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1.
Front Public Health ; 11: 1119163, 2023.
Article in English | MEDLINE | ID: covidwho-2320572

ABSTRACT

Introduction: Breast cancer is the most prevalent malignancy in patients with coronavirus disease 2019 (COVID-19). However, vaccination data of this population are limited. Methods: A cross-sectional study of COVID-19 vaccination was conducted in China. Multivariate logistic regression models were used to assess factors associated with COVID-19 vaccination status. Results: Of 2,904 participants, 50.2% were vaccinated with acceptable side effects. Most of the participants received inactivated virus vaccines. The most common reason for vaccination was "fear of infection" (56.2%) and "workplace/government requirement" (33.1%). While the most common reason for nonvaccination was "worry that vaccines cause breast cancer progression or interfere with treatment" (72.9%) and "have concerns about side effects or safety" (39.6%). Patients who were employed (odds ratio, OR = 1.783, p = 0.015), had stage I disease at diagnosis (OR = 2.008, p = 0.019), thought vaccines could provide protection (OR = 1.774, p = 0.007), thought COVID-19 vaccines were safe, very safe, not safe, and very unsafe (OR = 2.074, p < 0.001; OR = 4.251, p < 0.001; OR = 2.075, p = 0.011; OR = 5.609, p = 0.003, respectively) were more likely to receive vaccination. Patients who were 1-3 years, 3-5 years, and more than 5 years after surgery (OR = 0.277, p < 0.001; OR = 0.277, p < 0.001, OR = 0.282, p < 0.001, respectively), had a history of food or drug allergies (OR = 0.579, p = 0.001), had recently undergone endocrine therapy (OR = 0.531, p < 0.001) were less likely to receive vaccination. Conclusion: COVID-19 vaccination gap exists in breast cancer survivors, which could be filled by raising awareness and increasing confidence in vaccine safety during cancer treatment, particularly for the unemployed individuals.


Subject(s)
Breast Neoplasms , COVID-19 , Cancer Survivors , Humans , Female , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology
2.
Antimicrob Resist Infect Control ; 11(1): 164, 2022 12 24.
Article in English | MEDLINE | ID: covidwho-2286156

ABSTRACT

BACKGROUND: The overuse of antibiotics in primary healthcare settings (PHSs) has caused a serious public health problem in China. The outbreak of the Coronavirus Disease-19 (COVID-19) pandemic brought about dramatic changes in the supply of and demand for medical services in PHSs, possibly resulting in unprecedented changes in antibiotic use. OBJECTIVE: This study aims to assess the immediate and long-term impacts of the COVID-19 pandemic on the changes in antibiotic consumption in PHSs. METHOD: The data on antibiotic consumption were collected from selected township hospitals in Shandong, China from January 2019 to December 2021. Antibiotic consumption was quantified by using the defined daily doses (DDDs) and the WHO Access, Watch, Reserve category. A segmented regression model was established to analyze the immediate and long-term impacts of the COVID-19 pandemic on antibiotic use by using the interrupted time series analysis. RESULTS: The overall antibiotic consumption in all PHSs decreased by 32.04% and 16.69% in 2020 and 2021 respectively compared to the corresponding period in 2019. Over the entire study period, the use of penicillins (J01C) and cephalosporins (J01D) accounted for more than 50% of the total antibiotic consumption. The average annual consumption of Watch category antibiotics decreased by 42.02% and 33.47% in 2020 and 2021 respectively compared to that in 2019. According to the interrupted time series analysis, the total antibiotic consumption decreased significantly immediately after the COVID-19 pandemic outbreak (coef. = - 2.712, p = 0.045), but it then increased significantly over a long-term (coef. = 0.205, p = 0.005). Additionally, the consumption of Access category antibiotics increased significantly in PHSs in the long-term (coef. = 0.136, p = 0.018). However, the consumption of Watch category antibiotics declined sharply immediately after the pandemic (coef. = - 1.222, p < 0.001), but then it increased slightly over a long-term (coef. = 0.073, p < 0.001). CONCLUSION: The extensive use of penicillin and cephalosporins should be of great concern. After the outbreak of COVID-19 pandemic, the total antibiotic consumption decreased generally and the use pattern was improved to some extent in the PHSs in Shandong, China. This provides an opportunity for improving the misuse of antibiotics in PHSs in China.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Humans , Anti-Bacterial Agents/therapeutic use , Pandemics , Drug Utilization , COVID-19/epidemiology , Hospitals , Cephalosporins/therapeutic use , Penicillins , China/epidemiology
3.
J Int Med Res ; 51(2): 3000605231152108, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2235997

ABSTRACT

OBJECTIVES: To investigate associations between oral health and psychological factors (i.e., depression, anxiety, and resilience) in a group of Chinese individuals who had sought an intervention online during the COVID-19 pandemic. METHODS: For this cross-sectional study, online questionnaires were created using online survey software from set items of instruments commonly used to assess depression, anxiety, and resilience combined with an oral health survey. The study was conducted from March 13 to 16, 2020. RESULTS: 568 participants (188 men and 380 women) with a mean ± SD age of 41.7 ± 10.2 years were included in the analyses. In total, 152 (27%) participants were from Beijing, 149 (26%) from Wuhan, 110 (19%) from Shenyang, and 157 (28%) from other Chinese cities. Halitosis and bleeding gums were the most common reasons for individuals to seek an intervention. Compared with other cities, participants from Wuhan showed higher anxiety and depression and worse previous oral health. Resilience mediated the relationship between depression and oral health, but not between anxiety and oral health. CONCLUSION: We hope that the data from this study will inform clinical practitioners and demonstrate that mental health awareness and resilience training are important strategies that may mitigate the negative impact of lockdown and isolation on oral health.


Subject(s)
COVID-19 , Male , Humans , Female , Adult , Middle Aged , COVID-19/epidemiology , Cross-Sectional Studies , SARS-CoV-2 , Pandemics , Oral Health , Communicable Disease Control , Anxiety/epidemiology , Anxiety/psychology , Disease Outbreaks , Surveys and Questionnaires , China/epidemiology , Depression/epidemiology , Depression/psychology
4.
Front Psychol ; 13: 873770, 2022.
Article in English | MEDLINE | ID: covidwho-2099222

ABSTRACT

Objectives: More and more countries have decided to cancel most or even all COVD-19 restrictions. However, it is unclear how ending of restrictions will affect primary care providers' job satisfaction and organizational commitment. Our objectives are to explore the current status and possible change in primary care providers' job satisfaction and organizational commitment after massive restriction policies ended in China. Methods: This was a mixed-method study that utilized structured questionnaires and semi-structured qualitative individual interviews. The 20-item Minnesota Satisfaction Questionnaire (MSQ) and 25-item organizational commitment survey were adopted to assess job satisfaction and organization commitment. Descriptive statistics and mediation models, as well as inductive thematic analysis, were used to analyze quantitative and qualitative data. Results: A total of 18 interviews and 435 valid survey responses were included in our analysis. The average scores for job satisfaction and organizational commitment were 80.6 and 90.8. The thematic analysis revealed one major theme: ethical and moral responsibility to provide care as primary care providers, on which we established a mediation model. The mediation analysis revealed that normative commitment could positively affect the other four dimensions of organizational commitment and job satisfaction. The direct effect of affective commitment on job satisfaction was significant (LLCI = 0.11, ULCI = 0.31), and the mediators were identified to have a partial mediating effect instead of a total mediating effect. Conclusion: After COVID-19 restrictions end, the job satisfaction and organizational commitment of primary care providers will return to levels before the pandemic and during this estimated process, a brief rise in resignation is predictable. The normative commitment positively affects the other four dimensions of organizational commitment and job satisfaction for primary care providers, which suggests a possible way to motivate primary care providers when restrictions end.

5.
Front Microbiol ; 13: 1019444, 2022.
Article in English | MEDLINE | ID: covidwho-2099188

ABSTRACT

Background: The diversity in currently documented viruses and their morphological characteristics indicates the need for understanding the evolutionary characteristics of viruses. Notably, further studies are needed to obtain a comprehensive landscape of virome, the virome of host species in Yunnan province, China. Materials and methods: We implemented the metagenomic next-generation sequencing strategy to investigate the viral diversity, which involved in 465 specimens collected from bats, pangolins, monkeys, and other species. The diverse RNA viruses were analyzed, especially focusing on the genome organization, genetic divergence and phylogenetic relationships. Results: In this study, we investigated the viral composition of eight libraries from bats, pangolins, monkeys, and other species, and found several diverse RNA viruses, including the Alphacoronavirus from bat specimens. By characterizing the genome organization, genetic divergence, and phylogenetic relationships, we identified five Alphacoronavirus strains, which shared phylogenetic association with Bat-CoV-HKU8-related strains. The pestivirus-like virus related to recently identified Dongyang pangolin virus (DYPV) strains from dead pangolin specimens, suggesting that these viruses are evolving. Some genomes showed higher divergence from known species (e.g., calicivirus CS9-Cali-YN-CHN-2020), and many showed evidence of recombination events with unknown or known strains (e.g., mamastroviruses BF2-astro-YN-CHN-2020 and EV-A122 AKM5-YN-CHN-2020). The newly identified viruses showed extensive changes and could be assigned as new species, or even genus (e.g., calicivirus CS9-Cali-YN-CHN-2020 and iflavirus Ifla-YN-CHN-2020). Moreover, we identified several highly divergent RNA viruses and estimated their evolutionary characteristics among different hosts, providing data for further examination of their evolutionary dynamics. Conclusion: Overall, our study emphasizes the close association between emerging viruses and infectious diseases, and the need for more comprehensive surveys.

6.
BMJ Open ; 12(6): e059396, 2022 06 20.
Article in English | MEDLINE | ID: covidwho-1902010

ABSTRACT

INTRODUCTION: The COVID-19 outbreak poses a significant threat to the patients with tuberculosis (TB). TB and COVID-19 (TB-COVID) coinfection means the disease caused by both Mycobacterium tuberculosis and SARS-CoV-2 infection. Currently, the prevalence status, treatment and outcomes of the coinfection are poorly characterised. We aimed to systematically review the evidence on this topic and provide comprehensive information to guide the control and treatment of TB-COVID coinfection. METHODS: An extensive screening was conducted using six electronic databases to search eligible studies from 1 November 2019 to 19 March 2021. Prevalence rate, treatment and outcomes of TB-COVID coinfection were extracted. Random-effects models were used to calculate mean fatality rates of coinfection with 95% CIs. The risks of bias were assessed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Study Reporting Prevalence Data and JBI Critical Appraisal Checklist for Case Report. A meta-analysis was conducted for subgroups on in-hospital fatality rate. RESULTS: Forty-two studies were included into the analysis (35 case reports and 7 retrospective cohort studies). Nineteen countries reported coinfected patients, including high and low TB prevalence countries. The only study revealing prevalence rate came from West Cape Province, South Africa (people aged above 20 years, 0.04% until 1 June 2020 and 0.06% until 9 June 2020). The treatment regimens for coinfected patients were highly heterogeneous. The mean overall and in-hospital fatality rates of coinfection were 13.9% (95% CI: 1.6% to 26.2%) and 17.5% (95% CI: 8.9% to 26.0%). The mean in-hospital fatality rates for high-income countries (Italy and Argentina) and low/middle-income countries (LMICs) (India, Philippines, South Africa) were 6.5% (95% CI: -0.8% to ~13.9%) and 22.5% (95% CI: 19.0% to ~26.0%). CONCLUSION: TB-COVID coinfection is common globally, and the coinfected patients suffer from higher fatality risk than patients with normal COVID-19. Outcomes shared significant differences between high-income countries and LMICs. PROSPERO REGISTRATION NUMBER: CRD42021253660.


Subject(s)
COVID-19 , Coinfection , HIV Infections , Tuberculosis , Aged , COVID-19/epidemiology , Coinfection/epidemiology , HIV Infections/epidemiology , Humans , Prevalence , Retrospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome , Tuberculosis/epidemiology
7.
Biol Direct ; 17(1): 14, 2022 06 05.
Article in English | MEDLINE | ID: covidwho-1879251

ABSTRACT

BACKGROUND: Rodents, such as mice, are vulnerable targets, and potential intermediate hosts, of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, and Omicron. N501Y in the receptor-binding domain (RBD) of Spike protein is the key mutation dictating the mouse infectivity, on which the neighboring mutations within RBD have profound impacts. However, the impacts of mutations outside RBD on N501Y-mediated mouse infectivity remain to be explored. RESULTS: Herein, we report that two non-RBD mutations derived from mouse-adapted strain, Ins215KLRS in the N-terminal domain (NTD) and H655Y in the subdomain linking S1 to S2, enhance mouse infectivity in the presence of N501Y mutation, either alone or together. This is associated with increased interaction of Spike with mouse ACE2 and mutations-induced local conformation changes in Spike protein. Mechanistically, the H655Y mutation disrupts interaction with N657, resulting in a less tight loop that wraps the furin-cleavage finger; and the insertion of 215KLRS in NTD increases its intramolecular interaction with a peptide chain that interfaced with the RBD-proximal region of the neighboring protomer, leading to a more flexible RBD that facilitates receptor binding. Moreover, the Omicron Spike that contains Ins214EPE and H655Y mutations confer mouse infectivity > 50 times over the N501Y mutant, which could be effectively suppressed by mutating them back to wild type. CONCLUSIONS: Collectively, our study sheds light on the cooperation between distant Spike mutations in promoting virus infectivity, which may undermine the high infectiousness of Omicron variants towards mice.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Animals , Mice , Mutation , Protein Binding , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry
8.
Front Public Health ; 9: 730555, 2021.
Article in English | MEDLINE | ID: covidwho-1775859

ABSTRACT

Background: Organized sport participation (OSP) is considered as one method with the potential to increase overall physical activity (PA) levels in young people. It is essential to understand the correlates of OSP to inform future PA interventions. Purpose: This study aimed to explore the sociodemographic correlates of OSP among middle school students from the Nanjing City of China. Methods: A total of 7,097 adolescents (50.1% girls) aged 12-15 years from Nanjing, China, were recruited in this survey. Self-reported data on sex, grade, race, residence areas, proficient sport skills, and parental highest education were obtained. OSP was assessed by the question asked in the questionnaire on whether participants were involved in any "sports club or team" with the binary answer options of "yes" and "no," for statistical analysis purposes. Generalized linear models were used to determine the correlates of OSP. Results: Only 16.6% reported participating in any organized sport over the past whole year, while boys (OR = 1.34, 95% CI: 1.18-1.53) and 7th graders (OR = 1.40, 95% CI: 1.18-1.65) were more likely to participate in organized sport. Adolescents being Han ethnicity were less likely to either participate in organized sport (OR = 0.60, 95% CI: 0.40-0.92), or masterless (one or two) proficient sport skills [OR (one) = 0.27, 95%CI: 0.20-0.37; OR (two) = 0.43, 95% CI: 0.36-0.50]. Besides, both residence area and parental highest education were not significantly associated with OSP among the participating adolescents. Conclusion: The current study confirmed that only one-sixth of adolescents participate in the organized sport over the past year. At-risk population subgroups include girls, older adolescents, being Han ethnicity, and those proficient in fewer sport skills. Sex, grades, race, and proficient sport skills were significant correlates of OSP. School, community, and families need to provide more resources and support for disadvantaged populations in OSP.


Subject(s)
Sports , Students , Adolescent , Child , Exercise , Female , Humans , Male , Schools
9.
Mil Med Res ; 8(1): 68, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1639349
11.
Vaccines (Basel) ; 9(10)2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1444339

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8+ T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population. METHODS: We selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8+ T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8+ T cell-specific response was monitored. The conserved peptide-specific CD8+ T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort. RESULTS: For each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8+ T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population. CONCLUSIONS: This study provides evidence of broad-spectrum SARS-CoV-2 specific CD8+ TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19.

12.
Front Psychiatry ; 12: 647483, 2021.
Article in English | MEDLINE | ID: covidwho-1348562

ABSTRACT

Infertility usually causes mental health problems for patients and unfavorable emotions such as anxiety and depression can have an adverse effect on women's normal pregnancy. We aimed to compare the anxiety level between infertile female patients in quarantined and non-quarantined areas during the second wave of COVID-19 epidemic. A total of 759 infertile women were included in this cross-sectional study conducted through an online survey. Anxiety was measured by the State-Trait Anxiety Inventory (STAI) tool. Participants were divided into the quarantined group (QG) and non-quarantined group (Non-QG). Independent sample T-test and chi-square test were performed to examine the difference between the two groups. There was no significant difference in the average STAI score of the two groups of infertile women, but responses to the emotional state showed that women in the QG had a higher tendency to be anxious. Participants in QG spent more time paying attention to the dynamics of the epidemic every day, and their sleep (p < 0.01) and mood conditions were worse (p < 0.01) than in the Non-QG. The family relationship of QG is more tense than non-QG. Through the research on the infertility treatment information of the overall research population, it is found the average STAI-State (STAI-S) (p = 0.031) score and STAI-Trait (STAI-T) (p = 0.005) score of women who were infertile for more than 3 years were significantly higher than those of women with <2 years. The STAI-T score of infertile women who underwent in vitro fertilization (IVF) was higher than that of non-IVF women (p = 0.007), but no significant difference was observed with the STAI-S score. To conclude, although the second wave of quarantine during COVID-19 epidemic did not significantly increase anxiety in infertile women, it did lead to an increase in other negative emotions and worse family relationships. Patients with long-term infertility treatment and those who have had IVF are more anxious subgroups.

13.
Curr Opin Pharmacol ; 60: 200-207, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347566

ABSTRACT

Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated. Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and bacteria, immunoregulation, and protection of the liver, nervous system, and heart, with a focus on the potential efficacy of LJF on coronavirus disease-2019 based on network pharmacology so as to fully underpin the utilization of LJF as a medicinal herb and a favorable nutraceutical in daily life.


Subject(s)
COVID-19 Drug Treatment , Drugs, Chinese Herbal/pharmacology , Plant Extracts/pharmacology , Humans , Lonicera , Phytochemicals/pharmacology , SARS-CoV-2/drug effects
14.
Cell Death Dis ; 12(8): 762, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1338531

ABSTRACT

While vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.


Subject(s)
COVID-19 Vaccines/adverse effects , Thrombocytopenia/complications , Thromboembolism/etiology , Bone Marrow/pathology , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Fatal Outcome , Female , Humans , Lung/pathology , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/pathology , SARS-CoV-2/immunology , Thrombocytopenia/diagnosis , Thrombocytopenia/pathology
16.
J Mol Cell Biol ; 13(10): 712-720, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1319185

ABSTRACT

The coronavirus diseases 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 has caused more than 140 million infections worldwide by the end of April 2021. As an enveloped single-stranded positive-sense RNA virus, SARS-CoV-2 underwent constant evolution that produced novel variants carrying mutation conferring fitness advantages. The current prevalent D614G variant, with glycine substituted for aspartic acid at position 614 in the spike glycoprotein, is one of such variants that became the main circulating strain worldwide in a short period of time. Over the past year, intensive studies from all over the world had defined the epidemiological characteristics of this highly contagious variant and revealed the underlying mechanisms. This review aims at presenting an overall picture of the impacts of D614G mutation on virus transmission, elucidating the underlying mechanisms of D614G in virus pathogenicity, and providing insights into the development of effective therapeutics.


Subject(s)
COVID-19/transmission , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Substitution , Aspartic Acid/genetics , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Glycine/genetics , Humans , Molecular Epidemiology , Mutation , SARS-CoV-2/genetics , Severity of Illness Index , Time Factors
17.
Cell Death Differ ; 28(9): 2765-2777, 2021 09.
Article in English | MEDLINE | ID: covidwho-1195611

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.


Subject(s)
COVID-19/virology , Giant Cells/virology , Lymphocytes/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/pathology , Cell Line , Cell Line, Tumor , Giant Cells/pathology , HEK293 Cells , HeLa Cells , Humans , Jurkat Cells , K562 Cells , Lymphocytes/pathology , Virus Internalization , Virus Replication/genetics
18.
Front Pharmacol ; 11: 1071, 2020.
Article in English | MEDLINE | ID: covidwho-726004

ABSTRACT

BACKGROUND: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, causing an unprecedented pandemic. However, there is no specific antiviral therapy for coronavirus disease 2019 (COVID-19). We conducted a clinical trial to compare the effectiveness of three antiviral treatment regimens in patients with mild to moderate COVID-19. METHODS: This was a single-center, randomized, open-labeled, prospective clinical trial. Eligible patients with mild to moderate COVID-19 were randomized into three groups: ribavirin (RBV) plus interferon-α (IFN-α), lopinavir/ritonavir (LPV/r) plus IFN-α, and RBV plus LPV/r plus IFN-α at a 1:1:1 ratio. Each patient was invited to participate in a 28-d follow-up after initiation of an antiviral regimen. The outcomes include the difference in median interval to SARS-CoV-2 nucleic acid negativity, the proportion of patients with SARS-CoV-2 nucleic acid negativity at day 14, the mortality at day 28, the proportion of patients re-classified as severe cases, and adverse events during the study period. RESULTS: In total, we enrolled 101 patients in this study. Baseline clinical and laboratory characteristics of patients were comparable among the three groups. In the analysis of intention-to-treat data, the median interval from baseline to SARS-CoV-2 nucleic acid negativity was 12 d in the LPV/r+IFN-α-treated group, as compared with 13 and 15 d in the RBV+IFN-α-treated group and in the RBV+LPV/r+ IFN-α-treated group, respectively (p=0.23). The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-α-treated group (61.1%) was higher than the RBV+ IFN-α-treated group (51.5%) and the RBV+LPV/r+IFN-α-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The RBV+LPV/r+IFN-α-treated group developed a significantly higher incidence of gastrointestinal adverse events than the LPV/r+ IFN-α-treated group and the RBV+ IFN-α-treated group. CONCLUSIONS: Our results indicate that there are no significant differences among the three regimens in terms of antiviral effectiveness in patients with mild to moderate COVID-19. Furthermore, the combination of RBV and LPV/r is associated with a significant increase in gastrointestinal adverse events, suggesting that RBV and LPV/r should not be co-administered to COVID-19 patients simultaneously. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, ID: ChiCTR2000029387. Registered on January 28, 2019.

19.
JMIR Public Health Surveill ; 6(4): e24291, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-976125

ABSTRACT

BACKGROUND: Since the outbreak of COVID-19 in December 2019 in Wuhan, Hubei Province, China, frequent interregional contacts and the high rate of infection spread have catalyzed the formation of an epidemic network. OBJECTIVE: The aim of this study was to identify influential nodes and highlight the hidden structural properties of the COVID-19 epidemic network, which we believe is central to prevention and control of the epidemic. METHODS: We first constructed a network of the COVID-19 epidemic among 31 provinces in mainland China; after some basic characteristics were revealed by the degree distribution, the k-core decomposition method was employed to provide static and dynamic evidence to determine the influential nodes and hierarchical structure. We then exhibited the influence power of the above nodes and the evolution of this power. RESULTS: Only a small fraction of the provinces studied showed relatively strong outward or inward epidemic transmission effects. The three provinces of Hubei, Beijing, and Guangzhou showed the highest out-degrees, and the three highest in-degrees were observed for the provinces of Beijing, Henan, and Liaoning. In terms of the hierarchical structure of the COVID-19 epidemic network over the whole period, more than half of the 31 provinces were located in the innermost core. Considering the correlation of the characteristics and coreness of each province, we identified some significant negative and positive factors. Specific to the dynamic transmission process of the COVID-19 epidemic, three provinces of Anhui, Beijing, and Guangdong always showed the highest coreness from the third to the sixth week; meanwhile, Hubei Province maintained the highest coreness until the fifth week and then suddenly dropped to the lowest in the sixth week. We also found that the out-strengths of the innermost nodes were greater than their in-strengths before January 27, 2020, at which point a reversal occurred. CONCLUSIONS: Increasing our understanding of how epidemic networks form and function may help reduce the damaging effects of COVID-19 in China as well as in other countries and territories worldwide.


Subject(s)
COVID-19/epidemiology , Models, Statistical , COVID-19/transmission , China/epidemiology , Disease Outbreaks/statistics & numerical data , Humans , Pandemics , Time
20.
Biochem Soc Trans ; 48(5): 2307-2316, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-975033

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by a novel virus of the ß-coronavirus genus (SARS-CoV-2), has been spreading globally. As of July 2020, there have been more than 17 million cases worldwide. Determining multiple transmission routes of SARS-CoV-2 is critical to improving safety practices for the public and stemming the spread of SARS-CoV-2 effectively. This article mainly focuses on published studies on the transmission routes of SARS-CoV-2 including contact transmission, droplet transmission, aerosol transmission and fecal-oral transmission, as well as related research approaches, such as epidemiological investigations, environmental sampling in hospitals and laboratories and animal models. We also provide four specific recommendations for the prevention and control of SARS-CoV-2 that may help reduce the risk of SARS-CoV-2 infection under different environmental conditions. First, social distancing, rational use of face masks and respirators, eye protection, and hand disinfection for medical staff and the general public deserve further attention and promotion. Second, aerodynamic characteristics, such as size distribution, release regularity, aerosol diffusion, survival and decline, infectious dose and spread distance, still require further investigation in order to identify the transmissibility of COVID-19. Third, background monitoring of the distribution of pathogenic microorganisms and environmental disinfection in crowded public places, such as railway stations, schools, hospitals and other densely populated areas, can give early warning of outbreaks and curb the transmission routes of SARS-CoV-2 in those high-risk areas. Forth, establishing novel predictive models can help us to not only assess transmission and impacts in communities, but also better implement corresponding emergency response measures.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Animals , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Models, Animal , Humans , Infection Control/methods , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Polymerase Chain Reaction , SARS-CoV-2
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