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2.
Front Cell Infect Microbiol ; 11: 613304, 2021.
Article in English | MEDLINE | ID: covidwho-1088903

ABSTRACT

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.


Subject(s)
/methods , Real-Time Polymerase Chain Reaction/methods , /genetics , /virology , /genetics , DNA Primers/genetics , Humans , Phosphoproteins/genetics , Point-of-Care Testing , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction/instrumentation , Recombinases/metabolism , Reverse Transcription , Sensitivity and Specificity
3.
JAMA Netw Open ; 4(1): e2034569, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1049542

ABSTRACT

Importance: Acute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis. Objective: To systematically evaluate the association of blood metabolites with ARDS risk and survival. Design, Setting, and Participants: In this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019. Main Outcomes and Measures: Participants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival. Results: Of the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = 7.46 × 10-6) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97; P = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56; P = 6.95 × 10-4) and 60-day (OR, 0.36; 95% CI, 0.19-0.71; P = 3.12 × 10-3) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74; P = 6.41 × 10-4) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80; P = 2.11 × 10-3) survival. Conclusions and Relevance: In this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.


Subject(s)
Mannose/blood , /mortality , APACHE , Aged , Critical Illness , Female , Humans , Intensive Care Units , Logistic Models , Male , Mendelian Randomization Analysis , Middle Aged , Patient Admission/statistics & numerical data , Prognosis , Proportional Hazards Models , Prospective Studies , Risk Assessment
4.
Preprint | SciFinder | ID: ppcovidwho-5248

ABSTRACT

The study was designed to explore the mol mechanism of Huopuxialing Decoction for the treatment of corona virus disease (COVID-19) based on network pharmacol , and provide new ideas for its clin treatment and laboratory research The results show Huopuxialing Decoction may treat COVID-19 by intervening inflammatory response, immune regulation and apoptosis through multiple targets and multiple pathways

5.
BMC Public Health ; 20(1): 1649, 2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-909100

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that spreads around the world. The lack of effective antiviral drugs and vaccines, along with the relatively high mortality rate and high contagiousness, has raised strong public concerns over COVID-19, especially for people living in the most severely affected areas. This study aimed to clarify the influencing factors for the anxiety level among the Chinese people during the COVID-19 pandemic, with a particular focus on the media exposure to different COVID-19 information. METHODS: A total of 4991 respondents were randomly recruited from a national online panel from February 12th, 2020 to February 14th, 2020, a period when the number of COVID-19 cases surpassed 10,000 in a single day, with the total cases in China reaching up to 90,000. The relationships between media exposure of COVID-19 information, social and geographical proximity to COVID-19, risk perceptions were assessed using hierarchical ordinary least squares regression analysis. RESULTS: The media exposure to COVID-19 information was differently associated with anxiety. Meanwhile, the anxiety level was found to be high in respondents who personally knew someone infected with COVID-19 or those who living in an area with reported cases. Respondents who perceived more risks also reported a higher level of anxiety. CONCLUSIONS: This study highlights the role of media exposure in affecting individuals' anxiety level during the COVID-19 pandemic. Besides, it is recommended that government and health professionals are recommended to adopt effective risk communication strategies to protect citizens' mental health during the pandemic.


Subject(s)
Anxiety/epidemiology , Consumer Health Information/statistics & numerical data , Coronavirus Infections/epidemiology , Mass Media/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , Adolescent , Adult , China/epidemiology , Diagnostic Self Evaluation , Female , Humans , Interpersonal Relations , Male , Middle Aged , Residence Characteristics/statistics & numerical data , Risk Assessment , Young Adult
7.
EBioMedicine ; 57:102843-102843, 2020.
Article in English | WHO COVID | ID: covidwho-662214

ABSTRACT

BACKGROUND: Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD) Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown We aimed to identify a CNV associated with BrS and elucidated its clinical implications METHODS: We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase HEK cells and zebrafish were used to characterize the function of the CNV variant FINDINGS: A copy number deletion of GSTM3 (chr1:109737011-109737301, hg38) containing the eighth exon and the transcription stop codon was observed in 23 9% of BrS patients versus 0 8% of 15,829 controls in Taiwan Biobank (P <0 001), and 0% in gnomAD Co-segregation analysis showed that the co-segregation rate was 20% Patch clamp experiments showed that in an oxidative stress environment, GSTM3 down-regulation leads to a significant decrease of cardiac sodium channel current amplitude Ventricular arrhythmia incidence was significantly greater in gstm3 knockout zebrafish at baseline and after flecainide, but was reduced after quinidine, consistent with clinical observations BrS patients carrying the GSTM3 deletion had higher rates of sudden cardiac arrest and syncope compared to those without (OR: 3 18 (1 77-5 74), P<0 001;OR: 1 76 (1 02-3 05), P = 0 04, respectively) INTERPRETATION: This GSTM3 deletion is frequently observed in BrS patients and is associated with reduced INa, pointing to this as a novel potential genetic modifier/risk predictor for the development of the electrocardiographic and arrhythmic manifestations of BrS FUNDING: This work was supported by the Ministry of Science and Technology (107-2314-B-002-261-MY3 to J M J Juang), and by grants HL47678, HL138103 and HL152201 from the National Institutes of Health to CA

8.
Geriatr Gerontol Int ; 20(10): 938-942, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-744733

ABSTRACT

AIM: The policy enforcing visiting restriction during the COVID-19 pandemic may cause feelings of social isolation among residents in long-term care facilities. This study aimed to explore family members' concerns for their relatives during the lockdown period, assess their level of acceptance of the visiting restriction policy and determine the associated factors. METHODS: From the 156 family members interviewed, demographic data, satisfaction with overall care quality, worry and concerns for their relatives, acceptance of the visiting restriction and arrangement for the residents if cluster infections occur in the facility were recorded. RESULTS: Among the members interviewed, 83 (53.2%) were men; mean age of members was 56.3 ± 9.8; most were offspring of residents in the facility (n = 121, 77.6%), most visited the residents at least once a week (n = 113, 72.4%) before the lockdown. The most common concerns of the family members for their relatives were psychological stress (38.5%), followed by nursing care (26.9%) and daily activity (21.1%). Nearly 84.6% of those interviewed accepted the visiting restriction policy, and a higher satisfaction rating independently associated with acceptance of the visiting restriction policy (odds ratio 2.15). CONCLUSIONS: During the lockdown period, staff members should provide more psychological information about residents to their family members. Higher satisfaction rating was found to be independent of the acceptance of the visiting restriction policy. Therefore, good quality of care of the facility wins the trust of family members, and this might mitigate the tension between the family members and staff during a major crisis. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; 20: 938-942.


Subject(s)
Coronavirus Infections/psychology , Family/psychology , Homes for the Aged , Nursing Homes , Pneumonia, Viral/psychology , Visitors to Patients/psychology , Adult , Aged , Aged, 80 and over , Betacoronavirus , Female , Humans , Long-Term Care , Male , Middle Aged , Pandemics , Personal Satisfaction , Professional-Family Relations , Social Isolation , Stress, Psychological , Taiwan
9.
Int J Antimicrob Agents ; 56(3): 106103, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-664350

ABSTRACT

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Antiviral Agents/administration & dosage , Coronavirus Infections/therapy , Immunologic Factors/administration & dosage , Pneumonia, Viral/therapy , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/adverse effects , Bacterial Infections/diagnosis , Bacterial Infections/etiology , Bacterial Infections/immunology , Bacterial Infections/mortality , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Drug Administration Schedule , Humans , Immunologic Factors/adverse effects , Intensive Care Units , Opportunistic Infections/diagnosis , Opportunistic Infections/etiology , Opportunistic Infections/immunology , Opportunistic Infections/mortality , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiration, Artificial , Retrospective Studies , Severity of Illness Index , Survival Analysis , Treatment Outcome
11.
Acta Pharm Sin B ; 10(7): 1205-1215, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-88716

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

12.
J Clin Med ; 9(4)2020 Apr 15.
Article in English | MEDLINE | ID: covidwho-60425

ABSTRACT

An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.

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