysis includes data on persons enrolled between 06/2020-08/2021. Maternal sociodemographic indicators, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7), stress) were self-reported. Maternal mental health in pregnant women (stratified by trimester, and pandemic period/wave at recruitment) was compared with the mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models. RESULTS: 2574 persons were pregnant and 626 had already delivered at recruitment. Participants who had delivered had significantly higher mean depressive symptom scores compared to those pregnant at recruitment (9.1 (SD, 5.7) vs. 8.4 (SD, 5.3), p = 0.009). Maternal anxiety (aOR 1.51; 95%CI 1.44-1.59) and stress (aOR 1.35; 95%CI 1.24-1.48) were the most significant predictors of severe maternal depression (EDPS ˃ 13) in pregnancy. CONCLUSION: The COVID-19 pandemic had a significant impact on maternal depression during pregnancy and in the post-partum period. Given that gestational depression/anxiety/stress has been associated with preterm birth and childhood cognitive problems, it is essential to continue following women/children, and develop strategies to reduce COVID-19's longer-term impact.


Subject(s)
COVID-19 , Premature Birth , COVID-19/epidemiology , Child , Female , Humans , Infant, Newborn , Mental Health , Pandemics , Pregnancy , SARS-CoV-2
10.
iScience ; 25(3): 103967, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1699805

ABSTRACT

The outbreak of Coronavirus disease 2019 (COVID-19) throughout the world has caused millions of death, while the dynamics of host responses and the underlying regulation mechanisms during SARS-CoV-2 infection are not well depicted. Lung tissues from a mouse model sensitized to SARS-CoV-2 infection were serially collected at different time points for evaluation of transcriptome, proteome, and phosphoproteome. We showed the ebb and flow of several host responses in the lung across the viral infection. The signaling pathways and kinases regulating networks were alternated at different phases of infection. This multiplex evaluation also revealed that many kinases of the CDK and MAPK family were interactive and served as functional hubs in mediating the signal transduction during SARS-CoV-2 infection. Our study not only revealed the dynamics of lung pathophysiology and their underlying molecular mechanisms during SARS-CoV-2 infection, but also highlighted some molecules and signaling pathways that might guide future investigations on COVID-19 therapies.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306694

ABSTRACT

Background: Mental health regional differences during pregnancy through the COVID-19 pandemic are understudied. The first phase of CONCEPTION cohort aims to compare country-specific mental health status in pregnant women following the start of the pandemic.Methods: Pregnant women, >18 years were recruited, and data collected using a web-based strategy. Although Canadian women were primarily targeted, pregnant women worldwide were eligible. The current analysis includes data on women enrolled between 06/2020-11/2020. Self-reported data included COVID-19 testing/diagnosis, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7)), prenatal care/birth plan changes. We compared maternal mental health stratifying on country/continents of residence;and identified determinants of mental health with multivariable linear regression models.Findings: Of 2,109 pregnant women recruited (mean gestational age, 24·7 weeks (SD 9·7)), 1,932 were from Canada, 48 the United States (US), 73 Europe, 35 Africa, and 21 Asia/Oceania. Among the 226 pregnant women who were tested for SARS-CoV-2, 26 were positive (11·5% test positivity rate);COVID-19 prevalence was 1·2% (26/2,109). Mean depressive symptom scores were lower in Canada (EPDS 8·2, SD 5·2) compared to the US (EPDS 10·5, SD 4·8) and Europe (EPDS 10·4, SD 6·5) (p<0·05). Maternal anxiety, stress, decreased income and access to health care due to the pandemic were independently increasing maternal depression. Mean anxiety symptoms were higher in the US (GAD-7 6·5, SD 4·3) than Canada (GAD-7 4·3, SD 3·8) (p<0·05). Maternal depression, stress, and earlier recruitment during the pandemic were independently associated with increased maternal anxiety.Interpretation: In this first international study on the impact of the COVID-19 pandemic, CONCEPTION has shown significant country/continent-specific variations in depression and anxiety during pregnancy. Given that gestational depression/anxiety have been associated with preterm birth and childhood cognitive problems, strategies are needed to reduce COVID-19’s mental health burden. Funding: Faculty of Pharmacy, Université de Montréal, Canada.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: This study was approved by the CHU Sainte-Justine's Research Ethics Committee, which autorized worldwide recruitment of subjects.

12.
Cell ; 185(7): 1117-1129.e8, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1682965

ABSTRACT

Game animals are wildlife species traded and consumed as food and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1,941 game animals, representing 18 species and five mammalian orders, sampled across China. From this, we identified 102 mammalian-infecting viruses, with 65 described for the first time. Twenty-one viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high-risk viruses. We inferred the transmission of bat-associated coronavirus from bats to civets, as well as cross-species jumps of coronaviruses from bats to hedgehogs, from birds to porcupines, and from dogs to raccoon dogs. Of note, we identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence.


Subject(s)
Animals, Wild/virology , Communicable Diseases, Emerging/virology , Disease Reservoirs , Mammals/virology , Virome , Animals , China , Phylogeny , Zoonoses
13.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: covidwho-1594013

ABSTRACT

The ongoing SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2 pandemic has exposed major gaps in our knowledge on the origin, ecology, evolution, and spread of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV) is a member of the genus Alphacoronavirus in the family Coronaviridae that may have originated from bats and leads to significant hazards and widespread epidemics in the swine population. The role of local and global trade of live swine and swine-related products in disseminating PEDV remains unclear, especially in developing countries with complex swine production systems. Here, we undertake an in-depth phylogeographic analysis of PEDV sequence data (including 247 newly sequenced samples) and employ an extension of this inference framework that enables formally testing the contribution of a range of predictor variables to the geographic spread of PEDV. Within China, the provinces of Guangdong and Henan were identified as primary hubs for the spread of PEDV, for which we estimate live swine trade to play a very important role. On a global scale, the United States and China maintain the highest number of PEDV lineages. We estimate that, after an initial introduction out of China, the United States acted as an important source of PEDV introductions into Japan, Korea, China, and Mexico. Live swine trade also explains the dispersal of PEDV on a global scale. Given the increasingly global trade of live swine, our findings have important implications for designing prevention and containment measures to combat a wide range of livestock coronaviruses.


Subject(s)
Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , China , Pandemics , Phylogeny , Phylogeography , Porcine epidemic diarrhea virus/genetics , Swine , Swine Diseases/epidemiology , United States
14.
Viruses ; 13(11)2021 11 08.
Article in English | MEDLINE | ID: covidwho-1512697

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2. In this study, we summarized the current findings on the optimized sACE2-based strategies as a therapeutic agent, including Fc fusion to prolong the half-life of sACE2, deep mutagenesis to create high-affinity decoys for SARS-CoV-2, or designing the truncated functional fragments to enhance its safety, among others. Considering that COVID-19 patients are often accompanied by manifestations of cardiovascular complications, we think that administration of sACE2 in COVID-19 patients may be a promising therapeutic strategy to simultaneously treat both cardiovascular diseases and SARS-CoV-2 infection. This review would provide insights for the development of novel therapeutic agents against the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Cardiovascular Diseases/drug therapy , Recombinant Fusion Proteins/therapeutic use , SARS-CoV-2 , Animals , COVID-19/complications , Cardiovascular Diseases/complications , Humans , Peptidyl-Dipeptidase A , Protein Binding , Protein Engineering , Receptors, Virus/metabolism , Receptors, Virus/therapeutic use , Spike Glycoprotein, Coronavirus
15.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750488

ABSTRACT

The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.

16.
Pathogens ; 10(10)2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1480900

ABSTRACT

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China. Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were "mixing vessel" for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.

18.
JMIR Public Health Surveill ; 7(10): e31125, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1430625

ABSTRACT

BACKGROUND: HIV infection is a significant independent risk factor for both severe COVID-19 presentation at hospital admission and in-hospital mortality. Available information has suggested that people living with HIV and AIDS (PLWHA) could benefit from COVID-19 vaccination. However, there is a dearth of evidence on willingness to receive COVID-19 vaccination among PLWHA. OBJECTIVE: The aim of this study was to investigate willingness to receive COVID-19 vaccination among a national sample of PLWHA in China. METHODS: This cross-sectional online survey investigated factors associated with willingness to receive COVID-19 vaccination among PLWHA aged 18 to 65 years living in eight conveniently selected Chinese metropolitan cities between January and February 2021. Eight community-based organizations (CBOs) providing services to PLWHA facilitated the recruitment. Eligible PLWHA completed an online survey developed using a widely used encrypted web-based survey platform in China. We fitted a single logistic regression model to obtain adjusted odds ratios (aORs), which involved one of the independent variables of interest and all significant background variables. Path analysis was also used in the data analysis. RESULTS: Out of 10,845 PLWHA approached by the CBOs, 2740 completed the survey, and 170 had received at least one dose of the COVID-19 vaccine. This analysis was performed among 2570 participants who had never received COVID-19 vaccination. Over half of the participants reported willingness to receive COVID-19 vaccination (1470/2570, 57.2%). Perceptions related to COVID-19 vaccination were significantly associated with willingness to receive COVID-19 vaccination, including positive attitudes (aOR 1.11, 95% CI 1.09-1.12; P<.001), negative attitudes (aOR 0.96, 95% CI 0.94-0.97; P<.001), perceived support from significant others (perceived subjective norm; aOR 1.53, 95% CI 1.46-1.61; P<.001), and perceived behavioral control (aOR 1.13, 95% CI 1.11-1.14; P<.001). At the interpersonal level, receiving advice supportive of COVID-19 vaccination from doctors (aOR 1.99, 95% CI 1.65-2.40; P<.001), CBO staff (aOR 1.89, 95% CI 1.51-2.36; P<.001), friends and/or family members (aOR 3.22, 95% CI 1.93-5.35; P<.001), and PLWHA peers (aOR 2.38, 95% CI 1.85-3.08; P<.001) was associated with higher willingness to receive COVID-19 vaccination. The overall opinion supporting COVID-19 vaccination for PLWHA on the internet or social media was also positively associated with willingness to receive COVID-19 vaccination (aOR 1.59, 95% CI 1.31-1.94; P<.001). Path analysis indicated that interpersonal-level variables were indirectly associated with willingness to receive COVID-19 vaccination through perceptions (ß=.43, 95% CI .37-.51; P<.001). CONCLUSIONS: As compared to PLWHA in other countries and the general population in most parts of the world, PLWHA in China reported a relatively low willingness to receive COVID-19 vaccination. The internet and social media as well as interpersonal communications may be major sources of influence on PLWHA's perceptions and willingness to receive COVID-19 vaccination.


Subject(s)
COVID-19 , HIV Infections , COVID-19 Vaccines , China/epidemiology , Cross-Sectional Studies , Humans , SARS-CoV-2 , Vaccination
19.
Huan Jing Ke Xue ; 42(9): 4126-4139, 2021 Sep 08.
Article in Chinese | MEDLINE | ID: covidwho-1368044

ABSTRACT

To reduce the risks of COVID-19 on society and the health of the general public, necessary prevention and control measures were implemented throughout China in 2020. Consequently, air quality was greatly improved due to lower emissions. However, the improvement of air quality could also be closely related to meteorological conditions. During quarantine (January 27 to February, 2020), reductions were observed in the concentration of all air pollutants in Henan Province (PM2.5, PM10, SO2, CO, and NO2 decreased by 36.89%, 34.18%, 19.43%, 29.85%, and 58.51%, respectively) relative to measurements taken from January 1 to 26, 2020. The only exception was for the concentration of O3, which increased by 69.64%. This study evaluates the importance of meteorological conditions in air pollution, through simulation with a long-and-short-term memory network (LSTM) and a machine learning algorithm. Results show that meteorological conditions play a crucial role in air pollutant formation. Given favorable meteorological factors, the concentrations of pollutants could be reduced by 15%-30%, while the reduction due to anthropogenic emission control ranges from 6%-40%. During the epidemic, meteorological conditions and human emissions accounted for 34.84% and 34.81% of the increase in O3 concentration, respectively. The results show that primary pollutant concentrations are more sensitive to the intensity of anthropogenic emissions. However, secondary pollutants are more dependent on meteorological factors. Furthermore, a nonlinear relationship has been identified between O3 concentration and to emission intensity. Further investigation into the causes of the rise in O3 concentration is necessary to gain a greater understanding and better control of particulate matter and O3 pollution.


Subject(s)
Air Pollution , COVID-19 , Algorithms , Humans , Machine Learning , Pandemics , SARS-CoV-2
20.
Front Pharmacol ; 12: 722511, 2021.
Article in English | MEDLINE | ID: covidwho-1365573

ABSTRACT

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence. Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998-2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations. Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84-2.30), LBW (aOR 1.11, 95%CI 0.59-2.06), or MCM (aOR 1.01, 95%CI 0.67-1.52). Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

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