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1.
J Glob Health ; 11: 05023, 2021.
Article in English | MEDLINE | ID: covidwho-1573936

ABSTRACT

Background: In response to the COVID-19 pandemic, two new temporary hospitals were constructed in record time in Wuhan, China, to help combat the fast-spreading virus in February 2020. Using the experience of one of the hospitals as a case study, we discuss the health and economic implications of this response strategy and its potential application in other countries. Methods: This retrospective observational study analyzed health resource utilization and clinical outcomes data for 2011 inpatients diagnosed with COVID-19 and admitted to Leishenshan Hospital during its 67 days of operation from February 8th to April 14th, 2020. We used a top-down costing approach to estimate the total cost of treating patients at the Leishenshan Hospital, including capital cost for hospital construction, health personnel costs, and direct health care costs. We used a multivariate generalized linear model to examine risk factors associated with in-hospital deaths. Results: During the 67 days of hospital operation, 19 medical teams comprising of 933 doctors and 2312 nurses were gradually transferred to Leishenshan Hospital from across China. Of the 2011 admissions, 4.5% used intensive care and 2.0% used ventilators. Overall median length of stay was 19 days, and 21 days for patients in the intensive care unit (ICU). The case fatality rate (CFR) was 2.3% overall, 41.8% in the ICU, and 0.4% in general ward (GW). CFRs were 55% and 50% among patients using non-invasive and invasive ventilators, respectively. The mean total cost and direct health care cost were CNY806 997 (US$114 793) and CNY16 087 (US$2288), respectively. Patients admitted to the ICU had much higher direct health care costs, on average, compared to those in the GW (CNY150 415 vs CNY9720, or US$21 396 vs US$1383). The mean direct health care cost per patient with severe or critical diseases was more than five times higher than those with mild or moderate diseases (CNY45 191 vs CNY8838, or US$6428 vs US$1257). Older age, having comorbidities, and critical disease were associated with higher risks of death from COVID-19. Lower health worker to patient ratio (<2.6) was not associated with in-hospital death. Conclusion: An adequate health workforce were mobilized and deployed to a new temporary hospital. The Leishenshan Hospital increased access to care during the surge in COVID-19 infections, facilitated timely treatment, and transferred COVID-19 patients between GWs and ICUs within the hospital, all of which are potential contributors to lowering the CFR. Patients in the ICU experienced a much higher CFR and a greater burden of health care cost than those in GW. Our results have important implications for other countries interested in constructing temporary emergency hospitals, such as the need for adequate infrastructure capacities and financial support, centralized strategies to mobilize health workforce and to provide respiratory protective devices, and improvement in access to health care.


Subject(s)
COVID-19 , Aged , Hospital Mortality , Hospitals , Humans , Mobile Health Units , Pandemics , SARS-CoV-2
2.
Am J Infect Control ; 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1557001

ABSTRACT

BACKGROUND: Hand hygiene (HH) is a cost-effective measure to reduce healthcare-associated infections. The overall characteristics and changes of hand hygiene compliance (HHC) among healthcare providers during the COVID-19 pandemic provided evidence for targeted HH intervention measures. AIM: To systematically review the literature and conduct a meta-analysis of studies investigating the rate of HHC and the characteristics of HH during the COVID-19 pandemic. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang Data, VIP and CBM databases were searched. All the original articles with valid HHC data among healthcare providers during the COVID-19 pandemic (from January 1, 2020 to October 1, 2021) were included. Meta-analysis was performed using a DerSimonian and Laird model to yield a point estimate and a 95% CI for the HHC rate. The heterogeneity of the studies was evaluated using the Cochrane Q test and I2 statistics and a random-effects model was used to contrast between different occupations, the WHO five-moments of HH and different observation methods. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. FINDINGS: Seven studies with 2377 healthcare providers reporting HHC were identified. The estimated overall HHC was 74%, which was higher than that reported in previous studies (5%-89%). Fever clinic has become a new key place for HHC observation. Nurses had the highest HHC (80%; 95% CI:74%-87%) while auxiliary workers (70%; 95%CI:62%-77%) had the lowest. For the WHO five-moments, the healthcare providers had the highest HHC after contact with the body fluids of the patients (91%; 95% CI:88%-94%), while before contact with patients healthcare providers had the lowest HHC (68%; 95% CI:62%-74%) which was consistent with before the pandemic. There existed great HHC differences among different monitoring methods (automatic monitoring system:53%; 95% CI:44%-63% vs openly and secretly observation: 91%; 95% CI: 90%-91%). CONCLUSIONS: During the COVID-19 pandemic, the compliance of healthcare providers' HH showed a great improvement. The fever clinics have become the focused departments for HH monitoring. The HHC of auxiliary workers and the HH opportunity for "before contact with patients" should be strengthened. In the future, it will be necessary to develop standardized HH monitoring tools for practical work.

3.
Diabetes Metab Syndr Obes ; 14: 4469-4482, 2021.
Article in English | MEDLINE | ID: covidwho-1526719

ABSTRACT

Purpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD). Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers. Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49-4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21-183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01-0.56; P < 0.001). Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.

4.
J Infect Public Health ; 15(1): 13-20, 2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1517346

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49-75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. METHODS: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. RESULTS: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00-56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. CONCLUSIONS: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

5.
Front Med (Lausanne) ; 8: 614057, 2021.
Article in English | MEDLINE | ID: covidwho-1485065

ABSTRACT

Objective: This study aimed to determine the association between prognosis of COVID-19 patients with and without cancer. Moreover, we compared the prognosis of cancer patients subjected to anti-tumor therapy with those who have not undergone anti-tumor therapy in the past 6 months. Methods and Results: A total of 7,926 adult patients with COVID-19 were retrospectively enrolled in Hubei Province,China between December 31, 2019 and February 20, 2020. Two hundred and seventy seven cancer patients (cancer group, median age 64 [IQR 56-70] years; 50.90% male) and 7,649 non-cancer patients were identified (non-cancer group, median age 55 [IQR 42-64] years; 48.19% male). The mortality rate was lower in the non-cancer group compared to the cancer group (4.50 vs. 9.03%; P < 0.001). The duration between onset and admission shorter in the cancer group (Days, 9 [IQR 5-18]) compared to the non-cancer group (Days, 10; [IQR 6-19]; P = 0.036). ICU occupancy was higher in the cancer group (n[%], 30[10.83%]) than in the non-cancer group (n[%], 314[4.11%]). In reviewing the anti-tumor therapy, data from 277 selected cancer patients were obtained out of which 74 patients had undergone anti-tumor therapy (mean age 65 [IQR 51-67] years; 45.95% male), 203 had not undergone anti-tumor therapy (non-anti-tumor therapy group, mean age 63 [IQR 53-75] years; 49.75% male) in the past 6 months. The mortality rate for the anti-tumor therapy group and the non-anti-tumor therapy group was similar (9.46 vs. 8.87%; P = 0.879). Conclusion: The mortality rate was higher in COVID-19 patients with cancer compared to those without cancer. Moreover, anti-tumor therapy in the past 6 months did not worsen the prognosis of cancer patients with COVID-19.

7.
Signal Transduct Target Ther ; 6(1): 347, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1437669

ABSTRACT

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Basigin/antagonists & inhibitors , Basigin/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , COVID-19/genetics , Chlorocebus aethiops , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
8.
Respir Res ; 22(1): 21, 2021 Jan 19.
Article in English | MEDLINE | ID: covidwho-1388765
9.
Front Cardiovasc Med ; 8: 654405, 2021.
Article in English | MEDLINE | ID: covidwho-1247849

ABSTRACT

Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients. Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed. Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro-B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement-negative subgroup. Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

10.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Article in English | MEDLINE | ID: covidwho-1137872

ABSTRACT

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Subject(s)
COVID-19 , Risk Assessment/methods , COVID-19/epidemiology , COVID-19/mortality , China , Hospitalization/statistics & numerical data , Humans , Italy , Risk Factors
11.
Hepatology ; 73(1): 470-471, 2021 01.
Article in English | MEDLINE | ID: covidwho-1098892

Subject(s)
COVID-19 , Humans , Liver , SARS-CoV-2
12.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1064967

ABSTRACT

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Lymphocytes/cytology , Neutrophils/cytology , Adrenal Cortex Hormones/adverse effects , Area Under Curve , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Length of Stay , Proportional Hazards Models , ROC Curve , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Rate , Treatment Outcome
13.
Med (N Y) ; 2(4): 435-447.e4, 2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1057073

ABSTRACT

Background: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). Methods: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). Findings: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. Conclusions: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. Funding: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

15.
Hypertension ; 76(4): 1104-1112, 2020 10.
Article in English | MEDLINE | ID: covidwho-992137

ABSTRACT

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.


Subject(s)
Coronavirus Infections , Creatine Kinase, MB Form/blood , Heart Diseases , Natriuretic Peptide, Brain/blood , Pandemics , Peptide Fragments/blood , Pneumonia, Viral , Troponin I/blood , Betacoronavirus/isolation & purification , Biomarkers/blood , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Heart Diseases/blood , Heart Diseases/mortality , Heart Diseases/virology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Mortality , Outcome Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2
16.
Respir Res ; 21(1): 327, 2020 Dec 10.
Article in English | MEDLINE | ID: covidwho-969948

ABSTRACT

Since the coronavirus disease 2019 (COVID-19) identified in Wuhan, Hubei, China in December 2019, it has been characterized as a pandemic by World Health Organization (WHO). It was reported that asymptomatic persons are potential sources of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present an outbreak among health-care workers incited by a doctor who cared a patient with COVID-19 in a Hospital in Wuhan, Hubei, China, which indicates existence of super-spreader even during incubation period.


Subject(s)
COVID-19/transmission , Carrier State , Infectious Disease Incubation Period , Infectious Disease Transmission, Patient-to-Professional , Inhalation Exposure/adverse effects , Occupational Exposure/adverse effects , SARS-CoV-2/pathogenicity , Aged , COVID-19/diagnosis , COVID-19/virology , China , Female , Humans , Time Factors , Virulence
17.
Theranostics ; 10(26): 12223-12240, 2020.
Article in English | MEDLINE | ID: covidwho-934619

ABSTRACT

Rationale: Many viral infections are known to activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway. However, the role of p38 activation in viral infection and the underlying mechanism remain unclear. The role of virus-hijacked p38 MAPK activation in viral infection was investigated in this study. Methods: The correlation of hepatitis C virus (HCV) infection and p38 activation was studied in patient tissues and primary human hepatocytes (PHHs) by immunohistochemistry and western blotting. Coimmunoprecipitation, GST pulldown and confocal microscopy were used to investigate the interaction of p38α and the HCV core protein. In vitro kinase assays and mass spectrometry were used to analyze the phosphorylation of the HCV core protein. Plaque assays, quantitative real time PCR (qRT-PCR), western blotting, siRNA and CRISPR/Cas9 were used to determine the effect of p38 activation on viral replication. Results: HCV infection was associated with p38 activation in clinical samples. HCV infection increased p38 phosphorylation by triggering the interaction of p38α and TGF-ß activated kinase 1 (MAP3K7) binding protein 1 (TAB1). TAB1-mediated p38α activation facilitated HCV replication, and pharmaceutical inhibition of p38α activation by SB203580 suppressed HCV infection at the viral assembly step. Activated p38α interacted with the N-terminal region of the HCV core protein and subsequently phosphorylated the HCV core protein, which promoted HCV core protein oligomerization, an essential step for viral assembly. As expected, SB203580 or the HCV core protein N-terminal peptide (CN-peptide) disrupted the p38α-HCV core protein interaction, efficiently impaired HCV assembly and impeded normal HCV replication in both cultured cells and primary human hepatocytes. Similarly, severe fever with thrombocytopenia syndrome virus (SFTSV), herpes simplex virus type 1 (HSV-1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection also activated p38 MAPK. Most importantly, pharmacological blockage of p38 activation by SB203580 effectively inhibited SFTSV, HSV-1 and SARS-CoV-2. Conclusion: Our study shows that virus-hijacked p38 activation is a key event for viral replication and that pharmacological blockage of p38 activation is an antiviral strategy.


Subject(s)
COVID-19/metabolism , Hepacivirus/metabolism , Hepatitis C/metabolism , Mitogen-Activated Protein Kinase 14/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Adaptor Proteins, Signal Transducing/metabolism , Animals , COVID-19/virology , Chlorocebus aethiops , Enzyme Activation , HEK293 Cells , Hepatitis C/pathology , Hepatitis C/virology , Hepatocytes/metabolism , Humans , Imidazoles/pharmacology , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 14/antagonists & inhibitors , Phosphorylation , Pyridines/pharmacology , Vero Cells , Viral Core Proteins/metabolism , Virus Replication/drug effects
18.
Clin Microbiol Infect ; 27(2): 253-257, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-838644

ABSTRACT

OBJECTIVES: The outbreak of the 2019 coronavirus disease (COVID-19) pandemic in Wuhan, China, has subsided after being hard hit by the disease and subsequent city lockdown. Information on the number of people involved in Wuhan is still inadequate. This study aimed to describe the screening results of 61 437 community members in Wuchang District, Wuhan. METHODS: In mid-May 2020, Wuhan launched a population-scale city-wide SARS-CoV-2 testing campaign, which aimed to perform nucleic acid and viral antibody testing for citizens in Wuhan. Here we show the screening results of cluster sampling of 61 437 residents in Wuchang District, Wuhan, China. RESULTS: A total of 1470 (2.39%, 95% CI 2.27-2.52) individuals were detected positive for at least one antiviral antibody. Among the positive individuals, 324 (0.53%, 95% CI 0.47-0.59) and 1200 (1.95%, 95% CI 1.85-2.07) were positive for immunoglobulin IgM and IgG, respectively, and 54 (0.08%, 95% CI 0.07-0.12) were positive for both antibodies. The positive rate of female carriers of antibodies was higher than those of male counterparts (male-to-female ratio of 0.75), especially in elderly citizens (ratio of 0.18 in 90+ age subgroup), indicating a sexual discrepancy in seroprevalence. In addition, viral nucleic acid detection using real-time PCR had showed 8 (0.013%, 95% CI 0.006-0.026) asymptomatic virus carriers. DISCUSSION: The seroprevalence of SARS-CoV-2 in Wuhan was low. Most Wuhan residents are still susceptible to this virus. Precautions, such as wearing mask, frequent hand hygiene and proper social distance, are necessary before an effective vaccine or antiviral treatments are available.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , Mass Screening/statistics & numerical data , SARS-CoV-2/immunology , Age Distribution , Asymptomatic Infections/epidemiology , COVID-19/blood , COVID-19/virology , COVID-19 Testing , China/epidemiology , Cities/epidemiology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
19.
Med (N Y) ; 2(1): 38-48.e2, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-813759

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. Methods: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. Findings: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. Conclusions: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. Funding: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

20.
Preprint | SSRN | ID: ppcovidwho-1431

ABSTRACT

Background: Corona Virus Disease 2019 (COVID-19) has now become a global pandemic. This necessitated the rapid construction of field hospitals and negative pres

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