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1.
Cell Mol Immunol ; 19(5): 577-587, 2022 May.
Article in English | MEDLINE | ID: covidwho-1830043

ABSTRACT

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Histones , Mice , N-Acetylneuraminic Acid , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization
2.
Front Public Health ; 10: 726924, 2022.
Article in English | MEDLINE | ID: covidwho-1775963

ABSTRACT

Background: Taiwan faced a surge of COVID-19 infections in May 2021. Because new cases were quickly increasing, parents called for school closures. A national parent group used an online survey to collect opinions about upcoming school closings planned by the Ministry of Education. This study evaluated the results of the survey for all respondents and investigated the level of viral transmission following school closures among students in Taiwan. Methods: An online survey titled "Survey of Opinions of School Closures during the Current COVID-19 Outbreak" (SOSC-COVID-19) was designed by the national parent association and then distributed to members of the community throughout Taiwan via local parent groups from May 17 to 18, 2021. The survey included an open-ended respondents' opinions about school closures. Differences among regions and socioeconomic scores (SES) were analyzed with chi-square tests. Results: A total of 8,703 completed survey forms data were analyzed. Nearly all respondents (7,973, 91.6%) approved of school closures; there were no differences of opinions inside and outside municipalities or by regional SES scores. Only 8.4% of respondents were opposed to any type of school closure, believing parents should decide whether their child attended school, which also did not vary with region or SES score. Qualitative feedback from parent and teacher responders indicated students' health and economic impacts were additional concerns that influenced their choice of whether the government or parents should decide about school closures. On the afternoon of May 18, 2021, the government of Taiwan closed all schools. Although a spike in new cases of COVID-19 occurred among students 10 days after school closures, over the next 40 days new cases declined, falling to zero by July 5th. Conclusions: Despite the inability of nationwide school closures to completely halt transmission of the virus within families during the COVID-19 outbreak, school closures helped to impede transmission between students.


Subject(s)
COVID-19 , COVID-19/epidemiology , Child , Disease Outbreaks , Humans , Schools , Surveys and Questionnaires , Taiwan/epidemiology
3.
Front Nutr ; 9: 786972, 2022.
Article in English | MEDLINE | ID: covidwho-1775724

ABSTRACT

Communicable diseases are illnesses caused by pathogenic biological agents, including viruses, bacteria, fungi, parasites, and protozoa. Such diseases spread among people through contact with contaminated surfaces, bodily fluids, or blood products, or through the air, insect bites, or consuming contaminated food and beverages. Although some communicable diseases can be treated or prevented by taking medication and vaccines, there has been an increase in awareness of adopting a healthy diet to aid in the prevention and reversal of these diseases. One popular diet is a plant-based diet. Plant-based diets generally consist of vegetables, grains, nuts, seeds, legumes, and fruits, without any animal-source foods or artificial ingredients. Over the years, this diet has continuously increased in popularity. Reasons for following a plant-based diet are varied but include health benefits, such as improving immunity, and reducing the risk of heart disease, diabetes, and some cancers. Scientific evidence even shows that just an increased vegetable intake can decrease the occurrence of chronic diseases caused by viruses, such as hepatitis viruses, and reduce the risk of severe coronavirus disease 2019. Therefore, this mini review discusses the effectiveness of adopting a plant-based diet in ameliorating diseases caused by selected viruses and its limitations.

4.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1696733

ABSTRACT

JAK1 depletion or downregulation was previously reported to account for coronavirus inhibition. Here, we found that AG1024, an IR (insulin receptor) and IGF-1R (insulin-like growth factor 1 receptor) inhibitor, diminishes JAK1 protein levels and exerts anti-coronaviral activities with EC50 values of 5.2 ± 0.3 µM against transmissible gastroenteritis coronavirus (TGEV) and 4.3 ± 0.3 µM against human flu coronavirus OC43. However, although the IR and IGF-1R signaling pathways are activated by insulin or IGF-1 in swine testis cells, they are not triggered upon TGEV infection. AG1024, therefore, inhibits coronaviral replication and downregulates JAK1 protein levels independently of IR and IGF-1R. Moreover, JAK1 proteolysis caused by AG1024 was found through activation of upstream Ndfip1/2 and its effector NEDD4-like E3 ligase Itch. In addition, ouabain, which was reported to mediate JAK1 proteolysis causing anti-coronaviral activity by activation of Ndfip1/2 and NEDD4 E3 ligase, additively inhibited anti-coronaviral activity and JAK1 diminishment in combination with AG1024. This study provides novel insights into the pharmacological effects of AG1024 and Itch E3 ligase mediated JAK1 proteolysis and identified Ndfip1/2 as a cognate effector for JAK1 proteolysis via the diversified E3 ligases NEDD4 and NEDD4-like Itch. These findings are expected to provide valued information for the future development of anti-viral agents.

5.
Clin Med Insights Arthritis Musculoskelet Disord ; 15: 11795441221081061, 2022.
Article in English | MEDLINE | ID: covidwho-1759636

ABSTRACT

Under the ongoing COVID-19 pandemic, vaccines have become the crucial players to reduce the spread of the infection. Among them, the ChAdOx1 nCoV-19 vaccine is an adenoviral vector vaccine with an overall efficacy of 70.4% in protection. The engineered adenovirus contains the SARS-CoV-2 spike protein gene and pushes its DNA into the vaccinated cell's nucleus and subsequently, the spike protein can be made. During vaccination, the genome transition of adenovirus is influenced by the architecture and dynamics of the microtubule. Colchicine can alter microtubule dynamics by suppressing microtubule dynamics at lower concentrations and inducing depolymerization of microtubules at higher concentrations. Accordingly, the delivery of the genome to the vaccinated cell's nucleus by the adenoviral vector could be hindered under the presence of colchicine. Nevertheless, colchicine is a common medication for gout therapy worldwide, and though not recommended by guidelines, colchicine has even been taken into consideration as a possible therapeutic option for COVID-19 infection. Given the above reasons and the worldwide use of colchicine, the impact of colchicine on the efficacy of the COVID-19 vaccine via adenoviral vector should be viewed cautiously.

6.
Nat Commun ; 13(1): 1444, 2022 03 17.
Article in English | MEDLINE | ID: covidwho-1751716

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.


Subject(s)
COVID-19 , Virus Internalization , Animals , Humans , Mice , RNA , SARS-CoV-2 , Serine Endopeptidases/genetics
7.
JAMA Netw Open ; 5(3): e221455, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1729077

ABSTRACT

Importance: Current guidelines recommend use of dexamethasone, 6 mg/d, up to 10 days or until discharge for patients hospitalized with COVID-19. Whether patients who received less than 10 days of corticosteroids during hospitalization for COVID-19 benefit from continuing treatment at discharge has not been determined. Objective: To assess whether continuing dexamethasone treatment at discharge is associated with reduced all-cause readmissions or mortality postdischarge. Design, Setting, and Participants: A retrospective cohort study was conducted at 15 medical centers within Kaiser Permanente Southern California. The population included adults who received less than 10 days of dexamethasone, 6 mg/d, until discharge during hospitalization for COVID-19 and were discharged alive between May 1 and September 30, 2020. Exposures: Continued dexamethasone treatment at discharge. Main Outcomes and Measures: All-cause readmissions or mortality within 14 days from discharge. Results: A total of 1164 patients with a median age of 55 (IQR, 44-66) years were identified. Most patients were of Hispanic ethnicity (822 [70.6%]) and male (674 [57.9%]) and required oxygen support during hospitalization (1048 [90.0%]). Of the 1164 patients, 692 (59.5%) continued dexamethasone, 6 mg/d, at discharge. A balanced cohort was created using propensity score and inverse probability of treatment weighting. The adjusted odds ratio (OR) for readmissions or mortality within 14 days was 0.87 (95% CI, 0.58-1.30) for patients who continued dexamethasone therapy at discharge compared with those who did not. Similar results were produced by a sensitivity analysis that restricted the treatment group to those who received exactly 10 days of dexamethasone (OR, 0.89; 95% CI, 0.55-1.43) and by subgroup analyses stratified by the duration of dexamethasone treatment as an inpatient (1-3 days: OR, 0.71; 95% CI, 0.43-1.16; 4-9 days: OR, 1.01; 95% CI, 0.48-2.12), oxygen requirement at discharge (room air: OR, 0.91; 95% CI, 0.53-1.59; supplemental oxygen use: OR, 0.76; 95% CI, 0.42-1.37), and disease duration at discharge (≤10 days: OR, 0.81; 95% CI, 0.49-1.33; >10 days: OR, 0.94; 95% CI, 0.48-1.86). Conclusions and Relevance: In this cohort study of patients with COVID-19, continuing treatment with dexamethasone, 6 mg/d, at discharge was not associated with a reduction in 14-day all-cause readmission or mortality. This finding suggests that dexamethasone should not be routinely prescribed beyond discharge for individuals with COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Patient Discharge , Patient Readmission , Practice Patterns, Physicians' , SARS-CoV-2 , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , COVID-19/mortality , California , Cohort Studies , Dexamethasone/administration & dosage , Female , Humans , Male , Middle Aged , Retrospective Studies
8.
Sci Transl Med ; 14(639): eabm0899, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1714341

ABSTRACT

A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (SMG) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from SMG-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.


Subject(s)
COVID-19 Vaccines , Polysaccharides , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/metabolism , Humans , Mice , Models, Animal , SARS-CoV-2 , Vaccination
10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325122

ABSTRACT

Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (COVID-19) emerged in Wuhan, China. The number of cases has increased rapidly, severe patients have a poor prognosis and there are no effective therapies or vaccines for it. Only one rapid advice guideline for symptomatic supportive care has been used for it. A Traditional Chinese medicine Rehabilitation(TCMR) program consisting of acupressure therapy and Liuzijue Qigong can be used as a complementary therapy for COVID-19.Hence, we designed a randomized trial to evaluate the efficacy and advantages of TCMR for treating severe patients with COVID-19. Methods: /design : This is a parallel-design, two-arm, analyst-assessor blinded, randomized controlled trial. A total of 120 patients with COVID-19 aged from 20 to 80 will be recruited and assigned randomly into a guideline therapy group and a guideline therapy plus TCMR group at a 1:1 ratio. Patients in both groups will receive guideline therapy. The patients in intervention group will perform acupressure therapy and Liuzijue Qigong exercise on the basis of conventional treatments, twice a day, and have been persistent from admission to discharge. The primary outcomes are measured with Modified Dyspnea Scale (MDS) and Activities of Daily Living (ADL). The secondary outcomes include Patient Health Questionnaire-9 (PHQ-9), Length of Hospital Stay (LHS), Respiratory Symptoms (RS), Liver function test, Renal function test and lung CT. Clinical assessments will at three points (before treatment, 7th day during hospitalization and the discharge day). Adverse events will be noted and recorded for the safety evaluation. Discussion: This trail will provide a high-quality evidence of the value of TCMR, which is consist of acupressure therapy and Liuzijue Qigong exercise for treating severe patients with COVID-19.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029994 Registered 18 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=49309

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319503

ABSTRACT

This study aimed to analyze aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in COVID-19 patients. After exclusion, 567 inpatients were included in this study and separated into two groups according to their AST/ALT ratio on admission. Poor prognosis included death and transfer to other hospitals due to deterioration. Of 567 patients, 56 (9.9%) had AST/ALT ≥ 2. Of the 56 patients, older age (median age 65.5 years), fatigue (29 [51.8%] cases), comorbidities (33 [58.9%] cases) and outcomes were significantly different from patients with AST/ALT < 2. They also had worse chest computed tomography (CT) findings, laboratory results and severity scores. Levels of platelet count (OR = 0.989, 95% CI [0.983-0.996]) were independently associated with AST/ALT ≥ 2 on admission. Furthermore, a high AST/ALT ratio on admission was an independent risk factor for poor prognosis (OR = 22.02, 95% CI [1.84-263.2]), especially in patients with AST levels > 40 U/L. In subsequent monitoring, the AST/ALT ratio was decreased in both patients with AST/ALT < 2 or ≥ 2 on admission. COVID-19 patients who are older, or have fatigue, comorbidities are more likely to have AST/ALT ≥ 2 on admission, which might be the indication of worse status and outcomes.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317668

ABSTRACT

Social media is an appropriate source for analyzing public attitudes towards the COVID-19 vaccine and various brands. Nevertheless, there are few relevant studies. In the research, we collected tweet posts by the UK and US residents from the Twitter API during the pandemic and designed experiments to answer three main questions concerning vaccination. To get the dominant sentiment of the civics, we performed sentiment analysis by VADER and proposed a new method that can count the individual's influence. This allows us to go a step further in sentiment analysis and explain some of the fluctuations in the data changing. The results indicated that celebrities could lead the opinion shift on social media in vaccination progress. Moreover, at the peak, nearly 40\% of the population in both countries have a negative attitude towards COVID-19 vaccines. Besides, we investigated how people's opinions toward different vaccine brands are. We found that the Pfizer vaccine enjoys the most popular among people. By applying the sentiment analysis tool, we discovered most people hold positive views toward the COVID-19 vaccine manufactured by most brands. In the end, we carried out topic modelling by using the LDA model. We found residents in the two countries are willing to share their views and feelings concerning the vaccine. Several death cases have occurred after vaccination. Due to these negative events, US residents are more worried about the side effects and safety of the vaccine.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310222

ABSTRACT

Abstract BackgroundSince its outbreak, COVID-19 has continued to spread rapidly more than 3 months, which constituted a public health emergence worldwide.The onset symptoms of patients with COVID-19 are not specific, especially in non-respiratory symptoms, it is easy to be ignored, which can cause widespread infection. For critically ill patients, glucocorticoids are used for anti-inflammatory treatment. However, after the application cycle recommended by the guidelines, the deterioration of the patient's condition and treatment to suppress cytokine storms is more critical.Case presentationA previous patient was admitted to the hospital due to abdominal pain and diarrhea, and accidentally was confirmed with positive SARS-CoV-2. The patient progressed rapidly from mild to severe within 2 days of admission. With timely anti-viral and anti-inflammatory drugs and early ventilator respiratory support, the patient's condition improved temporarily, and subsequently accompanied by a decrease in glucocorticoids, the patient's condition worsened and eventually died. Her family members were also hospitalized due to close contact.ConclusionThis case highlights that even if glucocorticoids are discontinued in accordance with the guidelines, deterioration of the patient's condition is inevitable attribute to the cytokine storms. And related Chinese and western medicines that suppress cytokine storms should be applied in time. In addition, more systematic epidemiological surveillance and stool tests are necessary due to potential lethal risk and route of transmission.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308259

ABSTRACT

Background: . SARS-COV-2 causes digestive system symptom, the effect of which remains equivocal. Methods: . Patients with COVID-19 were classified into 4 groups according to symptom. The study traced the onset and duration of symptoms, compared laboratory examinations and conducted bioinformatic analysis. Immune indices were further analyzed. Results: . By March 16, 25 patients with COVID-19 and 13 with suspect COVID-19 were admitted to West China Hospital, Sichuan University. Digestive system symptom group had the highest level of ESR (mm/h, P <0.0001), serum ferritin (ng/ml, P <0.0001), hepatic enzymes ( P <0.05), and retentive lymphocyte count/percentage ( P <0.05) and its subsets ( P <0.05). Combined group (respiratory combined with subsequent digestive system symptom) had the highest level of IL-6 (pg/ml, P =0.0046), CRP (mg/L, P =0.0004) and moderate lymphocyte depletion. Respiratory system symptom and asymptomatic groups suffered the most from lymphocyte depletion ( P <0.05). Bioinformatic analysis indicated co-expression of binding related proteins of SARS-COV-2 (ACE2, TMPRSS2 and Furin) in small intestine. CD147 was extensively expressed in alimentary tract. CTSL, PIKfyve, TPC2 and CTSB could be detected with ≥moderate expressions in a variety of organs including alimentary system. Conclusions: . Alimentary system is directly attacked by SARS-COV-2 other than hyperinflammation and immune dysregulation. Involvement of alimentary system might further protect mild and moderate cases from lymphocyte depletion caused by COVID-19.

15.
Cereb Cortex ; 2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1684532

ABSTRACT

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anticorrelated genetic constructs. The Mendelian randomization approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people's lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, body mass index (BMI), and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.

16.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Article in English | MEDLINE | ID: covidwho-1684242

ABSTRACT

Development of the messenger RNA (mRNA) vaccine has emerged as an effective and speedy strategy to control the spread of new pathogens. After vaccination, the mRNA is translated into the real protein vaccine, and there is no need to manufacture the protein in vitro. However, the fate of mRNA and its posttranslational modification inside the cell may affect immune response. Here, we showed that the mRNA vaccine of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with deletion of glycosites in the receptor-binding domain (RBD) or especially the subunit 2 (S2) domain to expose more conserved epitopes elicited stronger antibody and CD8+ T cell responses with broader protection against the alpha, beta, gamma, delta, and omicron variants, compared to the unmodified mRNA. Immunization of such mRNA resulted in accumulation of misfolded spike protein in the endoplasmic reticulum, causing the up-regulation of BiP/GRP78, XBP1, and p-eIF2α to induce cell apoptosis and strong CD8+ T cell response. In addition, dendritic cells (DCs) incubated with S2-glysosite deleted mRNA vaccine increased class I major histocompatibility complex (MHC I) expression. This study provides a direction for the development of broad-spectrum mRNA vaccines which may not be achieved with the use of expressed proteins as antigens.


Subject(s)
COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Viral/immunology , Antibody Formation , CD8-Positive T-Lymphocytes/immunology , Cytokines/metabolism , Glycosylation , HEK293 Cells , Histocompatibility Antigens/metabolism , Humans , Immunity , Mice, Inbred BALB C , Unfolded Protein Response , Vaccines, Synthetic/immunology , /immunology
17.
Signal Transduct Target Ther ; 7(1): 26, 2022 01 27.
Article in English | MEDLINE | ID: covidwho-1655545

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Design/trends , Drug Repositioning , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/chemistry , Adrenal Cortex Hormones/therapeutic use , Antibodies, Viral/chemistry , Antibodies, Viral/therapeutic use , Antiviral Agents/chemistry , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/therapeutic use , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Humans , Models, Molecular , Nucleosides/chemistry , Nucleosides/therapeutic use , Protein Conformation , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , Virus Internalization/drug effects , Virus Release/drug effects , Virus Replication/drug effects
18.
JAMA Netw Open ; 5(1): e2143160, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1640613

ABSTRACT

Importance: Physicians self-report high levels of symptoms of anxiety and depression, and surveys suggest these symptoms have been exacerbated by the COVID-19 pandemic. However, it is not known whether pandemic-related stressors have led to increases in health care visits related to mental health or substance use among physicians. Objective: To evaluate the association between the COVID-19 pandemic and changes in outpatient health care visits by physicians related to mental health and substance use and explore differences across physician subgroups of interest. Design, Setting, and Participants: A population-based cohort study was conducted using health administrative data collected from the universal health system (Ontario Health Insurance Plan) of Ontario, Canada, from March 1, 2017, to March 10, 2021. Participants included 34 055 physicians, residents, and fellows who registered with the College of Physicians and Surgeons of Ontario between 1990 and 2018 and were eligible for the Ontario Health Insurance Plan during the study period. Autoregressive integrated moving average models and generalized estimating equations were used in analyses. Exposures: The period during the COVID-19 pandemic (March 11, 2020, to March 10, 2021) compared with the period before the pandemic. Main Outcomes and Measures: The primary outcome was in-person, telemedicine, and virtual care outpatient visits to a psychiatrist or family medicine and general practice clinicians related to mental health and substance use. Results: In the 34 055 practicing physicians (mean [SD] age, 41.7 [10.0] years, 17 918 [52.6%] male), the annual crude number of visits per 1000 physicians increased by 27%, from 816.8 before the COVID-19 pandemic to 1037.5 during the pandemic (adjusted incident rate ratio per physician, 1.13; 95% CI, 1.07-1.19). The absolute proportion of physicians with 1 or more mental health and substance use visits within a year increased from 12.3% before to 13.4% during the pandemic (adjusted odds ratio, 1.08; 95% CI, 1.03-1.14). The relative increase was significantly greater in physicians without a prior mental health and substance use history (adjusted incident rate ratio, 1.72; 95% CI, 1.60-1.85) than in physicians with a prior mental health and substance use history. Conclusions and Relevance: In this study, the COVID-19 pandemic was associated with a substantial increase in mental health and substance use visits among physicians. Physician mental health may have worsened during the pandemic, highlighting a potential greater requirement for access to mental health services and system level change.


Subject(s)
COVID-19 , Mental Health , Pandemics , Patient Acceptance of Health Care , Physicians/psychology , Stress, Psychological , Substance-Related Disorders , Adult , Ambulatory Care , Anxiety , Cohort Studies , Depression , Family Practice , Female , Humans , Male , Mental Disorders , Middle Aged , Ontario , Psychiatry , Psychological Distress , SARS-CoV-2 , Telemedicine
19.
Arch Virol ; 167(2): 577-581, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1639483

ABSTRACT

Outbreaks of acute hemorrhagic conjunctivitis (AHC) are associated with a high disease burden. In this study, we investigated the association between enhanced public health intervention and the incidence of AHC during the COVID-19 pandemic in China. A total of 212,526 AHC cases were reported in China during 2015-2020. The overall yearly incidence rate and number of AHC cases decreased by 23.08% and 22.15%, respectively, during the COVID-19 epidemic, compared with the previous 5 years (all p < 0.001). Significant reductions in AHC incidence were found both during the emergency period and after the relaxation of emergency measures in 2020 compared to the previous 5 years (22.22% and 28.00% reduction, respectively; p < 0.001). Enhanced public health initiatives during the COVID-19 pandemic in China were therefore associated with lower transmission of pathogens causing AHC.


Subject(s)
COVID-19 , Conjunctivitis, Acute Hemorrhagic , China/epidemiology , Conjunctivitis, Acute Hemorrhagic/epidemiology , Conjunctivitis, Acute Hemorrhagic/prevention & control , Disease Outbreaks , Humans , Incidence , Pandemics , Public Health , SARS-CoV-2
20.
Virol J ; 18(1): 257, 2021 12 27.
Article in English | MEDLINE | ID: covidwho-1639183

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein determines virus entry and the palmitoylation of S protein affects virus infection. An acyltransferase complex ZDHHC5/GOGAL7 that interacts with S protein was detected by affinity purification mass spectrometry (AP-MS). However, the palmitoylated cysteine residues of S protein, the effects of ZDHHC5 or GOLGA7 knockout on S protein's subcellular localization, palmitoylation, pseudovirus entry and the enzyme for depalmitoylation of S protein are not clear. METHODS: The palmitoylated cysteine residues of S protein were identified by acyl-biotin exchange (ABE) assays. The interactions between S protein and host proteins were analyzed by co-immunoprecipitation (co-IP) assays. Subcellular localizations of S protein and host proteins were analyzed by fluorescence microscopy. ZDHHC5 or GOGAL7 gene was edited by CRISPR-Cas9. The entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells were analyzed by measuring the activity of Renilla luciferase. RESULTS: In this investigation, all ten cysteine residues in the endodomain of S protein were palmitoylated. The interaction of S protein with ZDHHC5 or GOLGA7 was confirmed. The interaction and colocalization of S protein with ZDHHC5 or GOLGA7 were independent of the ten cysteine residues in the endodomain of S protein. The interaction between S protein and ZDHHC5 was independent of the enzymatic activity and the PDZ-binding domain of ZDHHC5. Three cell lines HEK293T, A549 and Hela lacking ZDHHC5 or GOLGA7 were constructed. Furthermore, S proteins still interacted with one host protein in HEK293T cells lacking the other. ZDHHC5 or GOLGA7 knockout had no significant effect on S protein's subcellular localization or palmitoylation, but significantly decreased the entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells, while varying degrees of entry efficiencies may be linked to the cell types. Additionally, the S protein interacted with the depalmitoylase APT2. CONCLUSIONS: ZDHHC5 and GOLGA7 played important roles in SARS-CoV-2 pseudovirus entry, but the reason why the two host proteins affected pseudovirus entry remains to be further explored. This study extends the knowledge about the interactions between SARS-CoV-2 S protein and host proteins and probably provides a reference for the corresponding antiviral methods.


Subject(s)
Acyltransferases , COVID-19 , Golgi Matrix Proteins/metabolism , Lipoylation , Spike Glycoprotein, Coronavirus , Cysteine , Golgi Matrix Proteins/genetics , HEK293 Cells , HeLa Cells , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
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