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

Author

Liu, Hui, Chen, Jing, Yang, Qin, Lei, Fang, Zhang, Changjiang, Qin, Juan-Juan, Chen, Ze, Zhu, Lihua, Song, Xiaohui, Bai, Liangjie, Huang, Xuewei, Liu, Weifang, Zhou, Feng, Chen, Ming-Ming, Zhao, Yan-Ci, Zhang, Xiao-Jing, She, Zhi-Gang, Xu, Qingbo, Ma, Xinliang, Zhang, Peng, Ji, Yan-Xiao, Zhang, Xin, Yang, Juan, Xie, Jing, Ye, Ping, Azzolini, Elena, Aghemo, Alessio, Ciccarelli, Michele, Condorelli, Gianluigi, Stefanini, Giulio G, Xia, Jiahong, Zhang, Bing-Hong, Yuan, Yufeng, Wei, Xiang, Wang, Yibin, Cai, Jingjing, and Li, Hongliang

Subjects
Prevention, Clinical Research, Good Health and Well Being, Blood Cell Count, COVID-19, Hospital Mortality, Humans, Prognosis, Retrospective Studies, Risk Factors, SARS-CoV-2, complete blood count, latent markov model, mortality, prediction model, risk score
Abstract

BackgroundTo develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC).MethodsWe 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).FindingsFive 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.ConclusionsThe 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.FundingThis 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).

Published
2021

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

Author

Cai, Jingjing, Li, Haomiao, Zhang, Changjiang, Chen, Ze, Liu, Hui, Lei, Fang, Qin, Juan-Juan, Liu, Ye-Mao, Zhou, Feng, Song, Xiaohui, Zhou, Jianghua, Zhao, Yan-Ci, Wu, Bin, He, Meiling, Yang, Huilin, Zhu, Lihua, Zhang, Peng, Ji, Yan-Xiao, Zhao, Guang-Nian, Lu, Zhigang, Liu, Liming, Mao, Weiming, Liao, Xiaofeng, Lu, Haofeng, Wang, Daihong, Xia, Xigang, Huang, Xiaodong, Wei, Xiang, Xia, Jiahong, Zhang, Bing-Hong, Yuan, Yufeng, She, Zhi-Gang, Xu, Qingbo, Ma, Xinliang, Wang, Yibin, Yang, Juan, Zhang, Xin, Zhang, Xiao-Jing, and Li, Hongliang

Subjects
Patient Safety, Diabetes, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Good Health and Well Being, Adrenal Cortex Hormones, Area Under Curve, COVID-19, Diabetes Mellitus, Type 2, Humans, Hyperglycemia, Length of Stay, Lymphocytes, Neutrophils, Proportional Hazards Models, ROC Curve, Risk Factors, SARS-CoV-2, Severity of Illness Index, Survival Rate, Treatment Outcome, COVID-19 Drug Treatment, corticosteroids, inflammatory status, mortality, neutrophil-to-lymphocyte ratio, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism
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.

Published
2021

22. Redefining cardiac biomarkers in predicting mortality of inpatients with COVID-19

Author

Qin, Juan-Juan, Cheng, Xu, Zhou, Feng, Lei, Fang, Akolkar, Gauri, Cai, Jingjing, Zhang, Xiao-Jing, Blet, Alice, Xie, Jing, Zhang, Peng, Liu, Ye-Mao, Huang, Zizhen, Zhao, Ling-Ping, Lin, Lijin, Xia, Meng, Chen, Ming-Ming, Song, Xiaohui, Bai, Liangjie, Chen, Ze, Zhang, Xingyuan, Xiang, Da, Chen, Jing, Xu, Qingbo, Ma, Xin-Liang, Touyz, Rhian M, Gao, Chen, Wang, Haitao, Liu, Liming, Mao, Weiming, Luo, Pengcheng, Yan, Youqin, Ye, Ping, Chen, Manhua, Chen, Guohua, Zhu, Lihua, She, Zhi-Gang, Huang, Xiaodong, Yuan, Yufeng, Zhang, Bing-Hong, Wang, Yibin, Liu, Peter P, and Li, Hongliang

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Clinical Research, Cardiovascular, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Betacoronavirus, Biomarkers, COVID-19, China, Coronavirus Infections, Creatine Kinase, MB Form, Female, Heart Diseases, Hospitalization, Humans, Male, Middle Aged, Mortality, Natriuretic Peptide, Brain, Outcome Assessment, Health Care, Pandemics, Peptide Fragments, Pneumonia, Viral, Predictive Value of Tests, Prognosis, Retrospective Studies, SARS-CoV-2, Troponin I, biomarkers, heart diseases, heart injuries, mortality, prognosis, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
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

Published
2020

23. Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes

Author

Cheng, Xu, Liu, Ye-Mao, Li, Haomiao, Zhang, Xin, Lei, Fang, Qin, Juan-Juan, Chen, Ze, Deng, Ke-Qiong, Lin, Lijin, Chen, Ming-Ming, Song, Xiaohui, Xia, Meng, Huang, Xuewei, Liu, Weifang, Cai, Jingjing, Zhang, Xiao-Jing, Zhou, Feng, Zhang, Peng, Wang, Yibin, Ma, Xinliang, Xu, Qingbo, Yang, Juan, Ye, Ping, Mao, Weiming, Huang, Xiaodong, Xia, Jiahong, Zhang, Bing-Hong, Guo, Jiao, Zhu, Lihua, Lu, Zhibing, Yuan, Yufeng, Wei, Xiang, She, Zhi-Gang, Ji, Yan-Xiao, and Li, Hongliang

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Good Health and Well Being, Acidosis, Acidosis, Lactic, Aged, COVID-19, China, Coronavirus Infections, Diabetes Mellitus, Type 2, Female, Hospitalization, Humans, Kidney, Male, Metformin, Middle Aged, Pandemics, Pneumonia, Viral, Retrospective Studies, acidosis, coronavirus disease 2019, inflammation, metformin, mortality, treatment, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.

Published
2020

24. In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

Author

Zhang, Xiao-Jing, Qin, Juan-Juan, Cheng, Xu, Shen, Lijun, Zhao, Yan-Ci, Yuan, Yufeng, Lei, Fang, Chen, Ming-Ming, Yang, Huilin, Bai, Liangjie, Song, Xiaohui, Lin, Lijin, Xia, Meng, Zhou, Feng, Zhou, Jianghua, She, Zhi-Gang, Zhu, Lihua, Ma, Xinliang, Xu, Qingbo, Ye, Ping, Chen, Guohua, Liu, Liming, Mao, Weiming, Yan, Youqin, Xiao, Bing, Lu, Zhigang, Peng, Gang, Liu, Mingyu, Yang, Jun, Yang, Luyu, Zhang, Changjiang, Lu, Haofeng, Xia, Xigang, Wang, Daihong, Liao, Xiaofeng, Wei, Xiang, Zhang, Bing-Hong, Zhang, Xin, Yang, Juan, Zhao, Guang-Nian, Zhang, Peng, Liu, Peter P, Loomba, Rohit, Ji, Yan-Xiao, Xia, Jiahong, Wang, Yibin, Cai, Jingjing, Guo, Jiao, and Li, Hongliang

Subjects
Patient Safety, Prevention, Infectious Diseases, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Angiotensin-Converting Enzyme 2, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Betacoronavirus, COVID-19, Comorbidity, Coronavirus Infections, Cytokine Release Syndrome, Drug Repositioning, Drug Therapy, Combination, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Male, Middle Aged, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Retrospective Studies, SARS-CoV-2, ACEi/ARB, SARS-COV-2, mortality, statin, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism
Abstract

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.

Published
2020

25. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19

Author

Zhang, Peng, Zhu, Lihua, Cai, Jingjing, Lei, Fang, Qin, Juan-Juan, Xie, Jing, Liu, Ye-Mao, Zhao, Yan-Ci, Huang, Xuewei, Lin, Lijin, Xia, Meng, Chen, Ming-Ming, Cheng, Xu, Zhang, Xiao, Guo, Deliang, Peng, Yuanyuan, Ji, Yan-Xiao, Chen, Jing, She, Zhi-Gang, Wang, Yibin, Xu, Qingbo, Tan, Renfu, Wang, Haitao, Lin, Jun, Luo, Pengcheng, Fu, Shouzhi, Cai, Hongbin, Ye, Ping, Xiao, Bing, Mao, Weiming, Liu, Liming, Yan, Youqin, Liu, Mingyu, Chen, Manhua, Zhang, Xiao-Jing, Wang, Xinghuan, Touyz, Rhian M, Xia, Jiahong, Zhang, Bing-Hong, Huang, Xiaodong, Yuan, Yufeng, Loomba, Rohit, Liu, Peter P, and Li, Hongliang

Subjects
Cardiovascular, Clinical Research, Hypertension, Good Health and Well Being, Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, COVID-19, Coronavirus Infections, Female, Hospital Mortality, Humans, Inpatients, Male, Middle Aged, Pandemics, Pneumonia, Viral, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, coronavirus, hypertension, inpatients, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

RationaleUse of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.ObjectiveTo determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.Methods and resultsThis retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.ConclusionsAmong hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Published
2020

44. Resident stem cells in the heart

Author

Gong Hui, Wang Ting, and Xu Qingbo

Subjects
adult heart, ischemic heart disease, resident stem/progenitor cells, Medicine
Abstract

Cardiovascular disease is the leading cause of mobility and morality worldwide, in which the ischemic heart disease is the most common type of the diseases. During last decade, a major progress in the study of the pathogenesis of heart disease has been achieved. For example, the discovery of adult stem/progenitor cells in the heart and vessel tissues may play a role in tissue regeneration. However, the issue of 31 retractions for cardiac stem cell work has caused a “storm of trust” in the heart stem cell field, in which both founders and scientists have become cautious and conservative in stem cell research of the heart. Despite that the existence of adult cardiac stem cells has been denied, recent studies confirmed that there are many other resident stem/progenitor cells in adult heart. Although these cells cannot differentiate into cardiomyocytes, the role they played in heart repair after injury should not be ignored. The purpose of this short article is to briefly review the current research progress in resident stem/progenitor cells in the heart, to discuss how they function during cardiac repair and to point out unanswered questions in the research field.

Published
2021
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46. Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species

Author

Zhang, Xiao-Jing, Liu, Xiaolan, Hu, Manli, Zhao, Guo-Jun, Sun, Dating, Cheng, Xu, Xiang, Hui, Huang, Yong-Ping, Tian, Rui-Feng, Shen, Li-Jun, Ma, Jun-Peng, Wang, Hai-Ping, Tian, Song, Gan, Shanyu, Xu, Haibo, Liao, Rufang, Zou, Toujun, Ji, Yan-Xiao, Zhang, Peng, Cai, Jingjing, Wang, Zhao V., Meng, Guannan, Xu, Qingbo, Wang, Yibin, Ma, Xin-Liang, Liu, Peter P., Huang, Zan, Zhu, Lihua, She, Zhi-Gang, Zhang, Xin, Bai, Lan, Yang, Hailong, Lu, Zhibing, and Li, Hongliang

Published
2021
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