Mortality In Coronavirus Disease 2019 Patients Research Articles

Association of smoking history with severe and critical outcomes in COVID-19 patients: A systemic review and meta-analysis

IntroductionThe highly infectious coronavirus disease 2019 (COVID-19) has now rapidly spread around the world. This meta-analysis was strictly focused on the influence of smoking history on the severe and critical outcomes on people with COVID-19 pneumonia. MethodsA systematic literature search was conducted in eight online databases up to 1 February 2021. All studies meeting our selection criteria were included and evaluated. Stata 14.0 software was used to analyze the data. ResultsA total of 109 articles involving 517,020 patients were included in this meta-analysis. A statistically significant association was discovered between smoking history and COVID-19 severity, the pooled OR was 1.55 (95%CI: 1.41-1.71). Smoking was significantly associated with the risk of admission to intensive care unit (ICU) (OR=1.73, 95%CI: 1.36-2.19), increased mortality (OR=1.58, 95%CI: 1.38-1.81), and critical diseases composite endpoints (OR=1.61, 95%CI: 1.35-1.93), whereas there was no relationship with mechanical ventilation. The pooled prevalence of smoking using the random effects model (REM) was 15% (95%CI: 14%-16%). Meta-regression analysis showed that age (P=0.004), hypertension (P=0.007), diabetes (P=0.029), chronic obstructive pulmonary disease (COPD) (P=0.001) were covariates that affect the association. ConclusionsSmoking was associated with severe or critical outcomes and increased the risk of admission to ICU and mortality in COVID-19 patients, but not associated with mechanical ventilation. This association was more significant for former smokers than in current smokers. Current smokers also had a higher risk of developing severe COVID-19 compared with non-smokers. More detailed data, which are representative of more countries, are needed to confirm these preliminary findings.

The Potential Role of Lithium as an Antiviral Agent against SARS-CoV-2 via Membrane Depolarization: Review and Hypothesis

Studies on potential treatments of Coronavirus Disease 2019 (COVID-19) are important to improve the global situation in the face of the pandemic. This review proposes lithium as a potential drug to treat COVID-19. Our hypothesis states that lithium can suppress NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activity, inhibit cell death, and exhibit immunomodulation via membrane depolarization. Our hypothesis was formulated after finding consistent correlations between these actions and membrane depolarization induced by lithium. Eventually, lithium could serve to mitigate the NLRP3-mediated cytokine storm, which is allegedly reported to be the inciting event of a series of retrogressive events associated with mortality from COVID-19. It could also inhibit cell death and modulate the immune system to attenuate its release, clear the virus from the body, and interrupt the cycle of immune-system dysregulation. Therefore, these effects are presumed to improve the morbidity and mortality of COVID-19 patients. As the numbers of COVID-19 cases and deaths continue to rise exponentially without a clear consensus on potential therapeutic agents, urgent conduction of preclinical and clinical studies to prove the efficacy and safety of lithium is reasonable.

Impact of COPD on COVID-19 prognosis: A nationwide population-based study in South Korea

Underlying chronic respiratory disease may be associated with the severity of coronavirus disease 2019 (COVID-19). This study investigated the impact of chronic obstructive pulmonary disease (COPD) on the risk for respiratory failure and mortality in COVID-19 patients. A nationwide retrospective cohort study was conducted in 4610 patients (≥ 40 years old) infected with COVID-19 between January 20 and May 27, 2020, using data from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The clinical course and various clinical features were compared between COPD and non-COPD patients, and the risks of respiratory failure and all-cause mortality in COPD patients were analyzed using a multivariate logistic regression model. Among 4610 COVID-19 patients, 4469 (96.9%) and 141 (3.1%) were categorized into the non-COPD and COPD groups, respectively. The COPD group had greater proportions of older (≥ 60 years old) (78.0% vs. 45.2%, P < 0.001) and male (52.5% vs. 36.6%, P < 0.001) patients than the non-COPD group. Relatively greater proportions of patients with COPD received intensive critical care (7.1% vs. 3.7%, P = 0.041) and mechanical ventilation (5.7% vs. 2.4%, P = 0.015). Multivariate analyses showed that COPD was not a risk factor for respiratory failure but was a significant independent risk factor for all-cause mortality (OR = 1.80, 95% CI 1.11–2.93) after adjustment for age, sex, and Charlson Comorbidity Index score. Among COVID-19 patients, relatively greater proportions of patients with COPD received mechanical ventilation and intensive critical care. COPD is an independent risk factor for all-cause mortality in COVID-19 patients in Korea.

Predictive Value of CAR for In-Hospital Mortality in Patients with COVID-19 Pneumonia: A Retrospective Cohort Study

BackgroundIn the current literature, there is a growing evidence that supports the significant role of inflammation in the progression of viral pneumonia, including patients with coronavirus disease 2019 (COVID-19).AimThe present study aimed to investigate the predictive value of C-reactive protein/albumin ratio (CAR) for in-hospital mortality in patients with COVID-19.Material and MethodsThis retrospective study included the data of 275 consecutive COVID-19 patients who were hospitalized in a referral pandemic center. The CAR ratio was obtained by dividing the CRP level with albumin level. The study population was divided into tertiles (T1, T2, and T3) according to their admission CAR values. The endpoint of the study was a composite outcome of in-hospital mortality.ResultsDuring the in-hospital course, 33 (12%) patients died. The patients classified into T3 group had significantly higher CAR compared those classified into T2 and T1 groups. After the adjustment for the confounders, T3 group had 8.2 (95% CI: 4.2–48.1) times higher rates of in-hospital mortality compared to T1 group (the reference group) in a logistic regression model using CAR values.ConclusionTo the best of our knowledge, this is the first study to demonstrate the predictive value of CAR for in-hospital mortality in COVID-19 patients.

Prognostic Value of Right Ventricular Ejection Fraction Assessed by 3D Echocardiography in COVID-19 Patients.

Background: RVEF (right ventricular ejection fraction) measured by three-dimensional echocardiography (3DE) has been used in evaluating right ventricular (RV) function and can provide useful prognostic information in other various cardiovascular diseases. However, the prognostic value of 3D-RVEF in coronavirus disease 2019 (COVID-19) remains unknown. We aimed to investigate whether 3D-RVEF can predict the mortality of COVID-19 patients.Methods: A cohort of 128 COVID-19-confirmed patients who had undergone echocardiography were studied. Thirty-one healthy volunteers were also enrolled as controls. COVID-19 patients were divided into three subgroups (general, severe, and critical) according to COVID-19 severity-of-illness. Conventional RV structure and function parameters, RV free wall longitudinal strain (FWLS) and 3D-RVEF were acquired. RVFWLS was measured by two-dimensional speckle tracking echocardiography. RVEF was acquired by 3DE.Results: Compared with controls, 2D-RVFWLS and 3D-RVEF were both significantly decreased in COVID-19 patients (−27.2 ± 4.4% vs. −22.9 ± 4.8%, P < 0.001; 53.7 ± 4.5% vs. 48.5 ± 5.8%, P < 0.001). Critical patients were more likely to have a higher incidence of acute cardiac injury and acute respiratory distress syndrome (ARDS), and worse prognosis than general and severe patients. The critical patients exhibited larger right-heart chambers, worse RV fractional area change (RVFAC), 2D-RVFWLS, and 3D-RVEF and higher proportion of pulmonary hypertension than general and severe patients. Eighteen patients died during a median follow-up of 91 days. The multivariate Cox regression analysis revealed the acute cardiac injury, ARDS, RVFAC, RVFWLS, and 3D-RVEF were independent predictors of death. 3D-RVEF (chi-square to improve 18.3; P < 0.001), RVFAC (chi-square to improve 4.5; P = 0.034) and 2D-RVFWLS (chi-square to improve 5.1; P = 0.024) all provided additional prognostic value of higher mortality over clinical risk factors. Moreover, the incremental predictive value of 3D-RVEF was significantly (P < 0.05) higher than RVFAC and RVFWLS.Conclusion: 3D-RVEF was the most robust independent predictor of mortality in COVID-19 patients and provided a higher predictive value over conventional RV function parameters and RVFWLS, which may be helpful to identify COVID-19 patients at a higher risk of death.

Severity of liver test abnormalities in coronavirus disease 2019 depends on comorbidities and predicts early in-hospital mortality.

Liver chemistry abnormalities (LCA) are common in patients with coronavirus disease 2019 (COVID-19), but their causes and clinical impact have not been adequately studied. We assessed the associations between LCA and clinical characteristics, inflammatory serum markers, in-hospital mortality. Ten thousand eight hundred fifty-six adult patients with COVID-19 hospitalized in 13 hospitals in New York (1 March to 27 April 2020) were analyzed retrospectively. Abnormalities of liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, or total bilirubin] were defined as absent, mild-moderate (at least one value up to four times elevated), or severe. LCA were mild-moderate in 63.9% and severe in 7.6% at admission. Risk factors for severe LCA were male sex and chronic liver disease. Conversely, hypertension and diabetes mellitus were less likely associated with severe LCA. AST elevation correlated weakly to modestly with inflammatory markers. On adjusted analysis, in-hospital mortality was 1.56 times and 1.87 times increased in patients with mild-to-moderate and severe LCA, respectively. Diabetes, hypertension, male sex, and age greater than 60 years was associated with incremental risk of mortality with increase severity of LCA, especially in the first week of hospitalization. HTN was not associated with increased in-hospital mortality unless LCA was present. Increasing severity of LCA on hospital admission predicts early in-hospital mortality in COVID-19 patients. Mortality associated with the known risk factors, hypertension, diabetes, male sex, and old age was accentuated in the presence of LCA. AST correlated modestly with inflammatory markers.

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience

BackgroundThe spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities. MethodsRetrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value. Results426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55–17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent. Conclusionshs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.

Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has posed a serious threat to global public health security. With the increase in the number of confirmed cases globally, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Despite atypical pneumonia as the primary symptom, liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19, like severe acute respiratory syndrome and Middle East respiratory syndrome. Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection, which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.

Biventricular Longitudinal Strain Predict Mortality in COVID-19 Patients.

Background: Biventricular longitudinal strain has been recently demonstrated to be predictive of poor outcomes in various cardiovascular settings. Therefore, this study sought to investigate the prognostic implications of biventricular longitudinal strain in patients with coronavirus disease 2019 (COVID-19).Methods: We enrolled 132 consecutive patients with COVID-19. Left ventricular global longitudinal strain from the apical four-chamber views (LV GLS4CH) and right ventricular free wall longitudinal strain (RV FWLS) were obtained using two-dimensional speckle-tracking echocardiography.Results: Compared with patients without cardiac injury, those with cardiac injury had higher levels of coagulopathy and inflammatory biomarkers, higher incidence of complications, more mechanical ventilation therapy, and higher mortality. Patients with cardiac injury displayed decreased LV GLS4CH and RV FWLS, elevated pulmonary artery systolic pressure, and higher proportion of pericardial effusion. Higher biomarkers levels of inflammation and cardiac injury, and the presence of pericardial effusion were correlated with decreases in LV GLS4CH and RV FWLS. During hospitalization, 19 patients died. Compared with survivors, LV GLS4CH and RV FWLS were impaired in non-survivors. At a 3-month follow-up after discharge, significant improvements were observed in LV GLS4CH and RV FWLS. Multivariate Cox analysis revealed that LV GLS4CH [hazard ratio: 1.41; 95% confidence interval [CI]: 1.08 to 1.84; P = 0.011] and RV FWLS (HR: 1.29; 95% CI: 1.09–1.52; P = 0.003) were independent predictors of higher mortality in patients with COVID-19.Conclusions: LV GLS4CH and RV FWLS are independent and strong predictors of higher mortality in COVID-19 patients and can track improvement during the convalescent phase of their illness. Therefore, biventricular longitudinal strain may be crucial for risk stratification and serial follow-up in patients with COVID-19.

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality.

BackgroundCoronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.ObjectivesTo correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.MethodsConsecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.ResultsStudy enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428–596) compared to non-critical patients (288%, 230–350, p < 0.0001) or COVID-19 outpatients (144%, 133–198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86–1.09) compared to non-critical patients (0.96, 1.04–1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan–Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and d-dimer levels.ConclusionVWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.

Characterizing the immune responses of those who survived or succumbed to COVID-19: Can immunological signatures predict outcome?

BackgroundImmunodeficiency has pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Several studies have indicated defects in the immune system of COVID-19 patients at different disease stages. Therefore, this study investigated whether alters in immune responses of COVID-19 patients may be considered as predicting factors for disease outcome. MethodsThe percentages of innate and adoptive immune cells in the recovered and dead patients with COVID-19, and healthy subjects were determined by flow cytometry. The levels of pro- and anti-inflammatory cytokines and other immune factors were also measured by enzyme-linked immunosorbent assay. ResultsAt the first day of hospitalization, the frequencies of CD56dim CD16+ NK cells and CD56bright CD16dim/− NK cells in patients who died during treatment were significantly increased compared to recovered and healthy individuals (P < 0.0001). The recovered and dead patients had a significant increase in monocyte number in comparison with healthy subjects (P < 0.05). No significant change was observed in Th1 cell numbers between the recovered and dead patients while Th2, Th17 cell, and Treg percentages in death cases were significantly lower than healthy control and those recovered, unlike exhausted CD4 + and CD8 + T cells and activated CD4 + T cells (P < 0.0001–0.05). The activated CD8 + T cell was significantly higher in the recovered patients than healthy individuals (P < 0.0001–0.05). IL-1α, IL-1β, IL-6, and TNF-α levels in patients were significantly increased (P < 0.0001–0.01). However, there were no differences in TNF-α and IL-1β levels between dead and recovered patients. Unlike TGF-β1 level, IL-10 was significantly increased in recovered patients (P < 0.05). Lymphocyte numbers in recovered patients were significantly increased compared to dead patients, unlike ESR value (P < 0.001–0.01). CRP value in recovered patients significantly differed from dead patients (P < 0.001). ConclusionChanges in frequencies of some immune cells and levels of some immune factors may be considered as predictors of mortality in COVID-19 patients.

Is prognostic nutritional index a predictive marker for estimating all-cause in-hospital mortality in COVID-19 patients with cardiovascular risk factors?

BackgroundThis study examined the possible association between the prognostic nutritional index (PNI) and in-hospital mortality rates in cases with a high cardiovascular risk burden and hospitalized with the diagnosis of coronavirus disease 2019 (COVID-19). Material and MethodsThis retrospective and cross-sectional study included 294 COVID-19 patients hospitalized in a tertiary referral pandemic center. The study cohort was grouped into tertiles based on the initial PNI values as T1, T2, and T3. The PNI was calculated for each case and the prognostic value of this index was compared to CURB-65 and 4C mortality risk scores in predicting in-hospital mortality. ResultsPatients stratified into the T1 tertile had a lower lymphocyte count, serum albumin level, and PNI values. In a multivariate analysis, the PNI (OR: 0.688,%95CI: 0.586–0.808, p < 0.001) was an independent predictor for all-cause in-hospital death. After adjusting for confounding independent parameters, patients included in the T1 tertile were found to have 11.2 times higher rates of in-hospital mortality compared to the T3 group, which was presumed as the reference group. In addition, we found that the area under curve (AUC) value of PNI was significantly elevated than that of serum albumin level and total lymphocyte counts alone. [(AUC):0.79 vs AUC:0.75 vs AUC:0.69; respectively). ConclusionThis study demonstrated that the PNI is independently related with in-hospital mortality in patient with COVID-19 and cardiovascular risk factors. The power of the PNI was also validated using well-accepted risk scores of COVID-19 such as CURB-65 and 4C mortality risk scores.

Pre-existing Health Conditions and Epicardial Adipose Tissue Volume: Potential Risk Factors for Myocardial Injury in COVID-19 Patients.

Background: Myocardial injury is a life-threatening complication of coronavirus disease 2019 (COVID-19). Pre-existing health conditions and early morphological alterations may precipitate cardiac injury and dysfunction after contracting the virus. The current study aimed at assessing potential risk factors for COVID-19 cardiac complications in patients with pre-existing conditions and imaging predictors.Methods and Results: The multi-center, retrospective cohort study consecutively enrolled 400 patients with lab-confirmed COVID-19 in six Chinese hospitals remote to the Wuhan epicenter. Patients were diagnosed with or without the complication of myocardial injury by history and cardiac biomarker Troponin I/T (TnI/T) elevation above the 99th percentile upper reference limit. The majority of COVID-19 patients with myocardial injury exhibited pre-existing health conditions, such as hypertension, diabetes, hypercholesterolemia, and coronary disease. They had increased levels of the inflammatory cytokine interleukin-6 and more in-hospital adverse events (admission to an intensive care unit, invasive mechanical ventilation, or death). Chest CT scan on admission demonstrated that COVID-19 patients with myocardial injury had higher epicardial adipose tissue volume ([EATV] 139.1 (83.8–195.9) vs. 92.6 (76.2–134.4) cm2; P = 0.036). The optimal EATV cut-off value (137.1 cm2) served as a useful factor for assessing myocardial injury, which yielded sensitivity and specificity of 55.0% (95%CI, 32.0–76.2%) and 77.4% (95%CI, 71.6–82.3%) in adverse cardiac events, respectively. Multivariate logistic regression analysis showed that EATV over 137.1 cm2 was a strong independent predictor for myocardial injury in patients with COVID-19 [OR 3.058, (95%CI, 1.032–9.063); P = 0.044].Conclusions: Augmented EATV on admission chest CT scan, together with the pre-existing health conditions (hypertension, diabetes, and hyperlipidemia) and inflammatory cytokine production, is associated with increased myocardial injury and mortality in COVID-19 patients. Assessment of pre-existing conditions and chest CT scan EATV on admission may provide a threshold point potentially useful for predicting cardiovascular complications of COVID-19.

An immune-based biomarker signature is associated with mortality in COVID-19 patients.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

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

BackgroundTo develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC).MethodsWe performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM).FindingsFive risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92–0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions.ConclusionsThe PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients.FundingThis work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

Extracorporeal Membrane Oxygenation in COVID-19-Related Acute Respiratory Distress Syndrome – A EuroELSO International Survey

Extracorporeal membrane oxygenation (ECMO) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic Coronavirus Disease 2019 (COVID-19) with ECMO have been restrained. In the meantime, ECMO has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality.Objective: We performed an international email survey to assess how ECMO providers worldwide have previously used ECMO during the treatment of critically ill patients with COVID-19.MethodsA questionnaire with 45 questions (covering e.g. indication, technical aspects, benefit and reasons for treatment discontinuation), mostly multiple-choice, was distributed by email to ECMO centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO).Results: 276 centers worldwide responded that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECMO was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECMO varied between less than two and more than four weeks. The main reason to discontinue ECMO treatment prior to patient’s recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators were responsible for discontinuation of ECMO support. Most ECMO physicians (66% ± 26%) agreed that patients with COVID-19 induced ARDS (CARDS) benefitted from ECMO. Overall mortality of COVID-19 patients on ECMO was estimated to be about 55%, scoring higher than what has previously been reported for Influenza patients on ECMO (29 – 36%).Conclusion: ECMO has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECMO. Triage situations were rarely a concern. ECMO providers stated that patients with severe COVID-19 benefitted from ECMO. An increasing use in patients with respiratory failure in a future stage of the pandemic may be expected.Funding Statement: COVID-19 research was funded by the Federal state of Saarland, Saarland University and Dr. Rolf M. Schwiete Foundation.Declaration of Interests: Robert Bals declares funding from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis, CLS Behring, the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), Sander-Stiftung, Schwiete-Stiftung, Krebshilfe and Mukoviszidose eV. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. All other authors: No potential conflicts of interest.Ethics Approval Statement: The ethical committee (Ärztekammer des Saarlandes) waived the need for a formal approval since the questionnaire did not retrieve actual patient data.

Roles of certain biochemical and hematological parameters in predicting mortality and ICU admission in COVID-19 patients

In this study, we aimed to retrospectively analyze the roles of certain hematological and biochemical parameters in predicting mortality and intensive care unit admission in patients diagnosed with coronavirus disease 2019 (COVID-19).We analyzed the complete blood count and biochemical parameters of 186 COVID-19 patients by using the polymerase chain reaction test. Whether these parameters can be used to predict intensive care unit admission and mortality in the COVID-19 patients was investigated.The complete blood count and biochemical parameters of COVID-19 patients and in those admitted to intensive care unit were compared. The red cell distribution width, ferritin, lactate dehydrogenase, D-dimer, C-reactive protein, prothrombin time, and creatinine levels were found to be the most significant parameters. We found that these parameters are significant for predicting not only intensive care unit admission, but also the mortality of the patients admitted to the intensive care unit.We determined that the most effective parameters to predict intensive care unit admission and mortality in COVID-19 patients are ferritin, lactate dehydrogenase, D-dimer, C-reactive protein, red cell distribution width, creatinine, and intensive care unit. Close monitoring of these parameters and early intervention in alterations are of vital importance.

Dipeptidyl peptidase-4 inhibitor use and mortality in COVID-19 patients with diabetes mellitus: an updated systematic review and meta-analysis.

Background:Few observational studies have shown a beneficial effect of dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with coronavirus disease 2019 (COVID-19), although results are not consistent. The present systematic review and meta-analysis was undertaken to provide a precise summary of the effect of DPP4i use (preadmission or in-hospital) and mortality in COVID-19 patients with diabetes mellitus (DM).Methods:PubMed and Google Scholar databases were systematically searched using appropriate keywords to 4 January 2021, to identify observational studies reporting mortality in COVID-19 patients with DM using DPP4i versus those not using DPP4i. Preadmission and in-hospital use of DPP4i were considered. Study quality was assessed using the Newcastle–Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Subgroup analysis was performed for studies reporting preadmission and in-hospital use of DPP4i.Results:We identified nine observational studies of high quality pooling data retrieved from 7008 COVID-19 patients with DM. The pooled analysis of unadjusted and adjusted data did not show any significant association between DPP4i use and mortality in COVID-19 patients with DM. However, on subgroup analysis, we found that in-hospital (and not preadmission) DPP4i use was associated with reduced mortality (unadjusted OR 0.37, 95% CI 0.23, 0.58, p < 0.0001, I2 = 0% and adjusted OR 0.27, 95% CI 0.13, 0.55, p = 0.0003, I2 = 12%).Conclusions:In-hospital use of DPP4i is associated with a significant reduction in COVID-19 mortality. Hence, it would be prudent to initiate or continue DPP4i in COVID-19 patients with DM if not contraindicated.

Comparative performance of CHA2DS2VASc and anticoagulation and risk factors in atrial fibrillation risk scores for predicting mortality in patients with COVID-19

Background: The AnTicoagulation and Risk factors in Atrial fibrillation (ATRIA) and CHA2DS2VASc risk scores used to detect the thromboembolic and hemorrhagic risk in atrial fibrillation (AF) patients has been shown recently to predict poor clinical outcomes varies clinical settings, regardless of having AF. We aimed to examine the potential utility of admission CHA2DS2VASc and ATRIA scores for predicting in-hospital mortality in patients with coronavirus disease 2019 (COVID-19). Methods: In this retrospective study hospitalized 134 COVID-19 patients who diagnosed with a positive polymerase chain reaction test, were included. Patients were divided into two groups who were died and survivors, both the groups were compared according to clinical, laboratory, and demographic features, including the CHA2DS2VASc and ATRIA risk score. Predictors of mortality were determined by logistic regression analysis. Results: ATRIA and CHA2DS2VASc risk scores were predicting mortality in COVID-19 patients. Logistic regression analysis showed that ATRIA risk score, AF and chronic obstructive pulmonary disease were an independent predictor of mortality. For an ATRIA score cut off value of 3, the sensitivity was 77.78%, specificity 57.94%, positive predictive value 31.80, and negative predictive value 91.20. For a CHA2DS2VASc score cut-off value of 4, the sensitivity was 44.44%, specificity 83.18%, positive predictive value 40, and negative predictive value 85.60. Conclusion: CHA2DS2-VASc and ATRIA scores can be used as a novel, simple tool for predicting mortality in COVID-19 patients.

Renin-angiotensin-aldosterone system blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis.

Background and aims: Coronavirus disease 2019 (COVID-19) has been observed to cause a high mortality in people with cardiometabolic diseases. Renin–angiotensin–aldosterone system (RAAS) blockers enhance the expression of ACE2, the binding receptor of SARS-CoV-2, and can enhance viral infectivity. We aim to provide a pooled estimate of the effect of RAAS blockers on COVID-19 outcomes.Methods:A literature search was performed using MEDLINE/PubMed, Google Scholar and preprint servers. All clinical studies analyzing the effect of RAAS blockers on clinical outcomes in COVID-19 patients were included in this study. Newcastle–Ottawa scale was used for quality assessment of studies. MOOSE checklist was followed. Mortality and severity outcomes were recorded as pooled odds ratio (OR) with 95% Confidence Intervals (CIs) and level of heterogeneity (I2). Odds of mortality was the primary outcome. Odds of severity, hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV), steroid use and acute kidney injury were the secondary outcomes. Severity outcomes were chosen depending upon the definition used by respective authors. Country-specific variations and effects of individual class of RAAS blockers were also explored.Results:In total 47 published studies were included in the final analysis, with a total of 26,432 patients from 31 studies in mortality analysis and 20,127 patients from 23 studies in severity analysis. No increased risk of mortality [Pooled OR 0.91 (0.65–1.26), I2 = 89%] or severity [Pooled OR 1.08 (0.79–1.46), I2 = 88%] was seen with RAAS blockers. The drug class was protective in hypertension [pooled OR 0.63 (0.46–0.86), I2 = 58%]. Severity of COVID-19 outcomes was high for Europeans [Pooled OR 2.08 (1.52–2.85), I2 = 77%] and US patients [Pooled OR 1.87 (1.62–2.17)]. Nearly 4 times higher risk of hospitalization and 2 times higher risk of ICU admission and MV were observed in US patients. Class-wise, angiotensin receptor blocker use was associated with 1.6 times higher odds of severity, mainly in Europeans.Conclusion:RAAS blockers are not associated with increased mortality in COVID-19 patients and should be continued in hypertensives. US and European patients are at higher risk of severe outcomes. Pharmacogenetic differences may explain the ethnicity-related variations.Plain language summary Effect of RAAS-blocking medicines on COVID-19 Background and aims: Higher deaths have been observed in COVID-19 patients who have other long-term diseases such as heart disease, diabetes, and high blood pressure. Many of these patients are prescribed a class of medicines called RAAS blockers (ramipril, telmisartan, etc). We studied whether the use of these medicines worsens the course of COVID-19 disease in these patients or causes excess deaths.Methods: We conducted a pooled analysis of 47 observational studies on the use of RAAS blocker drugs in COVID-19 patients.Results: We found that RAAS blockers do not cause excess deaths in patients with COVID-19. On the contrary, they have benefits if prescribed to those with high blood pressure. We also found that whereas European and US patients of COVID-19 taking these medicines had higher disease severity, this was not the case for Chinese patients.Conclusion: Theremay be some genetic and other factors responsible for differences by ethnicity.