ZBP1 and heatstroke.

Heatstroke, which is associated with circulatory failure and multiple organ dysfunction, is a heat stress-induced life-threatening condition characterized by a raised core body temperature and central nervous system dysfunction. As global warming continues to worsen, heatstroke is expected to become the leading cause of death globally. Despite the severity of this condition, the detailed mechanisms that underlie the pathogenesis of heatstroke still remain largely unknown. Z-DNA-binding protein 1 (ZBP1), also referred to as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1, was initially identified as a tumor-associated and interferon (IFN)-inducible protein, but has recently been reported to be a Z-nucleic acid sensor that regulates cell death and inflammation; however, its biological function is not yet fully understood. In the present study, a brief review of the main regulators is presented, in which the Z-nucleic acid sensor ZBP1 was identified to be a significant factor in regulating the pathological characteristics of heatstroke through ZBP1-dependent signaling. Thus, the lethal mechanism of heatstroke is revealed, in addition to a second function of ZBP1 other than as a nucleic acid sensor.

Pulmonary fibrosis in patients with COVID-19: A retrospective study.

Background: Coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 6 million people worldwide. Although the mortality rate of COVID-19 is very low, many survivors may have different degrees and various sequelae. Previous studies have shown that pulmonary fibrosis (PF) were common on discharged COVID-19 patients, and PF itself is a poor prognostic factor. Methods: 227 COVID-19 hospitalized patients' clinical and laboratory data from the first 15 days following admission were collected in this retrospective study. Groups were based on with or without PF of COVID-19. Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between PF with clinic parameters of multiple time points. Univariate and multivariate logistic regression were used to analyze for risk factors of COVID-19 patients with pulmonary fibrosis. Results: Sixty cases of COVID-19 patients were diagnosed with PF. Compared with 167 non-PF patients, those with PF were older and had higher proportions of fever, shortness of breath, hemoptysis, abdominal pain, hypertension, cardiovascular, diabetes, high flow nasal cannula (HFNC), severe disease, and virus shedding duration. Furthermore, the correlation analysis between PF and clinic parameters showed that PF were positively related to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and negatively correlated with hemoglobin (HGB) and albumin (ALB) at all time points in the first 15 days after admission. Moreover, We found that PF were significantly correlated with coagulation indexes prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and fibrinolysis index D-Dimer at some phases. In addition, Univariate logistic regression analyses showed that age, fever, shortness of breath, hemoptysis, hypertension, cardiovascular, diabetes, HFNC, severe disease were the risk factors of COVID-19 patients with PF. However, multivariate logistic regression showed that age was the risk factor of COVID-19 patients with PF. Conclusion: Combining various factors, advanced age is an independent risk factor of COVID-19 patients with PF. PF was significantly related with clinic parameter of inflammation/coagulopathy/fibrinolysis.

Performance of D-dimer to lymphocyte ratio in predicting the mortality of COVID-19 patients.

Background: Nowadays, there is still no effective treatment developed for COVID-19, and early identification and supportive therapies are essential in reducing the morbidity and mortality of COVID-19. This is the first study to evaluate D-dimer to lymphocyte ratio (DLR) as a prognostic utility in patients with COVID-19. Methods: We retrospectively analyzed 611 patients and separated them into groups of survivors and non-survivors. The area under the curve (AUC) of various predictors integrated into the prognosis of COVID-19 was compared using the receiver operating characteristic (ROC) curve. In order to ascertain the interaction between DLR and survival in COVID-19 patients, the Kaplan-Meier (KM) curve was chosen. Results: Age (OR = 1.053; 95% CI, 1.022-1.086; P = 0.001), NLR (OR = 1.045; 95% CI, 1.001-1.091; P = 0.046), CRP (OR = 1.010; 95% CI, 1.005-1.016; P < 0.001), PT (OR = 1.184; 95% CI, 1.018-1.377; P = 0.029), and DLR (OR = 1.048; 95% CI, 1.018-1.078; P = 0.001) were the independent risk factors related with the mortality of COVID-19. DLR had the highest predictive value for COVID-19 mortality with the AUC of 0.924. Patients' survival was lower when compared to those with lower DLR (Log Rank P <0.001). Conclusion: DLR might indicate a risk factor in the mortality of patients with COVID-19.

The Association Between Alveolar-Arterial Oxygen Tension Difference and the Severity of COVID-19 in Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) emerged as a global pandemic and resulted in a significantly high death toll. Therefore, there is an urgent need to find a potential biomarker related to the disease severity that can facilitate early-stage intervention. METHODS: In the present study, we collected 242 laboratory-confirmed COVID-19-infected patients. The patients were grouped according to the alveolar to arterial oxygen tension difference (PA-aO2) value of COVID-19 infection after admission. RESULTS: Among the 242 laboratory-confirmed COVID-19- infected patients, 155 (64.05%) had an abnormal PA-aO2 value on admission. Compared with the normal PA-aO2 group, the median age of the abnormal PA-aO2 group was significantly older (p = 0.032). Symptoms such as fever, cough, and shortness of breath were more obvious in the abnormal PA-aO2 group. The proportion of severe events in the abnormal PA-aO2 group was higher than the normal PA-aO2 group (10.34% vs. 23.23%, p = 0.013). The abnormal PA-aO2 group had a higher possibility of developing severe events compared with the normal PA-aO2 group (HR 2.622, 95% CI 1.197-5.744, p = 0.016). After adjusting for age and common comorbidities (hypertension and cardiovascular disease), the abnormal PA-aO2 group still exhibited significantly elevated risks of developing severe events than the normal PA-aO2 group (HR 2.986, 95% CI 1.220-7.309, p = 0.017). Additionally, the abnormal PA-aO2 group had more serious inflammation/coagulopathy/fibrinolysis parameters than the normal PA-aO2 group. CONCLUSION: Abnormal PA-aO2 value was found to be common in COVID-19 patients, was strongly related to severe event development, and could be a potential biomarker for the prognosis of COVID-19 patients.

Pulmonary fibrosis in patients with COVID-19: A retrospective study

Background Coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 6 million people worldwide. Although the mortality rate of COVID-19 is very low, many survivors may have different degrees and various sequelae. Previous studies have shown that pulmonary fibrosis (PF) were common on discharged COVID-19 patients, and PF itself is a poor prognostic factor. Methods 227 COVID-19 hospitalized patients' clinical and laboratory data from the first 15 days following admission were collected in this retrospective study. Groups were based on with or without PF of COVID-19. Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between PF with clinic parameters of multiple time points. Univariate and multivariate logistic regression were used to analyze for risk factors of COVID-19 patients with pulmonary fibrosis. Results Sixty cases of COVID-19 patients were diagnosed with PF. Compared with 167 non-PF patients, those with PF were older and had higher proportions of fever, shortness of breath, hemoptysis, abdominal pain, hypertension, cardiovascular, diabetes, high flow nasal cannula (HFNC), severe disease, and virus shedding duration. Furthermore, the correlation analysis between PF and clinic parameters showed that PF were positively related to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and negatively correlated with hemoglobin (HGB) and albumin (ALB) at all time points in the first 15 days after admission. Moreover, We found that PF were significantly correlated with coagulation indexes prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and fibrinolysis index D-Dimer at some phases. In addition, Univariate logistic regression analyses showed that age, fever, shortness of breath, hemoptysis, hypertension, cardiovascular, diabetes, HFNC, severe disease were the risk factors of COVID-19 patients with PF. However, multivariate logistic regression showed that age was the risk factor of COVID-19 patients with PF. Conclusion Combining various factors, advanced age is an independent risk factor of COVID-19 patients with PF. PF was significantly related with clinic parameter of inflammation/coagulopathy/fibrinolysis.

Prevention and treatment of ventilator-associated pneumonia in COVID-19.

Ventilator-associated pneumonia (VAP) is the most common acquired infection in the intensive care unit. Recent studies showed that the critical COVID-19 patients with invasive mechanical ventilation have a high risk of developing VAP, which result in a worse outcome and an increasing economic burden. With the development of critical care medicine, the morbidity and mortality of VAP remains high. Especially since the outbreak of COVID-19, the healthcare system is facing unprecedented challenges. Therefore, many efforts have been made in effective prevention, early diagnosis, and early treatment of VAP. This review focuses on the treatment and prevention drugs of VAP in COVID-19 patients. In general, prevention is more important than treatment for VAP. Prevention of VAP is based on minimizing exposure to mechanical ventilation and encouraging early release. There is little difference in drug prophylaxis from non-COVID-19. In term of treatment of VAP, empirical antibiotics is the main treatment, special attention should be paid to the antimicrobial spectrum and duration of antibiotics because of the existence of drug-resistant bacteria. Further studies with well-designed and large sample size were needed to demonstrate the prevention and treatment of ventilator-associated pneumonia in COVID-19 based on the specificity of COVID-19.

Prevention and treatment of ventilator-associated pneumonia in COVID-19

Ventilator-associated pneumonia (VAP) is the most common acquired infection in the intensive care unit. Recent studies showed that the critical COVID-19 patients with invasive mechanical ventilation have a high risk of developing VAP, which result in a worse outcome and an increasing economic burden. With the development of critical care medicine, the morbidity and mortality of VAP remains high. Especially since the outbreak of COVID-19, the healthcare system is facing unprecedented challenges. Therefore, many efforts have been made in effective prevention, early diagnosis, and early treatment of VAP. This review focuses on the treatment and prevention drugs of VAP in COVID-19 patients. In general, prevention is more important than treatment for VAP. Prevention of VAP is based on minimizing exposure to mechanical ventilation and encouraging early release. There is little difference in drug prophylaxis from non-COVID-19. In term of treatment of VAP, empirical antibiotics is the main treatment, special attention should be paid to the antimicrobial spectrum and duration of antibiotics because of the existence of drug-resistant bacteria. Further studies with well-designed and large sample size were needed to demonstrate the prevention and treatment of ventilator-associated pneumonia in COVID-19 based on the specificity of COVID-19.

The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 5 million people worldwide. It is imperative to identify the disease severity and intervene with effective therapy as early as possible. Previous studies have shown that low free triiodothyronine (FT3) may possess the predictive value on COVID-19 prognosis. Methods: In this retrospective cohort study, 15-day clinical and laboratory data of 186 hospitalized patients of COVID-19 after admission were analyzed. Groups were based on the disease severity of COVID-19, survival or non-survival, and presence or absence of euthyroid sick syndrome (ESS). Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between FT3 with clinic parameters of multiple time points. Results: The non-survival patients had significant lower levels of FT3 (3.24 ± 0.42 vs. 4.19 ± 0.08 pmol/L, p < 0.05) and thyroid-stimulating hormone (TSH) (0.69 ± 0.19 vs. 2.32 ± 0.2 uIU/ml, p < 0.05), and the FT3 of severe patients was significantly lower than that of non-severe patients (3.67 ± 0.14 vs. 4.33 ± 0.09 pmol/L, p < 0.05). Fifty-nine cases of COVID-19 patients were diagnosed with ESS. Compared with non-ESS patients, those with ESS were older and had higher proportions of fever, shortness of breath, hypertension, diabetes, severe disease, and mortality. In addition, the correlation analysis between FT3 and clinical parameters showed that FT3 were positively related to the lymphocyte count and albumin and negatively correlated with C-reactive protein, erythrocyte sedimentation rate, and D-dimer at all time points in the first 15 days after admission. Conclusion: Low FT3 had a significant predictive value on the prognosis of COVID-19 patients, and FT3 was significantly related with clinic parameters of inflammation/coagulopathy/fibrinolysis.

Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19.

BACKGROUND: COVID-19 patients may experience "cytokine storm" when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies. METHODS: This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization. RESULTS: At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients. CONCLUSION: Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.

The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy

Coronavirus disease 2019 (COVID-19) has become a new public health crisis threatening the world. Dysregulated immune responses are the most striking pathophysiological features of patients with severe COVID-19, which can result in multiple-organ failure and death. The cytochrome P450 (CYP) system is the most important drug metabolizing enzyme family, which plays a significant role in the metabolism of endogenous or exogenous substances. Endogenous CYPs participate in the biosynthesis or catabolism of endogenous substances, including steroids, vitamins, eicosanoids, and fatty acids, whilst xenobiotic CYPs are associated with the metabolism of environmental toxins, drugs, and carcinogens. CYP expression and activity are greatly affected by immune response. However, changes in CYP expression and/or function in COVID-19 and their impact on COVID-19 pathophysiology and the metabolism of therapeutic agents in COVID-19, remain unclear. In this analysis, we review current evidence predominantly in the following areas: firstly, the possible changes in CYP expression and/or function in COVID-19;secondly, the effects of CYPs on the metabolism of arachidonic acid, vitamins, and steroid hormones in COVID-19;and thirdly, the effects of CYPs on the metabolism of therapeutic COVID-19 drugs.

Case Report: Next-Generation Sequencing in Diagnosis of Atypical Aspiration Pneumonia.

Since the pandemic of Corona Virus Disease 2019 (COVID-19), especially in the centers most affected, the symptoms such as fever, cough, myalgia or fatigue, and radioactive signs typically related to COVID-19 like ground-glass opacity (GGO) often distract the attention of physicians from other diseases. Aspiration pneumonia and COVID-19 share similarities in some aspects. There may be risk of misdiagnosis in the case of considering radiological patterns of pneumonia. Early diagnosis and treatment often greatly improve prognosis. We herein reported a case of 40-year-old patient who underwent chest CT scan with the discovery of ground-glass opacity, intralobular reticular opacity and interlobular septal thickening, consolidation, and air bronchogram sign, which were mainly located in the middle and upper lobes of the right lung. It was considered to be infection related pneumonia based on the negative reverse transcription-PCR (RT-PCR) result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) was performed and detected nucleic acid sequences of Klebsiella sp. Consequently, the patient accepted sensitive intravenous antibiotics therapy for 13 days and had a remarkable clinical and radiological improvement. His case was followed up through imaging procedures. Because of possible radiologic and clinical similarities between aspiration and COVID-19 pneumonia, COVID-19 can be of some value in proposing a differential diagnosis of aspiration pneumonia. Clinicians could suggest a correct diagnosis by careful examination of the CT images together with attention to the clinical history and judicious utilization of NGS, especially.

Association between non-alcoholic fatty liver disease with the susceptibility and outcome of COVID-19: A retrospective study.

This study aims to evaluate the effect of non-alcoholic fatty liver disease (NAFLD) on the susceptibility and consequences of coronavirus disease 2019 (COVID-19). We retrospectively collected data from 218 adult COVID-19 patients who showed no evidence of excessive alcohol consumption and underwent abdominal ultrasound examinations. Of these patients, 39.4% patients had been diagnosed with NAFLD, which indicates a much higher prevalence of NAFLD than that reported in the general population. Significantly elevated white blood cell count (p = 0.008), alanine aminotransferase (p = 0.000), aspartate aminotransferase (p = 0.006) and C reactive protein (p = 0.012) were found in the patients with NAFLD. These patients also had significantly higher proportions of hypertension (p = 0.006) and diabetes (p = 0.049) than the non-NAFLD cases. No significant differences existed in the severity, mortality, viral shedding time and length of hospital stay between patients with or without NAFLD in the sample population. However, subgroup analyses found that in patients with normal body mass index (BMI), NAFLD sufferers were more likely to experience a severe event (30.0% vs 11.5%, p = 0.021). Kaplan-Meier curve (log-rank p = 0.017) and Cox regression (HR = 3.26, 95% CI: 1.17-9.04, p = 0.023) analyses confirmed that before and after adjusting for gender, age and comorbidities, NAFLD patients with normal BMI had a higher incidence of suffering severe events. People with NAFLD may have a higher proportion of COVID-19. NAFLD may be correlated with the severity of COVID-19 patients in the normal BMI group.

The Role of High-Density Lipoprotein in COVID-19.

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge. Managing a large number of acutely ill patients in a short time, whilst reducing the fatality rate and dealing with complications, brings unique difficulties. The most striking pathophysiological features of patients with severe COVID-19 are dysregulated immune responses and abnormal coagulation function, which can result in multiple-organ failure and death. Normally metabolized high-density lipoprotein (HDL) performs several functions, including reverse cholesterol transport, direct binding to lipopolysaccharide (LPS) to neutralize LPS activity, regulation of inflammatory response, anti-thrombotic effects, antioxidant, and anti-apoptotic properties. Clinical data shows that significantly decreased HDL levels in patients with COVID-19 are correlated with both disease severity and mortality. However, the role of HDL in COVID-19 and its specific mechanism remain unclear. In this analysis, we review current evidence mainly in the following areas: firstly, the pathophysiological characteristics of COVID-19, secondly, the pleiotropic properties of HDL, thirdly, the changes and clinical significance of HDL in COVID-19, and fourthly the prospect of HDL-targeting therapy in COVID-19 to clarify the role of HDL in the pathogenesis of COVID-19 and discuss the potential of HDL therapy in COVID-19.

Case Report: Human Umbilical Cord Mesenchymal Stem Cells as a Therapeutic Intervention for a Critically Ill COVID-19 Patient.

Here we report a critically ill patient who was cured of SARS-CoV-2 infection in Changsha, China. A 66-year-old Chinese woman, with no significant past medical history, developed severe pneumonia-like symptoms and later diagnosed as severe COVID-19 pneumonia. Within 2 months of hospitalization, the patient deteriorated to ARDS including pulmonary edema and SIRS with septic shock. When treatment schemes such as antibiotics plus corticosteroids showed diminished therapeutic value, hUCMSC therapy was compassionately prescribed under the patient's consent of participation. After treatment, there was significant improvement in disease inflammation-related indicators such as IL-4, IL-6, and IL-10. Eventually, it confirmed the therapeutic value that hUCMSCs could dampen the cytokine storm in the critically ill COVID-19 patient and modulated the NK cells. In the continued hUCMSC treatment, gratifying results were achieved in the follow-up of the patient. The data we acquired anticipate a significant therapeutic value of MSC treatment in severe and critically ill patients with COVID-19, while further studies are needed.

Association Between Respiratory Alkalosis and the Prognosis of COVID-19 Patients.

Aim: The aim of the study was to describe the clinical characteristics of patients with or without respiratory alkalosis, and analyze the relationship of respiratory alkalosis and the outcome of adult coronavirus disease 2019 (COVID-19) patients. Methods: Clinical and laboratory data of adult COVID-19 patients in a single center in China, were retrospectively collected and analyzed. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between respiratory alkalosis and prognosis of COVID-19 patients. Results: Of 230 adult COVID-19 patients, 66 patients (28.7%) had respiratory alkalosis on admission. Of 66 patients, the median age was 53 years old (range, 21-84 years), and 43 (65.2%) were female. Compared with those without respiratory alkalosis, patients with respiratory alkalosis were significantly older (P = 0.002), had a higher proportion of female (P = 0.004), and showed higher ratios of underlying diseases including hypertension (P = 0.023) and cardiovascular disease (P = 0.028). Moreover, they demonstrated higher proportion of severe events (P = 0.001). Patients with respiratory alkalosis had a higher possibility of developing severe events compared with those without respiratory alkalosis (Log Rank P = 0.001). After adjusting for gender, age, and comorbidities, patients with respiratory alkalosis still showed significantly elevated risks of developing to severe cases (HR 2.445, 95% CI 1.307-4.571, P = 0.005) using cox regression analyses. Conclusions: Respiratory alkalosis as a common acid-base disorder in COVID-19 patients, was associated with a higher risk of developing severe event.

Smoking Is Correlated With the Prognosis of Coronavirus Disease 2019 (COVID-19) Patients: An Observational Study.

BACKGROUND: Cigarette smoking has been proven to be a risk factor in the development of many diseases. However, it remains controversial with respect to the relationship of smoking with COVID-19. The purpose of this study was to explore the role of smoking in COVID-19. METHODS: A total of 622 patients with COVID-19 in China were enrolled in the study. Corresponding clinical and laboratory data were collected and analyzed. Meanwhile, Kaplan-Meier curve and Cox regression analysis were employed to analyze the association of smoking with survival in patients with COVID-19. RESULTS: Smoking was statistically significant comparing non-survivors and survivors of patients with COVID-19 (P = 0.007). Males had higher proportion of smoking than females (91.9% vs. 8.1%, P < 0.001). Compared with the non-smoker, there was significant statistical difference in the incidence of cerebrovascular disease in smoking patients with COVID-19 (9.7% vs. 3.4%, P = 0.017). White blood cell count (6.3 vs. 5.4; P = 0.037), hemoglobin level (139.0 vs. 127.0; P < 0.001), and creatinine level (77.3 vs. 61.0; P < 0.001) were significantly increased in COVID-19 patients who smoked. Moreover, smoking patients showed a worse survival compared with non-smoking patients (Log Rank P = 0.045). After adjustment for age, gender and underlying diseases, patients with smoking still had higher risk of mortality than that of non-smoking patients (hazard ratio[HR] 1.897, 95% confidence interval [CI]1.058-3.402, P = 0.032). CONCLUSION: Smoking was thought to be a risk factor in predicting the prognosis of COVID-19 and smoking patients might have a higher risk of mortality than that of the non-smoking patients.

Impact of renin-angiotensin system inhibitors use on mortality in severe COVID-19 patients with hypertension: a retrospective observational study.

OBJECTIVE: Association of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) use with coronavirus disease 2019 (COVID-19) remains controversial. We aimed to investigate the impact of ACEI/ARB use on all-cause mortality in severe COVID-19 patients with hypertension. METHODS: We enrolled 650 COVID-19 patients from Changsha and Wuhan city between 17 January 2020 and 8 March 2020. Demographic, clinical characteristics, and outcomes were collected. Multivariable analysis and propensity-score matching were performed to assess the impact of ACEI/ARB therapy on mortality. RESULTS: Among the 650 patients, 126 who had severe COVID-19 concomitant with hypertension were analyzed. The average age was 66 years and 56 (44.4%) were men. There were 37 ACEI/ARB users and 21 in-hospital deaths (mortality rate, 16.7%). Male sex (odds ratio [OR], 5.13; 95% confidence interval [CI], 1.75 to 17.8), but not ACEI/ARB use (OR, 1.09; 95%CI, 0.31 to 3.43), was an independent risk factor for mortality in severe COVID-19 patients with hypertension. After propensity-score matching, 60 severe COVID-19 patients were included and no significant correlation between use of ACEI/ARB and mortality was observed. CONCLUSIONS: There was no significant association of ACEI/ARB use with mortality in severe COVID-19 patients with hypertension. These findings support the continuation of ACEI/ARB therapy for such patients.

Euthyroid Sick Syndrome in Patients With COVID-19.

Background: Coronavirus disease 2019 (COVID-19) has been shown to affect almost every organ throughout the body. However, it is not clear whether the thyroid gland is impaired in COVID-19 patients. Euthyroid sick syndrome (ESS) is usually associated with the disease severity and deterioration prognosis in critical illness. In this study, the thyroid function of COVID-19 patients was assessed and factors associated with outcomes were analyzed to determine the potential predictive value of ESS. Methods: Clinical and laboratory data of COVID-19 patients with or without ESS in Changsha, China, were collected and analyzed on admission. Kaplan-Meier curve and cox regression model were utilized to determine the correlation between ESS and the endpoints. Subsequently, a receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performances of FT3 and C-reactive protein (CRP) in the disease severity. Results: Forty-one (27.52%) cases of COVID-19 patients diagnosed with ESS. ESS patients had higher proportions of fever, shortness of breath, hypertension, diabetes, and severe events than those of non-ESS patients. The levels of erythrocyte sedimentation rate and C-reactive protein, and the positive rate of procalcitonin were significantly higher, whereas the lymphocyte count was apparently lower in ESS patients than in non-ESS patients. The regression analysis showed that ESS was significantly associated with the disease severity of COVID-19 (HR = 2.515, 95% CI: 1.050-6.026, P = 0.039). The areas under the curve (AUCs) for predicting the severe disease were [0.809 (95% CI 0.727-0.892), P < 0.001] and [0.792 (95% CI 0.689-0.895), P < 0.001] for FT3 and CRP, respectively. Conclusion: ESS was significantly associated with the disease severity and inflammatory parameters in COVID-19 patients.

Low high-density lipoprotein level is correlated with the severity of COVID-19 patients: an observational study.

BACKGROUND: The purpose of the study is to describe the blood lipid levels of patients diagnosed with coronavirus disease 2019 (COVID-19) and to analyze the correlation between blood lipid levels and the prognosis of COVID-19 patients. METHODS: In the clinical retrospective analysis, a total of 228 adults infected with COVID-19 were enrolled between January 17, 2020 and March 14, 2020, in Changsha, China. One thousand one hundred and forty healthy participants with matched age and gender were used as control. Median with interquartile range and Mann-Whitney test were adopted to describe and analyze clinical data. The Kaplan-Meier (KM) curve and Cox regression analysis were used to analyze the correlation between high-density lipoprotein cholesterol (HDL-C) and the severity of COVID-19. RESULTS: Compared with control, COVID-19 patients showed significantly lower levels of total cholesterol (TC) [median, 3.76 vs 4.65 mmol/L, P = 0.031], triglyceride [median, 1.08 vs 1.21 mmol/L, P <  0.001], low-density lipoprotein cholesterol (LDL-C) [median, 2.63 vs 2.83 mmol/L, P <  0.001], and HDL-C [median, 0.78 vs 1.37 mmol/L, P <  0.001], while compared with non-severe patients, severe COVID-19 patients only presented lower levels of HDL-C [median, 0.69 vs 0.79 mmol/L, P = 0.032]. In comparison with patients with high HDL-C, patients with low HDL-C showed a higher proportion of male (69.57% vs 45.60%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P <  0.001) and higher proportion of severe events (36.96% vs 14.84%, P = 0.001). Moreover, patients with low HDL-C at admission showed a higher risk of developing severe events compared with those with high HDL-C (Log Rank P = 0.009). After adjusting for age, gender and underlying diseases, they still had elevated possibility of developing severe cases than those with high HDL-C (HR 2.827, 95% CI 1.190-6.714, P = 0.019). CONCLUSIONS: HDL-C level was lower in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.