The role of NLRP3 inflammasome in sepsis: A potential therapeutic target.

Sepsis is the host immune imbalance following infection and leads to organ dysfunction, with highly complicated pathophysiology. To date, sepsis still lacks effective therapies with high mortality rates. Recently, numerous studies have highlighted the potential of NLRP3 inflammasome as a therapeutic target during sepsis. NLRP3 inflammasome is a protein complex that could induce the activation of caspase-1 and the following release of pro-inflammatory cytokines such as IL-1ß and IL-18. It was demonstrated that NLRP3 inflammasome was involved in the development and progression of sepsis. In contrast, inhibition of NLRP3 inflammasome activation could mitigate the inflammatory response, protect organ function, and improve outcomes and mortality. This paper illustrated the activation pathways of the NLRP3 inflammasome and its possible molecular mechanisms in the pathophysiology of sepsis. Meanwhile, the beneficial effects of inhibiting NLRP3 activation in sepsis-related organ damage were also presented. In addition, the diverse role of NLRP3 inflammasome in bacterial clearance was addressed. Of note, several herbal extracts targeting NLRP3 inflammasome in the treatment of sepsis were emphasized. We hope that this paper could provide a basis for further drug research targeting NLRP3 inflammasome.

The differences in virus shedding time between the Delta variant and original SARS-CoV-2 infected patients.

Background: The worldwide epidemic of Coronavirus Disease 2019 (COVID-19) has evolved into multiple variants. The Delta variant is known for its ability to spread and replicate, while data are limited about the virus shedding time in patients infected by the Delta variant. Methods: 56 Delta variant and 56 original SARS-CoV-2 infected patients from Hunan, China, matched according to age and gender divided into two groups and compared the baseline characteristics and laboratory findings with appropriate statistical methods. Results: Patients infected with the Delta variant had significantly fewer symptoms of fever (p < 0.001), fatigue (p = 0.004), anorexia (p < 0.001), shortness of breath (p = 0.004), diarrhea (p = 0.006), positive pneumonia rate of chest CT (p = 0.019) and chest CT ground glass opacities (p = 0.004) than those of patients with the original SARS-CoV-2. Patients of the Delta variant group had a significantly longer virus shedding time [41.5 (31.5, 46.75) vs. 18.5 (13, 25.75), p < 0.001] compared with the original SARS-CoV-2 group. The correlation analyses between the virus shedding time and clinical or laboratory parameters showed that the virus shedding time was positively related to the viral strain, serum creatinine and creatine kinase isoenzyme, while negatively correlated with lymphocyte count, total bilirubin and low-density lipoprotein. Finally, the viral strain and lymphocyte count were thought of as the independent risk factors of the virus shedding time demonstrated by multiple linear regression. Conclusion: COVID-19 patients infected with the Delta variant exhibited fewer gastrointestinal symptoms and prolonged virus shedding time than those infected with the original SARS-CoV-2. Delta variant and fewer lymphocyte were correlated with prolonged virus shedding time.

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.

The Potential of NLRP3 Inflammasome as a Therapeutic Target in Neurological Diseases.

NLRP3 (NLRP3: NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is the best-described inflammasome that plays a crucial role in the innate immune system and a wide range of diseases. The intimate association of NLRP3 with neurological disorders, including neurodegenerative diseases and strokes, further emphasizes its prominence as a clinical target for pharmacological intervention. However, after decades of exploration, the mechanism of NLRP3 activation remains indefinite. This review highlights recent advances and gaps in our insights into the regulation of NLRP3 inflammasome. Furthermore, we present several emerging pharmacological approaches of clinical translational potential targeting the NLRP3 inflammasome in neurological diseases. More importantly, despite small-molecule inhibitors of the NLRP3 inflammasome, we have focused explicitly on Chinese herbal medicine and botanical ingredients, which may be splendid therapeutics by inhibiting NLRP3 inflammasome for central nervous system disorders. We expect that we can contribute new perspectives to the treatment of neurological diseases.

Application of oXiris-continuous hemofiltration adsorption in patients with sepsis and septic shock: A single-centre experience in China.

oXiris is a new, high-adsorption membrane filter in continuous hemofiltration adsorption to reduce the inflammatory response in sepsis. The investigators retrospectively reviewed patients with sepsis/septic shock who underwent at least one oXiris-treatment from November 2020 to March 2022. The demographic data, baseline levels before treatment, clinical datas, prognosis, and the occurrence of adverse events during treatment were recorded. 90 patients were enrolled in this study. The hemodynamic indices, sequential organ failure assessment score, lactate, inflammatory biomarkers levels were significantly improved at 12 h and 24 h after treatment. Procalcitonin and interleukin-6 reduction post-treatment of oXiris were most pronounced in infection from skin and soft tissue, urinary and abdominal cavity. Logistic regression analysis showed that pre-treatment sequential organ failure assessment score (p = 0.034), percentage decrease in sequential organ failure assessment score (p = 0.004), and age (p = 0.011) were independent risk factors for intensive care unit mortality. In conclusion, oXiris-continuous hemofiltration adsorption may improve hemodynamic indicators, reduce the use of vasoactive drugs, reduce lactate level and infection indicators. Of note, oXiris improve organ function in sepsis, which may result to higher survival rate.

Case Report: Therapeutic Strategy With Delayed Debridement for Culture-Negative Invasive Group A Streptococcal Infections Diagnosed by Metagenomic Next-Generation Sequencing.

Streptococcal toxic shock syndrome (STSS) caused by group A streptococcus is a rare condition that rapidly developed to multiple organ failure even death. Therefore, prompt diagnosis, initiate appropriate antibiotics and other supportive treatments are critical. Here we reported a case of STSS caused by group A streptococcus infection. A healthy 39-year-old man presented a sudden pain in the left lower extremity, followed by a high fever (40.0 °C) with dizziness, nausea, and shortness of breath. Twenty-four hours before the visit, the patient showed anuria. The patient was then admitted to the intensive care unit. Blood examination revealed elevated levels of inflammatory markers and creatinine. He suffered from septic shock, dysfunction of coagulation, acute kidney dysfunction, acute respiratory distress syndrome, and acute liver function injury. The diagnosis was obtained through clinical manifestation and metagenomic next-generation sequencing (mNGS) drawn from the pustule and deep soft tissue (lower limb) samples while all bacterial cultures came back negative. The pustule mNGS report detected a total of 132 unique group A streptococcus sequence reads, representing 96.3% of microbial reads while the soft tissue mNGS report identified a total of 142474 unique group A streptococcus sequence reads, representing 100% of microbial reads. The patient was treated with aggressive fluid resuscitation, antibiotics comprising piperacillin/tazobactam and clindamycin, respiratory support, following the delayed surgical debridement. Intravenous immunoglobulin was also used for 5 days. On the 14th day after admission, he was transferred to the general ward for follow-up treatment. Our case highlighted, for the first time, the key role of mNGS in the early diagnosis of culture-negative invasive group A streptococcal infection. The case also suggested that clindamycin combined with beta-lactam antibiotics and adjunction of intravenous immunoglobulin therapy with delayed debridement performed well in the management of unstable STSS 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.

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.

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.

Clinical Findings in Diabetes Mellitus Patients with COVID-19.

BACKGROUNDS: Diabetes mellitus (DM) is one of the most common comorbidities in patients with coronavirus disease (COVID-19). We aim to summarize the clinical features of DM patients with COVID-19 and find out potential factors associated with severe disease. METHODS: In this retrospective, single-center study, the medical records of patients with COVID-19 in Changsha, Hunan, China, from January 21, 2020, to February 19, 2020, were reviewed. Epidemiological information, clinical features, and outcomes were compared between DM patients admitted to the intensive care unit (ICU) or not. RESULTS: A total of 241 patients confirmed with COVID-19 were enrolled, including 19 DM patients. There were more patients in DM group admitted to the ICU than non-DM group (36.8% vs. 15.8%, P = 0.045). Compared with non-DM group in the ICU, there were more female patients from DM group in the ICU (85.7% vs. 31.4%, P = 0.024). On admission, the mean level of glycated hemoglobin A1c (HbA1c) was higher in the ICU DM patients than that in the non-ICU DM patients (8.5% vs. 7.1%). There were more DM patients with proteinuria in the ICU group than the non-ICU group (57.1% vs. 33.3%). Twelve DM patients (63.2%) changed diabetic therapy during hospitalization, and all DM patients admitted to the ICU used insulin. As of March 14, all 19 DM patients have been discharged, and no death occurred. CONCLUSIONS: DM patients with COVID-19 are vulnerable to severe disease, especially for female patients. High levels of HbA1c and proteinuria could be potential risk factors for severe COVID-19 in DM patients. In addition to timely systemic therapy, the control of blood glucose and proper diabetic therapy is essential to improve the prognosis of severe DM patients with COVID-19.

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.

Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients.

Ventilator-associated pneumonia (VAP), a hospital acquired pneumonia that occurs more than 48 h after mechanical ventilation, is a common complication of mechanical ventilation with a high mortality rate. VAP can cause patients to have difficulty weaning off the ventilator and to stay in the hospital longer, which results in a huge financial burden to patients and a huge demand for medical resources. Several strategies, such as drugs including chlorhexidine, ß-lactam antibiotics and probiotics, have been used to prevent VAP in clinic. The incidence and the mortality rate of VAP have been decreased with the development of preventative strategies in the past decades, but VAP remains one of the most common causes of nosocomial infections and death in the intensive care unit. Current challenges in the management of VAP involved the lack of a gold standard for diagnosis, the absence of effective preventative strategies, and the rise in antibiotic resistance. Therefore, in order to reduce the incidence of VAP and improve the outcome of patients with mechanical ventilation, it is necessary to clarify the risk factors of VAP for clinical prevention and control of VAP. This paper reviews the international risk factors of VAP occurrence reported in recent years, including patient characteristics, increased mechanical ventilation time and prolonged length of hospital stay, disorders of consciousness, burns, comorbidities, prior antibiotic therapy, invasive operations, gene polymorphisms, and mentions the corresponding preventive measures. Each factor is not only an independent risk factor of VAP, but also has an influence on each other. A better understanding of risk factors for VAP is helpful for predicting the occurrence of VAP, improving the prevention and control of VAP, and reducing the morbidity and mortality rates of patients with VAP.

The Associations between Paraoxonase 1 L55M/Q192R Genetic Polymorphisms and the Susceptibilities of Diabetic Macroangiopathy and Diabetic Microangiopathy: A Meta-Analysis.

INTRODUCTION: Plenty of studies have focused on the associations of paraoxonase 1 Q192R and L55M genetic polymorphisms with diabetic macroangiopathy and microangiopathy susceptibility, but these associations remain controversial. Therefore, this meta-analysis was conducted to demonstrate these relationships. METHODS: Relevant studies published in English or Chinese were identified in PubMed, Embase, Wanfang Database, and CNKI by applying specific inclusion and exclusion criteria. Statistical analyses were performed using the STATA 12.0 statistical software. RESULTS: 25 Case-control studies were included in the meta-analyses: six on the association between paraoxonase 1 L55M genetic polymorphism and diabetic macroangiopathy risk, nine on the association between L55M and diabetic microangiopathy risk, 12 on the association between Q192R and diabetic macroangiopathy risk, and 12 on the association between Q192R and diabetic microangiopathy risk. Paraoxonase 1 L55M genetic polymorphism was significantly associated with diabetic microangiopathy susceptibility in the dominant model [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.33-0.83, P = 0.006], the homozygous model (OR 0.37, 95% CI 0.16-0.86, P = 0.021), the allelic contrast model (OR 0.62, 95% CI 0.43-0.90, P = 0.011), the recessive model (OR 12.04, 95% CI 8.02-18.06, P = 0.000), and the heterozygous model (OR 0.57, 95% CI 0.38-0.85, P = 0.006), but L55M was not significantly associated with macroangiopathy susceptibility. Paraoxonase 1 Q192R genetic polymorphism was significantly associated with diabetic macroangiopathy susceptibility in the homozygous model (OR 1.88, 95% CI 1.06-3.32, P = 0.030), the allelic contrast model (OR 1.31, 95% CI 1.02-1.69, P = 0.038), and the recessive model (OR 1.55, 95% CI 1.11-2.16, P = 0.010), but not in the dominant and heterozygous models. Meanwhile, there was no significant association between paraoxonase 1 Q192R genetic polymorphism and diabetic microangiopathy susceptibility. CONCLUSION: Paraoxonase 1 L55M and Q192R genetic polymorphisms play important roles in diabetic macroangiopathy and microangiopathy susceptibility. Further well-designed studies based on large samples are needed to confirm these results.