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1.
Sci Rep ; 13(1): 4159, 2023 03 13.
Article in English | MEDLINE | ID: covidwho-2274169

ABSTRACT

Severe Covid-19 may cause a cascade of cardiovascular complications beyond viral pneumonia. The severe inflammation may affect the microcirculation which can be assessed by cardiovascular magnetic resonance (CMR) imaging using quantitative perfusion mapping and calculation of myocardial perfusion reserve (MPR). Furthermore, native T1 and T2 mapping have previously been shown to identify changes in myocardial perfusion by the change in native T1 and T2 during adenosine stress. However, the relationship between native T1, native T2, ΔT1 and ΔT2 with myocardial perfusion and MPR during long-term follow-up in severe Covid-19 is currently unknown. Therefore, patients with severe Covid-19 (n = 37, median age 57 years, 24% females) underwent 1.5 T CMR median 292 days following discharge. Quantitative myocardial perfusion (ml/min/g), and native T1 and T2 maps were acquired during adenosine stress, and rest, respectively. Both native T1 (R2 = 0.35, p < 0.001) and native T2 (R2 = 0.28, p < 0.001) correlated with myocardial perfusion. However, there was no correlation with ΔT1 or ΔT2 with MPR, respectively (p > 0.05 for both). Native T1 and native T2 correlate with myocardial perfusion during adenosine stress, reflecting the coronary circulation in patients during long-term follow-up of severe Covid-19. Neither ΔT1 nor ΔT2 can be used to assess MPR in patients with severe Covid-19.


Subject(s)
COVID-19 , Female , Humans , Middle Aged , Male , Follow-Up Studies , Predictive Value of Tests , Adenosine , Magnetic Resonance Imaging , Coronary Circulation , Magnetic Resonance Imaging, Cine/methods
2.
Soc Psychol Educ ; : 1-15, 2023 Mar 27.
Article in English | MEDLINE | ID: covidwho-2286017

ABSTRACT

The changes that COVID-19 pandemic has brought upon the world are unprecedented. Its impact on students' learning is equally profound, making it critical to heed students' academic achievement effects that may derive from these alterations. Therefore, the present study explored an integrative model of mental health, self-regulated learning and academic achievement among adolescents during the pandemic. Participants were 1001 senior high school students (Mage = 17.00, SDage = 0.78, 48.7% female) from China. Results showed that the degree to which students were mentally healthy was not significantly related to academic achievement, whereas academic achievement and mental health were positively associated with self-regulated learning. Following structural equation modelling analysis, the effect of mental health on academic achievement was fully mediated by self-regulated learning. Taken together, the findings emphasised the necessity of developing self-regulated learning strategies during public health emergencies and have clinical and educational implications for planning psychological interventions in order to improve mental health and academic performance as well.

3.
AIDS Patient Care STDS ; 2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-2116972

ABSTRACT

The COVID-19 pandemic has created additional barriers to accessing sexual health services among gay, bisexual, and other men who have sex with men (GBMSM) in China. Yet, little is known about the frequency of HIV testing and how GBMSM get tested during the pandemic. We surveyed an online sample of GBMSM recruited on a gay networking app in China. Among 956 sexually active, 70.1% had received an HIV test in the past 6 months. Among these, 61.0% reported having undergone HIV self-testing (HIVST). Young GBMSM aged 18-24 years old were more likely to receive a recent HIV test, and the number of sexual partners was associated with recent HIV testing [adjusted odds ratio (AOR) = 1.14, 95% confidence interval (CI): 1.03-1.20]. Among those who had a recent HIV test, young GBMSM and those who had anal sex with both main partner and casual partners were more likely to utilize HIVST (AOR = 1.83, 95% CI: 1.16-2.84), as well as GBMSM who did not use a condom the last time engaged in anal sex (AOR = 1.57, 95% CI: 1.06-2.34). Among GBMSM never tested for HIV, a majority perceived low risk of HIV, while some suggested that they did not know where to get tested or they were scared of finding out they had HIV. HIVST has the potential to fill the gap in HIV testing among Chinese GBMSM, and future HIV testing programs should emphasize HIV education, accurate information dissertation, and timely point-to-care services.

4.
Sci Rep ; 12(1): 19165, 2022 Nov 10.
Article in English | MEDLINE | ID: covidwho-2118041

ABSTRACT

Machine learning methods are a novel way to predict and rank donors' willingness to donate blood and to achieve precision recruitment, which can improve the recruitment efficiency and meet the challenge of blood shortage. We collected information about experienced blood donors via short message service (SMS) recruitment and developed 7 machine learning-based recruitment models using PyCharm-Python Environment and 13 features which were described as a method for ranking and predicting donors' intentions to donate blood with a floating number between 0 and 1. Performance of the prediction models was assessed by the Area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score in the full dataset, and by the accuracy in the four sub-datasets. The developed models were applied to prospective validations of recruiting experienced blood donors during two COVID-19 pandemics, while the routine method was used as a control. Overall, a total of 95,476 recruitments via SMS and their donation results were enrolled in our modelling study. The strongest predictor features for the donation of experienced donors were blood donation interval, age, and donation frequency. Among the seven baseline models, the eXtreme Gradient Boosting (XGBoost) and Support vector machine models (SVM) achieved the best performance: mean (95%CI) with the highest AUC: 0.809 (0.806-0.811), accuracy: 0.815 (0.812-0.818), precision: 0.840 (0.835-0.845), and F1 score of XGBoost: 0.843 (0.840-0.845) and recall of SVM: 0.991 (0.988-0.994). The hit rate of the XGBoost model alone and the combined XGBoost and SVM models were 1.25 and 1.80 times higher than that of the conventional method as a control in 2 recruitments respectively, and the hit rate of the high willingness to donate group was 1.96 times higher than that of the low willingness to donate group. Our results suggested that the machine learning models could predict and determine the experienced donors with a strong willingness to donate blood by a ranking score based on personalized donation data and demographical details, significantly improve the recruitment rate of blood donors and help blood agencies to maintain the blood supply in emergencies.


Subject(s)
Blood Donors , COVID-19 , Humans , COVID-19/epidemiology , Machine Learning , Intention , Disease Outbreaks
5.
PLoS One ; 17(9): e0275209, 2022.
Article in English | MEDLINE | ID: covidwho-2054362

ABSTRACT

BACKGROUND: Adherence to oral nutritional supplement therapy among postoperative patients with gastric cancer is low. There is little knowledge about patients' priorities and needs regarding oral nutritional supplement therapy. The discrete choice experiment is an innovative method used to elicit patients' preferences. Good practice guidelines emphasize that the development of attributes and levels is a fundamentally important process. OBJECTIVE: To comprehensively describe the identification, refinement, and selection of attributes and levels for a discrete choice experiment. METHODS: A mixed-methods approach, consisting of three consecutive steps: a literature review, in-depth interviews, and focus groups. First, the literature review allowed quick identification of attributes and levels. Then, 15 in-depth interviews were conducted to gather a rich description of the experience of patients taking oral nutritional supplements after gastrectomy and to verify and enrich the attributes and levels list. Finally, four focus group participants discussed the wording of the attributes and levels and reduced the number of attributes to manageable numbers through voting ranking methods. RESULTS: Following the literature review and qualitative data collection, eight attributes were finally generated, each with two to three levels. The following attributes were included: 1) information provider; 2) health guidance approach; 3) adverse reactions; 4) flavor; 5) follow-up method; 6) follow-up frequency; 7) psychological support; 8) cost. These attributes covered the important attributes of nutritional preparations and health guidance included in ONS therapy that were relevant to patients. CONCLUSIONS: This study's mixed-methods approach has been found highly suitable to identify, refine and select attributes and levels for a discrete choice experiment. The three methods have pros and cons, and they complement each other, especially the analysis of qualitative data led to a deeper and broader understanding of attributes and levels.


Subject(s)
Stomach Neoplasms , Behavior Therapy , Gastrectomy , Humans , Nutritional Support , Postoperative Period , Stomach Neoplasms/surgery
6.
J Virol ; 96(20): e0131822, 2022 10 26.
Article in English | MEDLINE | ID: covidwho-2053123

ABSTRACT

Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through in vitro coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis; in vivo, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention. IMPORTANCE Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last, in vivo, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.


Subject(s)
COVID-19 , Herpesvirus 1, Suid , Pseudorabies , Mice , Humans , Animals , Herpesvirus 1, Suid/metabolism , Neuropilin-1/genetics , Neuropilin-1/metabolism , Furin/metabolism , SARS-CoV-2 , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Virus Replication , Viral Proteins/metabolism , Antiviral Agents/metabolism , Mammals
7.
J Biol Chem ; 298(11): 102511, 2022 11.
Article in English | MEDLINE | ID: covidwho-2031421

ABSTRACT

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus/metabolism , Cell Fusion , Virus Internalization , Serine Proteases
8.
J Cardiovasc Magn Reson ; 24(1): 50, 2022 09 12.
Article in English | MEDLINE | ID: covidwho-2021309

ABSTRACT

BACKGROUND: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. METHODS: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. RESULTS: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. CONCLUSIONS: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.


Subject(s)
COVID-19 , Myocarditis , COVID-19/complications , Case-Control Studies , Contrast Media , Gadolinium , Humans , Magnetic Resonance Imaging , Predictive Value of Tests , Spectrum Analysis , Post-Acute COVID-19 Syndrome
9.
Front Psychiatry ; 13: 805512, 2022.
Article in English | MEDLINE | ID: covidwho-1952702

ABSTRACT

Aims: To explore the public's preference for psychological interventions through a discrete choice experiment and to provide references for formulating psychological intervention policies and establishing psychological intervention procedures in response to public health emergencies. Methods: This study is a discrete choice experiment. Attributes and levels were identified through literature reviews, in-depth interviews, focus group discussions, and expert consultations. Experimental design principles were applied to generate choice sets containing different attribute levels and develop a survey instrument. Convenience sampling was conducted nationwide, and 1,045 participants were investigated. A mixed logit model was used to evaluate the public's preferences. Results: All attributes in our study were found to have a significant influence on the public's preferences for psychological interventions during the COVID-19 pandemic. The public's preferences for providers and duration were influenced by the public's levels of education and classifications. Furthermore, the most ideal scenario was found to be a one-on-one psychological intervention provided by family and friends through social network platforms, for which the frequency is twice per week, and the duration of each intervention is 0.5-1 h. Conclusions: The public's preferences for psychological interventions during the COVID-19 pandemic are affected by the method, form, frequency, provider, and duration of interventions. Our findings provide references for the formulation of psychological intervention policies and the establishment of psychological intervention procedures in response to public health emergencies.

10.
J Psychiatr Res ; 154: 198-202, 2022 10.
Article in English | MEDLINE | ID: covidwho-1936863

ABSTRACT

Population-based measures and public health response to stem the spread of the coronavirus may have caused unintended isolation and increased the risk of psychiatric illnesses. The objective of this study is to assess psychological distress among gay, bisexual, and other men who have sex with men (MSM) in China during the COVID-19 pandemic and examine whether these mental health outcomes differ by HIV status. Data were derived from a cross-sectional survey on the impact of COVID-19 on users of Blued, the largest gay social networking app in July 2020. All active users on Blued were invited to complete a survey regarding sexual behaviors, HIV prevention and treatment service utilization, and various health and mental health outcomes. Among all participants (n = 1205), over half (53.2%) of the participants screened mild to severe psychological distress: 34.9% screened mild, 11.6% screened moderate, and 6.6% screened severe psychological distress. Of all participants, 20.9% met the criteria for anxiety and 19.6% for depression. Psychological distress was associated with younger age having a degree below college, being unemployed, and having lower income. MSM with HIV were more likely to report depression or anxiety compared to HIV negative/unknown status MSM after adjusting for study covariates (AOR = 1.80, 95%CI 1.01-3.26; AOR = 2.04, 95%CI 1.11-3.67, respectively). MSM in China experience a high burden of psychological distress during the COVID-19 pandemic. Integrated HIV treatment and mental health services are needed to provide adequate and timely mental health support to MSM living with HIV.


Subject(s)
COVID-19 , HIV Infections , Sexual and Gender Minorities , COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , HIV Infections/epidemiology , HIV Infections/psychology , Homosexuality, Male/psychology , Humans , Male , Mental Health , Pandemics , Sexual Behavior/psychology
11.
Heart ; 108(Suppl 1):A116, 2022.
Article in English | ProQuest Central | ID: covidwho-1891872

ABSTRACT

150 Table 1Comparison of 31P-MRS and CMR findings between patients with Post-COVID-19 syndrome and healthy volunteersVariable Healthy volunteers (n=10) Post-COVID-19 Syndrome (n=19) p-value PCr/ATP ratio 2.11±0.5 2.24±0.4 0.49 LV end diastolic volume index (ml/m2) 87±20 81±10 0.43 LV ejection fraction (%) 64±4 61±4 0.07 RV end diastolic volume index (ml/m2) 93±23 83±13 0.24 RV ejection fraction (%) 55±8 57±6 0.49 Global longitudinal strain (%) -13.3±2.3 -11.9±3.7 0.21 Mean T1 (ms) 1206±64 1158±114 0.15 Extra-cellular volume (%) 25±2.3 22±4.5 0.03 T2 (ms) 39±2.4 40±2.9 0.46 MPR 3.1±0.9 3.0±0.8 0.89 Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as number (%). PCr/ATP=phosphocreatine and adenosine triphosphate ratio;LV=left ventricular;ml/m2=milliliters per square meter of body surface area;RV=right ventricular;ms=milliseconds;MPR=myocardial perfusion reserve. 150 Figure 1Evaluation of Cardiac Involvement in Post COVID-19 Syndrome[Figure omitted. See PDF]Conflict of InterestNone

12.
Aging (Albany NY) ; 14(10): 4211-4219, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1856446

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Shock, Septic , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , China/epidemiology , Humans , Multiple Organ Failure , SARS-CoV-2 , Vaccines, Inactivated
13.
Arch Virol ; 167(2): 493-499, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1712247

ABSTRACT

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10-1 median tissue culture infection dose (TCID50) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were < 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field.


Subject(s)
Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Porcine Reproductive and Respiratory Syndrome/diagnosis , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/metabolism , Recombinases , Reverse Transcription , Sensitivity and Specificity , Swine
14.
Front Cardiovasc Med ; 8: 764599, 2021.
Article in English | MEDLINE | ID: covidwho-1598692

ABSTRACT

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis. Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients. Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF. Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54-71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29-146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01). Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

15.
Nature ; 593(7859): 418-423, 2021 05.
Article in English | MEDLINE | ID: covidwho-1137788

ABSTRACT

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.


Subject(s)
Antiviral Agents/pharmacology , Clofazimine/pharmacology , Coronavirus/classification , Coronavirus/drug effects , SARS-CoV-2/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Biological Availability , Cell Fusion , Cell Line , Clofazimine/pharmacokinetics , Clofazimine/therapeutic use , Coronavirus/growth & development , Coronavirus/pathogenicity , Cricetinae , DNA Helicases/antagonists & inhibitors , Drug Synergism , Female , Humans , Life Cycle Stages/drug effects , Male , Mesocricetus , Pre-Exposure Prophylaxis , SARS-CoV-2/growth & development , Species Specificity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Transcription, Genetic/drug effects , Transcription, Genetic/genetics
16.
Eur Heart J ; 42(19): 1866-1878, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1087735

ABSTRACT

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.


Subject(s)
COVID-19 , Myocarditis , Contrast Media , Female , Gadolinium , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Male , Myocarditis/diagnostic imaging , Myocardium , Predictive Value of Tests , SARS-CoV-2 , Troponin , Ventricular Function, Left
18.
BMC Psychiatry ; 21(1): 34, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1059596

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly in China and other overseas areas, which has aroused widespread concern. The sharp increase in the number of patients has led to great psychological pressure on health care workers. The purpose of this study was to understand their mental health status and needs, so as to provide a scientific basis for alleviating the psychological pressure of health care workers. METHODS: Using a cross-sectional study design, 540 health care workers were randomly selected from two designated tuberculosis medical institutions in Anhui Province. The basic situation, perceived social support, depression level, loneliness and COVID-19 related knowledge were collected and analyzed by questionnaire. RESULTS: A total of 511 valid questionnaires were finally retrieved. There were 139 people in epidemic prevention and control positions (27.20%). Depression level: People in isolation ward, fever clinic and pre-check triage were at the level of mild to moderate depression. Female was higher than male; nurse was higher than doctor; middle and junior job titles were higher than senior titles; junior college degree or below were higher than bachelor's degree, master's degree and above; isolation ward, fever clinic and pre-check triage were significantly higher than those of non-prevention and control positions (p < 0.05). Loneliness scores: Doctors were higher than that of medical technicians, and isolation ward, fever clinic and pre-check triage were higher than those of other medical departments (p < 0.05). Social support: Doctors were lower than that of medical technicians, and isolation ward, fever clinic and pre-check triage were significantly lower than those of other departments (p < 0.05). The score of social support was negatively correlated with depression and loneliness (p < 0.001), while depression was positively correlated with loneliness (p < 0.001). Health care workers most want to receive one-to-one psychological counseling (29.75%), and provide crisis management (24.07%). The awareness rate of health care workers on COVID-19's knowledge was relatively high. CONCLUSIONS: The psychological problems of health care workers, especially women, nurses with low educational background, low professional title, and staff in the epidemic prevention and control positions are relatively serious.


Subject(s)
COVID-19 , Mental Health , Anxiety , Asian People , China , Cross-Sectional Studies , Depression , Female , Health Personnel , Humans , Male , SARS-CoV-2 , Social Support , Surveys and Questionnaires
19.
Clin Med (Lond) ; 21(1): e80-e83, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1000587

ABSTRACT

AIM: The inconsistent effects of lopinavir-ritonavir (LPV/r) on COVID-19 seem to be caused by the therapeutic window. In the present study, we aim to present the effects of early LPV/r treatment on patients with severe COVID-19. METHODS: The demographics, characteristics, treatments, SARS-CoV-2 test results and outcomes of 19 patients with severe COVID-19 treated with LPV/r within 12 days of onset of symptoms were retrospectively assessed. RESULTS: Within 3 days of admission, three (15.79%) patients received noninvasive ventilation, and 16 (84.21%) patients received high-flow oxygen support. The median duration between the onset of symptoms and initiating LPV/r therapy was 9 (range 2-12) days. The median course of LPV/r treatment was 11 (range 7-17) days. One of the 19 patients (5.26%) died. Of the 18 patients discharged, the median hospital stay was 17 (range 11-45) days. At day 6 after LPV/r therapy was initiated, 68.42% of patients were virologically cured, increasing to 84.22% at day 12. CONCLUSION: In this cohort of patients with severe COVID-19 who were treated with LPV/r within 12 days of the onset of symptoms, clinical improvement was observed in 18/19 patients (94.74%). Randomised controlled trials are urgently needed to further evaluate this strategy.


Subject(s)
COVID-19 Drug Treatment , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Cytochrome P-450 CYP3A Inhibitors/therapeutic use , Drug Combinations , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Treatment Outcome , Young Adult
20.
Zool Res ; 41(5): 517-526, 2020 Sep 18.
Article in English | MEDLINE | ID: covidwho-671953

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5-6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days post-inoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/growth & development , Coronavirus Infections/diagnosis , Disease Models, Animal , Lung/pathology , Pneumonia, Viral/diagnosis , Tupaiidae/physiology , Age Factors , Animals , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Humans , Lung/virology , Male , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Tupaiidae/virology , Virus Shedding/physiology
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