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.

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.

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.

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.

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.

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.

Clinical characteristics and the risk factors for severe events of elderly coronavirus disease 2019 patients. / 2019å† çŠ¶ç— æ¯’ç— è€å¹´æ‚£è€ çš„ä¸´åºŠç‰¹ç‚¹åŠé‡ç—‡çš„å±é™©å› ç´ .

OBJECTIVES: To investigate the clinical characteristics and risk factors for severe events of coronavirus disease 2019 (COVID-19) in elderly patients. METHODS: Retrospective analysis was performed on the clinical data of all elderly COVID- 19 patients treated in Changsha Public Health Treatment Center from January 17, 2020 to March 15, 2020, which included basic diseases, symptoms, test results, and other clinical characteristics, and prognostic indicators such as severity of illness, length of hospital stay, virus shedding time and mortality rate. The differences in clinical characteristics and prognostic indicators between elderly, middle-aged, and young COVID-19 patients were also analyzed. Logistic regression model was used to conduct univariate and multivariate analysis of risk factors for developing severe events in elderly COVID-19 patients; receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction efficacy. RESULTS: Of the 230 COVID-19 adult patients, 34 were young patients (14.8%), 136 were middle-aged patients (59.1%), and 60 were elderly (26.1%). Among the 60 elderly patients, 23 were male (38.3%) and 37 were female (61.7%), with a medium age of 66 years old. Common symptoms were fever (66.7%), cough (50.0%), and fatigue (41.7%). C reactive protein (CRP) was increased significantly. The proportion of severe cases was 31.7%, and mortality was 1.7%. The median length of hospitalization and median virus shedding time were 18.5 days and 21 days, respectively. Compared with the young and the middle-aged patients, the elderly had a higher proportion of hypertension, diabetes, and cardiovascular diseases, more common shortness of breath, higher proportions of pneumonia and severe cases (all P<0.05), and the decreased lymphocyte count and lymphocyte percentage (both P<0.05), as well as higher CRP and erythrocyte sedimentation rate (ESR) levels (both P<0.05). Compared with non-severe cases, severe elderly patients demonstrated higher CRP and aspartate aminotransferase (AST) levels (all P<0.05), the reduced lymphocyte count (P<0.05), and the prolonged length of hospitalization and virus shedding duration (both P<0.05). Univariate logistic regression analysis indicated that the lymphocytes proportion, CRP and AST levels were significantly correlated with the risk for developing severe events in elderly COVID-19 patients (all P<0.05). Multivariate logistic regression found that severe events in elderly patients with COVID-19 were significantly correlated with CRP level (OR=1.041, P=0.013). ROC curve analysis revealed that the area under the curve (AUC) for CRP to diagnose severe events in elderly COVID 19 patients was 0.851. CONCLUSIONS: The proportion of severe cases in elderly COVID-19 patients is higher than that in young and middle-aged patients. CRP level has a good predictive value for the possibility of severe events in elderly COVID-19 patients.

Clinical Characteristics of Adult Fevered COVID-19 Patients and Predictors for Developing Severe Events.

Aim: Clinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients did not show fever. However, the difference between the clinical characteristics of fevered and non-fevered patients is still unclear. The aim of the present study was to describe the clinical characteristics of these patients and analyze the predictors for severe events of adult fevered COVID-19 patients. Methods: Clinical and laboratory data of fevered and non-fevered COVID-19 patients in Changsha, China, were collected and analyzed. Logistic regression analysis and Receiver Operating Characteristic Curve (ROC Curve) analysis were adopted to analyze risk factors and evaluate the effectiveness of the predictors for severe events in adult fevered COVID-19 patients. Results: Of the 230 adult COVD-19 patients in this study, 175 patients (76.1%) had fever and 55 patients (23.9%) did not have fever. Compared with non-fevered patients, the fevered patients showed a lower lymphocyte proportion (P = 0.000) and lymphocyte count (P = 0.000) as well as higher levels of C-reactive protein (CRP) (P = 0.000) and erythrocyte sedimentation rate (P = 0.000). The proportion of severe cases was significantly elevated in adult fevered patients (P = 0.000). Compared to non-severe fevered patients, severe fevered patients showed a lower lymphocyte count (P = 0.000), a lower lymphocyte proportion (P = 0.000), and higher levels of CRP (P = 0.000). As determined by the multivariate analysis, CRP (OR 1.026, P = 0.018) and lymphocyte proportion (OR 0.924, P = 0.009) were significantly associated with the risk of developing severe events in fevered adult COVID-19 patients. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for CRP combined with lymphocyte proportion to diagnose severe events in fevered adult COVID-19 patients was 0.874 (95% CI 0.820-0.927). Conclusions: Adult fevered COVID-19 patients were more likely to progress into severe cases, while CRP and lymphocyte proportion were effective predictors for developing severe events in these patients.

C-Reactive Protein Level May Predict the Risk of COVID-19 Aggravation.

BACKGROUND: Clinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study aimed to describe the clinical characteristics of these patients, analyze related factors, and explore predictive markers of the disease aggravation. METHODS: Clinical and laboratory data of nonsevere adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. The receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP). RESULTS: About 7.7% (16/209) of nonsevere adult COVID-19 patients progressed to severe cases after admission. Compared with nonsevere patients, the aggravated patients had much higher levels of CRP (median [range], 43.8 [12.3-101.9] mg/L vs 12.1 [0.1-91.4] mg/L; P = .000). A regression analysis showed that CRP was significantly associated with aggravation of nonsevere COVID-19 patients, with an area under the curve of 0.844 (95% confidence interval, 0.761-0.926) and an optimal threshold value of 26.9 mg/L. CONCLUSIONS: CRP could be a valuable marker to anticipate the possibility of aggravation of nonsevere adult COVID-19 patients, with an optimal threshold value of 26.9 mg/L.