Sensitivity Enhanced Plasmonic Biosensor Using Bi2Se3-Graphene Heterostructures: A Theoretical Analysis.

This study provided a theoretical insight for designing novel plasmonic biosensors using bismuth selenide (Bi2Se3)-Graphene heterostructures. It was a van der Waals (vdWs) stacked configuration composed of gold (Au) film, few quintuple layer (QL) Bi2Se3 and few-layered graphene. In particular, the proposed biosensor was created by Goos-Hänchen (GH) shift rather than phase, resulting in a more sensitive biosensing response. Under the excitation of 632.8 nm, significant sensitivity enhancement performance was obtained via varying the thickness of Bi2Se3-Graphene heterostructures. The best configuration was 32 nm Au film-2-QL Bi2Se3-3-layer graphene, generating the largest GH shift, as high as -1.0202 × 104 µm. Moreover, the highest detection sensitivity was determined to be 8.5017 × 106 µm/RIU, responding to a tiny refractive index (RI) change of 0.0012 RIU (RIU, refractive index unit). More importantly, our proposed biosensor has shown a theoretical feasibility of monitoring virus samples. For example, there was an efficient linear detection range for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 0~13.44 nanomole (nM)) and its Spike (S) glycoprotein (0~59.74 nM), respectively. It is expected that our proposed plasmonic biosensor has a potential application in performing sensitive detection of SARS-CoV-2.

Investigation on the effectiveness of ventilation dilution on mitigating COVID-19 patients' secondary airway damage due to exposure to disinfectants.

Chlorine-containing disinfectants are widely used in hospitals to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection. Meanwhile, ventilation is a simple but effective means to maintain clean air. It is essential to explore the exposure level and health effects of coronavirus disease 2019 patients' inhalation exposure to by-products of chloride-containing disinfectants under frequent surface disinfection and understand the role of ventilation in mitigating subsequent airway damage. We determined ventilation dilution performance and indoor air quality of two intensive care unit wards of the largest temporary hospital constructed in China, Leishenshan Hospital. The chloride inhalation exposure levels, and health risks indicated by interleukin-6 and D-dimer test results of 32 patients were analysed. The mean ± standard deviation values of the outdoor air change rate in the two intensive care unit wards were 8.8 ± 1.5 h-1 (Intensive care unit 1) and 4.1 ± 1.4 h-1 (Intensive care unit 2). The median carbon dioxide and fine particulate matter concentrations were 480 ppm and 19 µg/m3 for intensive care unit 1, and 567 ppm and 21 µg/m3 for intensive care unit 2, all of which were around the average levels of those in permanent hospitals (579 ppm and 21 µg/m3). Of these patients, the median (lower quartile, upper quartile) chloride exposure time and calculated dose were 26.66 (2.89, 57.21) h and 0.357 (0.008, 1.317) mg, respectively. A statistically significant positive correlation was observed between interleukin-6 and D-dimer concentrations. To conclude, ventilation helped maintain ward air cleanliness and health risks were not observed.

The health and economic impact of constructing temporary field hospitals to meet the COVID-19 pandemic surge: Wuhan Leishenshan Hospital in China as a case study.

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.

Compared hand hygiene compliance among healthcare providers before and after the COVID-19 pandemic: A rapid review and meta-analysis.

BACKGROUND: Hand hygiene (HH) is a cost-effective measure to reduce health care-associated infections. The overall characteristics and changes of hand hygiene compliance (HHC) among health care 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 health care 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 5-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 2,377 health care 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 5-moments, the health care providers had the highest HHC after contact with the body fluids of the patients (91%; 95% CI:88%-94%), while before contact with patient's health care 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% versus openly and secretly observation: 91%; 95% CI: 90%-91%). CONCLUSIONS: During the COVID-19 pandemic, the compliance of health care 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.

Newly-Diagnosed Diabetes and Sustained Hyperglycemia are Associated with Poorer Outcomes in COVID-19 Inpatients Without Pre-Existing Diabetes.

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.

Risk factors for COVID-19 progression and mortality in hospitalized patients without pre-existing comorbidities.

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.

Clinical Characteristics of Cancer Patients With COVID-19: A Retrospective Multicentric Study in 19 Hospitals Within Hubei, China.

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.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma.

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.

Cardiac Involvement in Recovered Patients From COVID-19: A Preliminary 6-Month Follow-Up Study.

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.

A risk score based on baseline risk factors for predicting mortality in COVID-19 patients.

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.

Extracorporeal Membrane Oxygenation Therapy for Critically Ill Coronavirus Disease 2019 Patients in Wuhan, China: A Retrospective Multicenter Cohort Study.

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19.

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.

Development and validation of a risk score using complete blood count to predict in-hospital mortality in COVID-19 patients.

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).

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

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.

A super-spreader of SARS-CoV-2 in incubation period among health-care workers.

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.

Virus-induced p38 MAPK activation facilitates viral infection.

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.

Seroprevalence of SARS-CoV-2 immunoglobulin antibodies in Wuhan, China: part of the city-wide massive testing campaign.

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.