The effect of glucocorticoids on mortality in severe COVID-19 patients: Evidence from 13 studies involving 6612 cases

Background:Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for effective therapies for patients with COVID-19. In this study, we aimed to assess the therapeutic efficacy of glucocorticoids in severe COVID-19.Methods:A systematic literature search was performed across PubMed, Web of Science, EMBASE, and the Cochrane Library (up to June 26, 2021). The literature investigated the outcomes of interest were mortality and invasive mechanical ventilation.Results:The search identified 13 studies with 6612 confirmed severe COVID-19 patients. Our meta-analysis found that using glucocorticoids could significantly decrease COVID-19 mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.45–0.79, P < .001), relative to non-use of glucocorticoids. Meanwhile, using glucocorticoids also could significantly decrease the risk of progression to invasive mechanical ventilation for severe COVID-19 patients (HR = 0.69, 95% CI 0.58–0.83, P < .001). Compared with using dexamethasone (HR = 0.68, 95% CI 0.50–0.92, P = .012), methylprednisolone use had a better therapeutic effect for reducing the mortality of patients (HR = 0.35, 95% CI 0.19–0.64, P = .001).Conclusion:The result of this meta-analysis showed that using glucocorticoids could reduce mortality and risk of progression to invasive mechanical ventilation in severe COVID-19 patients.     

Corrected QT interval in hospitalized patients with coronavirus disease 2019: Focus on drugs therapy

Corrected QT (QTc) interval prolongation has been associated with poor patient prognosis. In this study, we assessed the effects of different drugs and cardiac injury on QTc interval prolongation in patients with coronavirus disease 2019 (COVID-19).The study cohort consisted of 395 confirmed COVID-19 cases from the Wuhan Union Hospital West Campus. All hospitalized patients were treated with chloroquine/hydroxychloroquine (CQ/HCQ), lopinavir/ritonavir (LPV/r), quinolones, interferon, Arbidol, or Qingfei Paidu decoction (QPD) and received at least 1 electrocardiogram after drug administration.Fifty one (12.9%) patients exhibited QTc prolongation (QTc ≥ 470 ms). QTc interval prolongation was associated with COVID-19 severity and mortality (both P < .001). Administration of CQ/HCQ (odds ratio [OR], 2.759; 95% confidence interval [CI], 1.318–5.775; P = .007), LPV/r (OR, 2.342; 95% CI, 1.152–4.760; P = .019), and quinolones (OR, 2.268; 95% CI, 1.171–4.392; P = .015) increased the risk of QTc prolongation. In contrast, the administration of Arbidol, interferon, or QPD did not increase the risk of QTc prolongation. Notably, patients treated with QPD had a shorter QTc duration than those without QPD treatment (412.10 [384.39–433.77] vs 420.86 [388.19–459.58]; P = .042). The QTc interval was positively correlated with the levels of cardiac biomarkers (creatine kinase-MB fraction [rho = 0.14, P = .016], high-sensitivity troponin I [rho = .22, P < .001], and B-type natriuretic peptide [rho = 0.27, P < .001]).In conclusion, QTc prolongation was associated with COVID-19 severity and mortality. The risk of QTc prolongation was higher in patients receiving CQ/HCQ, LPV/r, and quinolones. QPD had less significant effects on QTc prolongation than other antiviral agents.     

Postoperative complications observed with robotic versus laparoscopic surgery for the treatment of rectal cancer: An updated meta-analysis of recently published studies

Background:This is an updated meta-analysis comparing the postoperative complications observed with robotic versus laparoscopic surgery (LS) for the treatment of rectal cancer.Methods:Cochrane central, MEDLNE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica dataBASE), Google Scholar, Web of Science and http://www.ClinicalTrials.gov were searched for studies (published after the year 2015), comparing robotic versus LS for the treatment of rectal cancer. The postoperative outcomes were considered as the endpoints in this analysis. RevMan 5.4 was used to carry out the statistical analysis. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the results following data analysis.ResultsA total number of 22,744 participants were included in this study whereby 9178 participants were assigned to the robotic surgery and 13,566 participants were assigned to the LS group. The time period of patients’ enrollment varied from years 2007 to 2017. Our results showed that overall complications (RR: 0.91, 95% CI: 0.71–1.17; P = .45), wound complications (RR: 0.81, 95% CI: 0.64–1.04; P = .09), anastomotic leak (RR: 1.12, 95% CI: 0.88–1.42; P = .37), anastomotic bleeding (RR: 0.88, 95% CI: 0.29–2.64; P = .82), stoma-related complications (RR: 0.88, 95% CI: 0.24–3.21; P = .85), intra-abdominal abscess (RR: 0.53. 95% CI: 0.22–1.31; P = .17), urinary tract infection (RR: 0.94, 95% CI: 0.53–1.66; P = .83), enterocolitis (RR: 1.35, 95% CI: 0.38–4.71; P = .64), reoperation (RR: 0.85, 95% CI: 0.46–1.54; P = .58), and mortality (RR: 0.75, 95% CI: 0.34–1.62; P = .46) were not significantly different between robotic-assisted versus LS for rectal cancer. Postoperative ileus (RR: 1.21, 95% CI: 0.81–1.81; P = .34), readmission (RR: 1.17, 95% CI: 0.75–1.83; P = .48), and urinary retention (RR: 0.51, 95% CI: 0.21–1.23; P = .14) were also similarly manifested.Conclusions:In this updated meta-analysis, both robotic and laparoscopic surgeries were equally effective for the treatment of rectal cancer. Similar postoperative complications were observed. However, our analysis was restricted only to postoperative outcomes, parameters such as duration of surgery were not taken into consideration.     

The effect of coagulation factors in 2019 novel coronavirus patients: A systematic review and meta-analysis

Background:The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19.Methods:We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity.Results:Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization.Conclusion:Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed.Trial registration:PROSPERO (CRD42020183514).     

The safety and efficacy of low-dose mineralocorticoid receptor antagonists in dialysis patients: A meta-analysis

Introduction:Our aim was to evaluate the safety and efficacy of low-dose mineralocorticoid receptor antagonists (MRAs) in dialysis patients.Methods:We systematically searched PubMed, EMBASE, and Cochrane libraries for clinical trials on the use of MRAs in dialysis patients. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence.Results:We identified nine randomized controlled trials including 1128 chronic dialysis patients. In terms of safety, when hyperkalemia was defined as serum potassium level ≥5.5 mmol/L, low-dose MRAs were significantly associated with hyperkalemia (relative risk [RR] 1.76, 95% confidence intervals [CI] 1.07–2.89, P = .02); however, when hyperkalemia was defined as serum potassium level ≥6.0 mmol/L or serum potassium level ≥6.5 mmol/L, no significant association was observed between low-dose MRAs and hyperkalemia (RR 1.40, 95% CI 0.83–2.37, P = .20; RR 1.98, 95% CI 0.91–4.30, P = .09, respectively). Use of low-dose MRAs can reduce cardiovascular mortality by 54% compared with the control group (0.46, 95% CI 0.28–0.76, P = .003). Similarly, the RR of all-cause mortality for the low-dose MRAs group was 0.48 (95% CI 0.33–0.72, P = .0003).Conclusion:Low-dose MRAs may benefit dialysis patients without significantly increasing moderate to severe hyperkalemia.     

The effect of nurse-led interventions on re-admission and mortality for congestive heart failure: A meta-analysis

Background:The European Society of Cardiology guidelines recommend the implementation of nurse-led heart failure programs to achieve optimal management of patients with congestive heart failure (CHF). In this analysis, we aimed to systematically show the impact of nurse-led interventions (NLI) on re-admission and mortality in patients with CHF (reduced ejection fraction).Methods:Publications reporting the impact of NLI on readmission and mortality in patients with CHF were carefully searched from electronic databases. Rehospitalization and mortality were the endpoints. For this analysis, the latest version of the RevMan software was used. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data following analysis.Results:A total number of 3282 participants with CHF were included in this analysis. A total of 1571 patients were assigned to the nurse-led intervention group whereas 1711 patients were assigned to the usual care group. The patients had a mean age ranging from 50.8 to 80.3 years. Male patients varied from 27.3% to 73.8%. Comorbidities including hypertension (24.6%–80.0%) and diabetes mellitus (16.7%–59.7%) were also reported. Patients had a mean left ventricular ejection fraction varying from 29.0% to 61.0%. Results of this current analysis showed that rehospitalization (RR: 0.81, 95% CI: 0.74–0.88; P = .00001) and mortality (RR: 0.69, 95% CI: 0.56–0.86; P = .0009) were significantly lower among CHF patients who were assigned to the nurse-led intervention. Whether during a shorter (3–6 months) or a longer (1–2 years) follow up time period, rehospitalization for shorter [(RR: 0.73, 95% CI: 0.65–0.82; P = .00001) vs for longer (RR: 0.81, 95% CI: 0.72–0.91; P = .0003) respectively] and mortality for shorter [(RR: 0.55, 95% CI: 0.38–0.80; P = .002) vs longer follow up time period (RR: 0.76, 95% CI: 0.58–0.99; P = .04) respectively] were significantly lower and in favor of the nurse-led interventional compared to the normal care group.Conclusions:This systematic review and meta-analysis of randomized controlled trials showed that NLI had significant impacts in reducing the risk of rehospitalization and mortality in these patients with CHF (reduced ejection fraction). Hence, we believe that nurse-led clinics and other interventional programs would be beneficial to patients with heart failure and this practice should, in the future be implemented to the health care system.     

Impacto de los inhibidores de la enzima de conversión de la angiotensina y los antagonistas del receptor de la angiotensina II en la COVID-19 en una población occidental. Registro CARDIOVID

Introduction and objectivesCoronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection.MethodsSingle-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models.ResultsOf the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P = .486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P = .622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P = .638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P = .798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P = .915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization.ConclusionsPrevious treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.     

Sustained low efficiency dialysis is non-inferior to continuous renal replacement therapy in critically ill patients with acute kidney injury: A comparative meta-analysis

Background:Critically ill adults with acute kidney injury (AKI) experience considerable morbidity and mortality. This systematic review aimed to compare the effectiveness of continuous renal replacement therapy (CCRT) versus sustained low efficiency dialysis (SLED) for individuals with AKI.Methods:We carried out a systematic search of existing databases according to standard methods and random effects models were used to generate the overall estimate. Heterogeneity coefficient was also calculated for each outcome measure.Results:Eleven studies having 1160 patients with AKI were included in the analyses. Meta-analysis results indicated that there was no statistically significant difference between SLED versus continuous renal replacement therapy (CRRT) in our primary outcomes, like mortality rate (rate ratio [RR] 0.67, 95% confidence interval [CI] 0.44–1.00; P = .05), renal recovery (RR 1.08, 95% CI 0.83–1.42; P = .56), and dialysis dependence (RR = 1.03, 95% CI 0.69–1.53; P = .89). Also, no statistically significant difference was observed for between SLED versus CRRT in the secondary outcomes: that is, length of intensive care unit stay (mean difference –0.16, 95% CI –0.56–0.22; P = .41) and fluid removal rate (mean difference –0.24, 95% CI –0.72–0.24; P = .32). The summary mean difference indicated that there was a significant difference in the serum phosphate clearance among patients treated with SLED and CRRT (mean difference –1.17, 95% CI –1.90 to –0.44, P = .002).Conclusions:The analysis indicate that there was no major advantage of using continuous renal replacement compared with sustained low efficiency dialysis in hemodynamically unstable AKI patients. Both modalities are equally safe and effective in treating AKI among critically ill patients.     

Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin,a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis

Background:In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI).Methods:Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis.Results:A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84–1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78–1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74–1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53–1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56–2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54–0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64–0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35–0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42–0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13–0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51–0.90; P = .008) were significantly higher with TT.Conclusions:DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.     

Effectiveness of tocilizumab in the treatment of hospitalized adults COVID-19: A systematic review and meta-analysis

Background:Since December 2019, the coronavirus disease (COVID-19) has spread worldwide, leading to a global health threat. This study aimed to investigate the effectiveness of tocilizumab in COVID-19 patients.Methods:We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform to March 10, 2021 for randomized controlled trials in which patients were randomly assigned to receive tocilizumab plus usual care or usual care alone in hospitalized adults with COVID-19. A random-effects meta-analysis model was used to pool studies. All data analyses were performed using Review Manager version 5.4.Results:Eleven studies with 6579 patients were included in our meta-analysis, of which 3406 and 3173 were assigned to tocilizumab and control groups, respectively. Tocilizumab significantly reduced the 28 to 30-day mortality (relative risk [RR] = 0.89, 95% confidence interval [CI] 0.80-0.99, P = .04), incidence of mechanical ventilation (MV) (RR = 0.79, 95% CI 0.71-0.89, P < .001), composite outcome of MV or death (RR = 0.81, 95% CI 0.72-0.90, P < .001), time-to-hospital discharge (hazard ratio = 1.30, 95% CI 1.16-1.45, P < .001), intensive care unit admission (RR = 0.64, 95% CI 0.47-0.88, P = .006), serious infection (RR = 0.61, 95% CI 0.40-0.94, P = .02), and number of serious adverse events (RR = 0.64, 95% CI 0.47-0.86, P = .004).Conclusion:Tocilizumab reduced short-term mortality, incidence of MV, composite outcome of death or MV, intensive care unit admission, serious infection, serious adverse events, and time-to-hospital discharge in hospitalized COVID-19 patients. Further studies are required to determine the optimal dose.     

Use of traditional Chinese medicine as an adjunctive treatment for COVID-19: A systematic review and meta-analysis

Background:This review aims to evaluate the supportive effects of frequently used traditional Chinese medicine (TCM) for the treatment of coronavirus disease 2019 (COVID-19).Methods:Five databases were searched through July 7, 2020. Randomized controlled trials investigating the efficacy of TCM for use in the treatment of COVID-19 were included. Newcastle–Ottawa Scale (NOS) and modified Jadad score were used for the evaluation of the methodological quality of the included studies. Weighted mean difference, odds ratio (OR), and 95% confidence interval (95% CI) were calculated for pooling out results. Data were extracted for conducting a meta-analysis using STATA version 12.0.Results:Eight studies with a total of 750 patients were included in this meta-analysis. All included trial groups involved treatment with TCM and Western medicine, while the control groups were treated only with Western medicine. The intervention therapy significantly improved the overall effective rate (n = 346, OR = 2.5, 95% CIs = 1.46–4.29), fever symptom disappearance rate (n = 436; OR = 3.6; 95% CIs = 2.13–6.08), fatigue symptom disappearance rate (n = 436; OR = 3.04; 95% CIs = 1.76–5.26), cough symptom disappearance rate (n = 436; OR = 2.91; 95% CIs = 1.36–6.19), and sputum production reduction (n = 436; OR = 5.51; 95% CIs = 1.94–15.64). Based on the Newcastle–Ottawa Scale assessment, 6 studies received a score of 4, and 1 study achieved a score of 5. One study was assessed using the modified Jadad score, achieving a score of 6.Conclusions:The integration of TCM with Western medicine has significantly improved the treatment for COVID-19 patients compared to Western medicine treatment alone. Combined therapy using TCM and Western medicine revealed the potential adjunctive role of TCM in treating COVID-19. However, high-quality clinical studies are still required to further evaluate the efficacy and safety of TCM in the treatment of COVID-19.     

Clinical predictive risk factors prolonged the duration of SARS-CoV-2 clearance in 279 moderate COVID-19 patients: A multicenter retrospective cohort study

The results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid as one of the criteria has been widely applied to assess whether the coronavirus disease 2019 (COVID-19) patients could discharge, however, the risk factors that affect the duration of the SARS-CoV-2 clearance remained to be an enigma. Our research was to identify risk factors correlated with prolonged duration of the SARS-CoV-2 clearance in moderate COVID-19 patients.We retrospectively analyzed 279 consecutive ordinary COVID-19 patients in 3 hospitals in Hubei province including Huangshi Hospital of Infectious Disease, Wuhan Thunder God Mountain Hospital, and Tongji Hospital. Eight clinical characters were contained as risk factors. We used a logistic regression model and nomogram to assess the possibility that the SARS-CoV-2 nucleic acid may turn negative in 14 days.Time from symptoms onset to diagnosis (odds ratio [OR] = 3.18; 95% confidence interval [CI] 1.56–6.46; P = .001), time from onset use of antiviral drugs to onset of symptoms (OR = 0.41; 95% CI 0.23–0.72; P = .02), and bacterial coinfection (OR = 0.07; 95% CI 0.01–0.86; P = .038) were independent risks factors for the duration of SARS-CoV-2 nucleic acid clearance. The regression model showed good accuracy and sensitivity (area under the curve  = 0.96). Nomogram was also provided to predict the negative conversion rate of SARS-CoV-2 nucleic acids within 14 days.Time from symptoms onset to diagnosi, time from onset use of antiviral drugs to onset of symptoms, and bacterial coinfection were independent risk factors for the time of SARS-CoV-2 nucleic acid turning negative in ordinary COVID-19 patients. However, the age, gender, underlying disease, fungal coinfection, and duration use of antiviral drugs were irrelevant factors.     

Clinical features and prognostic factors of critically ill patients with COVID-19 in Daegu,South Korea: A multi-center retrospective study

To describe the clinical and demographic characteristics of critically ill patients with COVID-19 in Daegu, South Korea, and to explore the risk factors for in-hospital mortality in these patients.Retrospective cohort study of 110 critically ill patients with COVID-19 admitted to the ICU in Daegu, South Korea, between February 18 and April 5, 2020. The final date of follow-up was April 20, 2020.A total of 110 patient medical records were reviewed. The median age was 71 years (interquartile range [IQR] = 63–78 years). During the study period, 47 patients (42.7%) died in the hospital. The most common SARS-CoV-2 infection related complication was acute respiratory distress syndrome (ARDS) in 95 patients (86.4%). Of the 79 patients (71.8%) who received invasive mechanical ventilation, 46 (58.2%) received neuromuscular blockade injection, and 19 (24.1%) received ECMO treatment. All patients received antibiotic injection, 99 patients (90%) received hydroxychloroquine, 96 patients (87.3%) received lopinavir-ritonavir antiviral medication, and 14 patients (12.7%) received other antiviral agents, including darunavir-cobicistat and emtricitabine-tenofovir. In the multivariable logistic regression model, the odds ratio of in-hospital death was higher with APACHE II score (OR = 1.126; 95% CI = 1.014–1.252; P = .027).The in-hospital mortality rate of critically ill patients with COVID-19 was approximately 40%. Higher APACHE II score at admission was an independent risk factor for death in these patients.     

Effects of Angiotensin Converting Enzyme Inhibition or Angiotensin Receptor Blockade in Dialysis Patients: A Nationwide Data Survey and Propensity Analysis

Long-term benefit of using a renin–angiotensin–aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients already receiving dialysis remains undetermined. The aim of this study is to assess the efficacy and safety of ACEI or ARB use in dialysis patients. We performed a population-based cohort study with time-to-event analyses to estimate the relation between the use of ACEI/ARB and their outcomes. We used a nationwide database (Registry for Catastrophic Illnesses) for Taiwan, which has data from 1995 to 2008 nearly of all patients who received dialysis therapy. The records of all dialysis patients aged ≥18 with no evidence of cardiovascular (CV) events in 1997 and 1998 (133,564 patients) were examined. Users (n = 50,961) and nonusers (n = 59,913) of an ACEI/ARB were derived. We then used propensity score matching and Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) for all-cause mortality and CV events in users and nonusers of an ACRI/ARB. The 15,182 patients, who used an ACEI/ARB, and the 15,182 nonusers had comparable baseline characteristics during the 14 years of follow-up. The mortality was significantly greater in patients who did not use an ACEI/ARB (HR = 0.90, 95% confidence interval = 0.86–0.93). Subgroup analysis of 3 tertiles of patients who used different total amounts of ACEI/ARB during the study period indicated that CV events were more common in patients who used an ACEI/ARB for a short duration (tertile 1: HR = 1.63), but less common in those who used an ACEI/ARB for long durations (tertile 2: HR = 1.05; tertile 3: HR = 0.94; trend for declining HR from tertile 1 to 3: P < 0.001). The mortality benefit provided by use of an ACEI/ARB was consistent across most patient subgroups, as was the benefit of ARB monotherapy rather than ACEI monotherapy. Independent of traditional risk factors, overall mortality was significantly lower in dialysis patients who used an ACEI/ARB. In addition, subjects who used an ACEI/ARB for longer durations were significantly less likely to experience CV events.     

Risk factors associated with the need for oxygen therapy in patients with COVID-19

Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30–60 years), and the median modified early warning score at admission was 1 (IQR, 1–2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686–34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010–1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008–1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073–1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870–5.382, P < .001) were associated with oxygen therapy.In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.     

Age-adjusted Charlson comorbidity index score is the best predictor for severe clinical outcome in the hospitalized patients with COVID-19 infection

Aged population with comorbidities demonstrated high mortality rate and severe clinical outcome in the patients with coronavirus disease 2019 (COVID-19). However, whether age-adjusted Charlson comorbidity index score (CCIS) predict fatal outcomes remains uncertain.This retrospective, nationwide cohort study was performed to evaluate patient mortality and clinical outcome according to CCIS among the hospitalized patients with COVID-19 infection. We included 5621 patients who had been discharged from isolation or had died from COVID-19 by April 30, 2020. The primary outcome was composites of death, admission to intensive care unit, use of mechanical ventilator or extracorporeal membrane oxygenation. The secondary outcome was mortality. Multivariate Cox proportional hazard model was used to evaluate CCIS as the independent risk factor for death.Among 5621 patients, the high CCIS (≥ 3) group showed higher proportion of elderly population and lower plasma hemoglobin and lower lymphocyte and platelet counts. The high CCIS group was an independent risk factor for composite outcome (HR 3.63, 95% CI 2.45–5.37, P < .001) and patient mortality (HR 22.96, 95% CI 7.20–73.24, P < .001). The nomogram showed that CCIS was the most important factor contributing to the prognosis followed by the presence of dyspnea (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.16–3.83), low body mass index < 18.5 kg/m² (HR 2.36, CI 1.49–3.75), lymphopenia (<0.8 x10⁹/L) (HR 2.15, CI 1.59–2.91), thrombocytopenia (<150.0 x10⁹/L) (HR 1.29, CI 0.94–1.78), anemia (<12.0 g/dL) (HR 1.80, CI 1.33–2.43), and male sex (HR 1.76, CI 1.32–2.34). The nomogram demonstrated that the CCIS was the most potent predictive factor for patient mortality.The predictive nomogram using CCIS for the hospitalized patients with COVID-19 may help clinicians to triage the high-risk population and to concentrate limited resources to manage them.     

Association between the peripheral blood eosinophil counts and COVID-19: A meta-analysis

Background:The conclusions about the relationship between eosinophil counts and the severity of coronavirus disease 2019 (COVID-19) were controversial, so we updated the evidences and reassessed it.Methods:We searched the PubMed, Cochrane library, Excerpta Medica Database, and Web of Science to compare the eosinophil counts about non-severe disease group (mild pneumonia, moderate pneumonia, non-critical disease and recovery group) and severe disease group (severe pneumonia, critical pneumonia, critical disease and death group) in COVID-19.Results:A total of 1228 patients from 10 studies were included. Compared with non-severe group, severe group had strikingly lower average eosinophil counts (SMD 0.65, 95% confidence intervals [CI] 0.29–1.01; P < .001). The result of subgroup analysis of different countries showed SMD 0.66, 95% CI 0.26–1.06; P < .001. Another subgroup analysis between mild-moderate pneumonia versus severe-critical pneumonia showed SMD 0.69, 95% CI 0.25–1.13; P < .001, and no significant risk of publication bias (Begg test 0.063 and Egger test 0.057) in this subgroup. The heterogeneity was substantial, but the sensitivity analyses showed no significant change when individual study was excluded, which suggested the crediblity and stablity of our results.Conclusions:The eosinophil counts had important value as an indicator of severity in patients with COVID-19.PROSPERO registration number:CRD42020205497.     

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials

Background: Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs).Methods and analysis: We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes.Results: A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61–3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08–3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29–0.74), shorten the duration of fever (MD = −1.00, 95% CI −1.17 to −0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone.Conclusion: Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.     

Obesity or increased body mass index and the risk of severe outcomes in patients with COVID-19: A protocol for systematic review and meta-analysis

Background:To assess the effect of obesity or a high body mass index (BMI) on the risk of severe outcomes in patients with coronavirus disease 2019 (COVID-19).Methods:Studies on the relationship between BMI or obesity and COVID-19 since December 2019. The odds ratio (OR) and weighted mean difference (WMD) with their 95% confidence intervals (CIs) were used to assess the effect size.Results:BMI was significantly increased in COVID-19 patients with severe illness (WMD: 1.18; 95% CI: 0.42–1.93), who were admitted to an intensive care unit (ICU) (WMD: 1.46; 95% CI: 0.96–1.97), who required invasive mechanical ventilation (IMV) (WMD: 2.70, 95% CI: 1.05–4.35) and who died (WMD: 0.91, 95% CI: 0.02–1.80). In Western countries, obesity (BMI of ≥30 kg/m²) increased the risk of hospitalization (OR: 2.08; 95% CI: 1.22–3.54), admission to an ICU (OR: 1.54; 95% CI: 1.29–1.84), need for IMV (OR: 1.73, 95% CI: 1.38–2.17), and mortality (OR: 1.43; 95% CI: 1.17–1.74) of patients with COVID-19. In the Asian population, obesity (BMI of ≥28 kg/m²) increased the risk of severe illness (OR: 3.14; 95% CI: 1.83–5.38). Compared with patients with COVID-19 and a BMI of <25 kg/m², those with a BMI of 25–30 kg/m² and ≥30 kg/m² had a higher risk of need for IMV (OR: 2.19, 95% CI: 1.30–3.69 and OR: 3.04; 95% CI: 1.76–5.28, respectively). The risk of ICU admission in patients with COVID-19 and a BMI of ≥30 kg/m² was significantly higher than in those with a BMI of 25–30 kg/m² (OR: 1.49; 95% CI: 1.00–2.21).Conclusion:As BMI increased, the risks of hospitalization, ICU admission, and need for IMV increased, especially in COVID-19 patients with obesity.Ethics and dissemination:This systematic review and meta-analysis does not require an ethics approval as it does not collect any primary data from patients.     

Corticosteroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Background:Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19.Methods:We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection.Results:A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections.Conclusion:Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.