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2.
Front Psychiatry ; 12: 644899, 2021.
Article in English | MEDLINE | ID: covidwho-1526792

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has been a global emergency, affecting millions of individuals both physically and psychologically. The present research investigated the associations between social media exposure and depression during the COVID-19 outbreak by examining the mediating role of psychological distress and the moderating role of emotion regulation among members of the general public in China. Participants (N = 485) completed a set of questionnaires online, including demographic information, self-rated physical health, and social media exposure to topics related to COVID-19. The Impact of Event Scale-Revised (IES-R), the Beck Depression Inventory-II (BDI-II), and the Emotion Regulation Questionnaire (ERQ) were utilized to measure psychological distress about COVID-19, depression, and emotion regulation strategies, respectively. Results found that older age and greater levels of social media exposure were associated with more psychological distress about the virus (r = 0.14, p = 0.003; r = 0.22, p < 0.001). Results of the moderated mediation model suggest that psychological distress mediated the relationship between social media exposure and depression (ß = 0.10; Boot 95% CI = 0.07, 0.15). Furthermore, expressive suppression moderated the relationship between psychological distress and depression (ß = 0.10, p = 0.017). The findings are discussed in terms of the need for mental health assistance for individuals at high risk of depression, including the elderly and individuals who reported greater psychological distress and those who showed preference usage of suppression, during the COVID-19 crisis.

3.
J Clin Invest ; 131(21)2021 11 01.
Article in English | MEDLINE | ID: covidwho-1495789

ABSTRACT

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , COVID-19/virology , Killer Cells, Natural/immunology , Receptors, Natural Killer Cell/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Animals , Antigens, Differentiation, T-Lymphocyte/immunology , Cell Adhesion Molecules/immunology , Cohort Studies , Cytotoxicity, Immunologic , Female , Heterografts , Host Microbial Interactions/immunology , Humans , Immunophenotyping , In Vitro Techniques , Ligands , Male , Mice , Mice, SCID , Middle Aged , NK Cell Lectin-Like Receptor Subfamily D/immunology , Pandemics , Receptors, Immunologic/immunology , Receptors, Virus/immunology , Viral Load , Young Adult
4.
Zhongguo Weishengtaxixue Zazhi / Chinese Journal of Microecology ; 32(5):586-590, 2020.
Article in Chinese | GIM | ID: covidwho-1497981

ABSTRACT

Objective To analyze the epidemiological characteristics of coronavirus disease 2019(COVID-19) in Qingdao. Methods All the patients diagnosed as COVID-19 in Qingdao from January 21, 2020 to March 3, 2020 were included. The demographic and epidemiological data were collected. The susceptible population, transmission model, basic reproduction number(R0), progress of epidemic situation, and preventive measures were analyzed. Results A total of 60 cases of COVID-19 were enrolled, including 27 imported cases and 33 locally transmitted cases. The proportion of females in locally transmitted cases was 69.7%, which was significantly higher than that of imported cases(X2=6.400, P=0.011). Three infected generations were found in locally transmitted cases. The quantity of infected cases had a decreasing trend with generation sequentially increased. The R0 value of all cases in Qingdao was 1.49. The R0 s of first, second and third generations were 1.38, 1.53 and 1.56, respectively. The model of transmission converted from family aggregation to close contacts. Conclusion Females are susceptible to COVID-19 in Qingdao. The trend of new daily cases is wavily declining and the epidemic has been basically controlled. It is necessary to do a good job in zoning, grading and precise prevention and control, strengthen the isolation and observation of foreign population to prevent the rebound of COVID-19.

5.
Antioxidants (Basel) ; 10(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1480546

ABSTRACT

To investigate the effects of tannins (TA) on porcine oocyte in vitro maturation (IVM), different concentrations of TA (0, 1, 10 and 100 µg/mL) were supplemented with a maturation medium and the COCs and subsequent embryonic development were examined. The results showed that 10 µg/mL TA significantly improved the cumulus expansion index (CEI), cumulus-expansion-related genes (PTGS1, PTGS2, PTX-3, TNFAIP6 and HAS2) expression and blastocyst formation rates after parthenogenetic activation (PA), in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) compared to the control groups, but not oocyte nuclear maturation. Nevertheless, 10 µg/mL TA dramatically enhanced the mRNA expression of oocyte-development-related genes (BMP15, GDF9, CDC2 and CYCLIN B1), GSH, ATP, SOD1, PGC1α, BMP15, GDF9 and CDC2 levels and reduced intracellular ROS level in porcine oocytes. These results indicated that porcine oocyte cytoplasmic maturation was improved by 10 µg/mL TA treatment during IVM. In contrast, a high concentration of TA (100 µg/mL) significantly decreased the CEI and PTGS1, PTGS2, PTX-3 and HAS2 mRNA expressions in cumulus cells, and reduced oocyte nuclear maturation and the total cell numbers/blastocyst. In general, these data showed that 10 µg/mL TA supplementation has beneficial effects on oocyte cytoplasmic maturation and subsequent embryonic development in pigs.

6.
Sustainability ; 13(20):11474, 2021.
Article in English | MDPI | ID: covidwho-1470981

ABSTRACT

COVID-19 caused an unprecedented public health crisis and was declared a global pandemic on 11 March 2020, by the World Health Organization. The Taiwanese government’s early deployment mitigated the effect of the pandemic, yet the breakout in May 2021 brought a new challenge. This study focuses on examining Taiwanese newspaper articles regarding the government response before and after the soft lockdown, collecting 125,570 articles reported by three major news channels from 31 December 2019, to 30 June 2021, and splitting them into four stages. Latent Dirichlet Allocation topic modeling and sentiment analysis were used to depict the overall picture of Taiwan’s pandemic. While the news media focused on the impact and shock of the pandemic in the initial stage, prevention measures were more present in the last stage. Then, to focus on the government response indicators, we retrieved 31,089 related news from 125,570 news articles and categorized them into ten indicators, finding the news centered on the fundamental measures that were taken early and that were transformed into advanced measures in the latest and hardest period of the pandemic. Furthermore, this paper examines the temporal distribution of the news related to each indicator with the support of a sentiment analysis of the news’ titles and content, indicating the preparation of Taiwanese society to confront the pandemic.

7.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi ; 2021.
Article in English | EuropePMC | ID: covidwho-1451502

ABSTRACT

<h4>Background</h4> Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. <h4>Methods</h4> This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children’s Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. <h4>Results</h4> Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was M. pneumoniae. <h4>Conclusions</h4> FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

8.
Medicina (Kaunas) ; 57(10)2021 Sep 25.
Article in English | MEDLINE | ID: covidwho-1438664

ABSTRACT

The adverse effects of the COVID-19 vaccine have been discovered as the rapid application of the vaccines continues. Neurological complications such as transverse myelitis raise concerns as cases were observed in clinical trials. Transverse myelitis is a rare immune-mediated disease with spinal cord neural injury, resulting in neurological deficits in the motor, sensory, and autonomic system. Vaccine-related transverse myelitis is even rarer. We present a case of acute transverse myelitis after vaccination against COVID-19 with the ChAdOx1 nCOV-19 vaccine (AZD1222), which was the first case reported in Taiwan. Although it rarely occurs, post-vaccination neurological complications should not be ignored. As the pandemic of SARS-CoV-2 continues to spread and concern about vaccination efficacy and safety rises, heterologous vaccination were implemented in health public policy in several countries. A literature review of several clinical trials shows promising effects of mix-and-match vaccination. Further study on different combinations of vaccines can be expected.


Subject(s)
COVID-19 , Myelitis, Transverse , COVID-19 Vaccines , Humans , Myelitis, Transverse/chemically induced , SARS-CoV-2 , Vaccination/adverse effects
9.
J Pharm Anal ; 2021 Sep 16.
Article in English | MEDLINE | ID: covidwho-1415598

ABSTRACT

Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics. The surface spike protein, which plays a central role in virus infection, is currently the target for vaccines and neutralizing treatments. The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2 (ACE2). To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody (mAb) therapies, the binding activities of the original spike protein receptor binding domain (RBD) sequence and the reported spike protein variants were investigated using surface plasmon resonance (SPR). In addition, the interactions of the ACE2 receptor, an anti-spike monoclonal antibody (mAb1), a neutralizing monoclonal antibody (mAb2), the original spike RBD sequence, and mutants D614G, N501Y, N439K, Y453F, and E484K were assessed. Compared to the original RBD, the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity, whereas D614G had a substantial reduction in binding affinity. All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD, except for the E484K-mAb1 interaction. The potential neutralizing capability of mAb1 and mAb2 was investigated. Accordingly, mAb1 failed to inhibit the ACE2-RBD interaction and mAb2 inhibited the ACE2-RBD interactions for all RBD mutants, except mutant E484K, which only displayed partial blocking.

10.
Drug Evaluation Research ; 43(9):1706-1711, 2020.
Article in Chinese | GIM | ID: covidwho-1395263

ABSTRACT

Based on the patent information related to coronavirus vaccine, the present situation and development trend of coronavirus vaccine have been analyzed. Since the outbreak of SARS in 2002, the amount of patent applications of coronavirus vaccine reached the peak in 2003. Since the outbreak of Middle East respiratory syndrome in 2012, there was a small increase on the amount of patent applications of coronavirus vaccine from 2012 to 2015. In view of the analyses of the key applicants and vaccine types, it is concluded that nucleic acid vaccine, inactivated vaccine and viral vector vaccine are the main vaccine types against coronavirus, which is consistent with the three types of vaccines that have entered clinical trials in China and the United States.

11.
Lancet ; 398(10302): 747-758, 2021 08 28.
Article in English | MEDLINE | ID: covidwho-1376121

ABSTRACT

BACKGROUND: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. METHODS: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes. FINDINGS: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls. INTERPRETATION: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.


Subject(s)
COVID-19/complications , Survivors , Aged , Anxiety/etiology , COVID-19/physiopathology , COVID-19/psychology , Depression/etiology , Exercise Tolerance , Fatigue/etiology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lung/physiopathology , Male , Middle Aged , Muscle Weakness/etiology , Quality of Life , SARS-CoV-2 , Walk Test
12.
Int J Mol Sci ; 22(16)2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1367852

ABSTRACT

The SARS-CoV-2 pseudovirus is a commonly used strategy that mimics certain biological functions of the authentic virus by relying on biological legitimacy at the molecular level. Despite the fact that spike (S), envelope (E), and membrane (M) proteins together wrap up the SARS-CoV-2 virion, most of the reported pseudotype viruses consist of only the S protein. Here, we report that the presence of E and M increased the virion infectivity by promoting the S protein priming. The S, E, and M (SEM)-coated pseudovirion is spherical, containing crown-like spikes on the surface. Both S and SEM pseudoviruses packaged the same amounts of viral RNA, but the SEM virus bound more efficiently to cells stably expressing the viral receptor human angiotensin-converting enzyme II (hACE2) and became more infectious. Using this SEM pseudovirus, we examined the infectivity and antigenic properties of the natural SARS-CoV-2 variants. We showed that some variants have higher infectivity than the original virus and that some render the neutralizing plasma with lower potency. These studies thus revealed possible mechanisms of the dissemination advantage of these variants. Hence, the SEM pseudovirion provides a useful tool to evaluate the viral infectivity and capability of convalescent sera in neutralizing specific SARS-CoV-2 S dominant variants.


Subject(s)
Antibodies, Viral/metabolism , COVID-19/immunology , Coronavirus Envelope Proteins/metabolism , SARS-CoV-2/pathogenicity , Viral Matrix Proteins/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/virology , Cell Line , Coronavirus Envelope Proteins/genetics , Coronavirus Envelope Proteins/immunology , Coronavirus Envelope Proteins/ultrastructure , Cricetinae , Humans , Microscopy, Electron, Transmission , Mutation , Neutralization Tests , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Viral Matrix Proteins/ultrastructure , Virion/genetics , Virion/immunology , Virion/metabolism , Virion/ultrastructure
13.
Front Med (Lausanne) ; 8: 646506, 2021.
Article in English | MEDLINE | ID: covidwho-1323080

ABSTRACT

In the year 2020, the coronavirus disease 2019 (COVID-19) crisis intersected with the development and maturation of several digital technologies including the internet of things (IoT) with next-generation 5G networks, artificial intelligence (AI) that uses deep learning, big data analytics, and blockchain and robotic technology, which has resulted in an unprecedented opportunity for the progress of telemedicine. Digital technology-based telemedicine platform has currently been established in many countries, incorporated into clinical workflow with four modes, including "many to one" mode, "one to many" mode, "consultation" mode, and "practical operation" mode, and has shown to be feasible, effective, and efficient in sharing epidemiological data, enabling direct interactions among healthcare providers or patients across distance, minimizing the risk of disease infection, improving the quality of patient care, and preserving healthcare resources. In this state-of-the-art review, we gain insight into the potential benefits of demonstrating telemedicine in the context of a huge health crisis by summarizing the literature related to the use of digital technologies in telemedicine applications. We also outline several new strategies for supporting the use of telemedicine at scale.

14.
Chin J Acad Radiol ; : 1-9, 2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1286228

ABSTRACT

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P < 0.001) and more likely to be male (52.0% vs. 65.0%, P = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890], P < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all P < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1, P = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971, P = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387, P = 0.018). Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC. Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.

15.
Clin Infect Dis ; 71(16): 2158-2166, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153176

ABSTRACT

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan. Epidemiological and clinical characteristics of patients with COVID-19 have been reported, but the relationships between laboratory features and viral load has not been comprehensively described. METHODS: Adult inpatients (≥18 years old) with COVID-19 who underwent multiple (≥5 times) nucleic acid tests with nasal and pharyngeal swabs were recruited from Renmin Hospital of Wuhan University, including general patients (n = 70), severe patients (n = 195), and critical patients (n = 43). Laboratory data, demographic data, and clinical data were extracted from electronic medical records. The fitted polynomial curve was used to explore the association between serial viral loads and illness severity. RESULTS: Viral load of SARS-CoV-2 peaked within the first few days (2-4 days) after admission, then decreased rapidly along with virus rebound under treatment. Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads. The viral loads were higher in sputum compared with nasal and pharyngeal swab (P = .026). The positive rate of respiratory tract samples was significantly higher than that of gastrointestinal tract samples (P < .001). The SARS-CoV-2 viral load was negatively correlated with portion parameters of blood routine and lymphocyte subsets and was positively associated with laboratory features of cardiovascular system. CONCLUSIONS: The serial viral loads of patients revealed whole viral shedding during hospitalization and the resurgence of virus during the treatment, which could be used for early warning of illness severity, thus improve antiviral interventions.


Subject(s)
COVID-19/epidemiology , Coronavirus/pathogenicity , China/epidemiology , Female , Humans , Male , Serologic Tests , Viral Load
16.
Mol Biol Evol ; 38(7): 2715-2731, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1121171

ABSTRACT

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human angiotensin I converting enzyme 2 (ACE2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified nine ACE2 variants at ACE2-S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 nonhuman primates. Among the 6 apes and 20 Old World monkeys (OWMs) studied, we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by >50%. Based on these findings, we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.


Subject(s)
COVID-19 , Disease Resistance/genetics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Animals , COVID-19/genetics , COVID-19/immunology , Chlorocebus aethiops , Humans , Macaca mulatta , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology
17.
Front Immunol ; 11: 580237, 2020.
Article in English | MEDLINE | ID: covidwho-1116681

ABSTRACT

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results: The counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.


Subject(s)
CD8-Positive T-Lymphocytes/cytology , COVID-19/blood , Killer Cells, Natural/cytology , SARS-CoV-2/physiology , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , China/epidemiology , Female , Flow Cytometry , Humans , Killer Cells, Natural/immunology , Leukocyte Count , Male , Middle Aged , Pandemics , Prognosis , SARS-CoV-2/genetics , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology
18.
J Nat Prod ; 84(2): 436-443, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1072094

ABSTRACT

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 µM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 µM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that 4 and 5 are potential SARS-CoV-2 entry inhibitors.


Subject(s)
Hypocreales/chemistry , Naphthoquinones/pharmacology , Perylene/analogs & derivatives , Quinones/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Naphthoquinones/chemistry , Perylene/chemistry , Perylene/pharmacology , Quinones/chemistry , SARS-CoV-2/physiology
19.
Biomed Environ Sci ; 33(12): 893-905, 2020 Dec 20.
Article in English | MEDLINE | ID: covidwho-1060079

ABSTRACT

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.


Subject(s)
COVID-19/complications , Adult , Aged , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome
20.
J Craniofac Surg ; Publish Ahead of Print2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1020334

ABSTRACT

ABSTRACT: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2) emerged in Wuhan City. The present study aimed to assess the demographic variables, causes, and patterns of maxillofacial injuries managed at a teaching hospital in Wuhan City during the transmission control measures in the coronavirus disease 2019 (COVID-19) epidemic. In this retrospective study, all patients treated for maxillofacial injuries in the hospital between January 23 and April 7 (2019 and 2020) were involved. Epidemiologic information, including the number of patients, gender, age, etiology, time since injury to the clinic visit, and type of maxillofacial injuries, was recorded. Data of the 2 periods (2019 and 2020) were compared and analyzed. A total of 337 patients had maxillofacial injuries at the 2-time intervals: 74 in 2020 and 263 in 2019. The characteristics of maxillofacial injuries had changes during the transmission control measures in the COVID-19 epidemic, which included the number of patients, gender, age, etiology, time since injury to the clinic visit, and type of maxillofacial injuries. The transmission control measures during the COVID-19 epidemic had a significant impact on the epidemiology of maxillofacial injuries in Wuhan City.

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