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

ObjectiveAssociation 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.MethodsWe 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.ResultsAmong 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.ConclusionsThere 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.     

Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients. Here, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients.MethodsA literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI).ResultsA total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72–1.04; I² = 75.52% and 1.87; 95%CI 1.25–2.49; I² = 97.81%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.74 (95%CI 0.98–7.66).ConclusionHigh NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.     

Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis

BackgroundIn this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia.MethodsWe performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19.ResultsThere were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I²: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I²: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I²: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I²: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I²: 0%).ConclusionCardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.     

Characteristics,Treatment Patterns,and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic,March to October 2020

ObjectiveTo compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic.Patients and MethodsThe study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre–COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames.ResultsThe adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre–COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre–COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05).ConclusionThe findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre–COVID-19 time frame.     

Impact of a High-Risk,Ambulatory COVID-19 Remote Patient Monitoring Program on Utilization,Cost, and Mortality

ObjectiveTo evaluate care utilization, cost, and mortality among high-risk patients enrolled in a coronavirus disease 2019 (COVID-19) remote patient monitoring (RPM) program.MethodsThis retrospective analysis included patients diagnosed with COVID-19 at risk for severe disease who enrolled in the RPM program between March 2020 and October 2021. The program included in-home technology for symptom and physiologic data monitoring with centralized care management. Propensity score matching established matched cohorts of RPM-engaged (defined as ≥1 RPM technology interactions) and non-engaged patients using a logistic regression model of 59 baseline characteristics. Billing codes and the electronic death certificate system were used for data abstraction from the electronic health record and reporting of care utilization and mortality endpoints.ResultsAmong 5796 RPM-enrolled patients, 80.0% engaged with the technology. Following matching, 1128 pairs of RPM-engaged and non-engaged patients comprised the analysis cohorts. Mean patient age was 63.3 years, 50.9% of patients were female, and 81.9% were non-Hispanic White. Patients who were RPM-engaged experienced significantly lower rates of 30-day, all-cause hospitalization (13.7% vs 18.0%, P=.01), prolonged hospitalization (3.5% vs 6.7%, P=.001), intensive care unit admission (2.3% vs 4.2%, P=.01), and mortality (0.5% vs 1.7%; odds ratio, 0.31; 95% CI, 0.12 to 0.78; P=.01), as well as cost of care ($2306.33 USD vs $3565.97 USD, P=0.04), than those enrolled in RPM but non-engaged.ConclusionHigh-risk COVID-19 patients enrolled and engaged in an RPM program experienced lower rates of hospitalization, intensive care unit admission, mortality, and cost than those enrolled and non-engaged. These findings translate to improved hospital bed access and patient outcomes.     

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank.ResultsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2–1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6–2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2–2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2–2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8–3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2–1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors.ConclusionsThe major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.     

Type 2 Diabetes and COVID-19–Related Mortality in the Critical Care Setting: A National Cohort Study in England,March–July 2020

OBJECTIVETo describe the relationship between type 2 diabetes and all-cause mortality among adults with coronavirus disease 2019 (COVID-19) in the critical care setting.RESEARCH DESIGN AND METHODSThis was a nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between 1 March 2020 and 27 July 2020. Cox proportional hazards models were used to estimate 30-day in-hospital all-cause mortality associated with type 2 diabetes, with adjustment for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease).RESULTSA total of 19,256 COVID-19–related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70 years) and 5,447 ICU (mean age 58 years) admissions. Of those admitted, 3,524 (18.3%) had type 2 diabetes and 5,077 (26.4%) died during the study period. Patients with type 2 diabetes were at increased risk of death (adjusted hazard ratio [aHR] 1.23 [95% CI 1.14, 1.32]), and this result was consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with higher age (age 18–49 years aHR 1.50 [95% CI 1.05, 2.15], age 50–64 years 1.29 [1.10, 1.51], and age ≥65 years 1.18 [1.09, 1.29]; P value for age–type 2 diabetes interaction = 0.002).CONCLUSIONSType 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.     

Intravenous bamlanivimab use associates with reduced hospitalization in high-risk patients with mild to moderate COVID-19

BACKGROUNDClinical data to support the use of bamlanivimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) are needed.METHODS2335 Patients who received single-dose bamlanivimab infusion between November 12, 2020, and February 17, 2021, were compared with a propensity-matched control of 2335 untreated patients with mild to moderate COVID-19 at Mayo Clinic facilities across 4 states. The primary outcome was the rate of hospitalization at days 14, 21, and 28.RESULTSThe median age of the population was 63 years; 47.3% of the bamlanivimab-treated cohort were 65 years or more; 49.3% were female and 50.7% were male. High-risk characteristics included hypertension (54.2%), BMI greater than or equal to 35 (32.4%), diabetes mellitus (26.5%), chronic lung disease (25.1%), malignancy (16.6%), and renal disease (14.5%). Patients who received bamlanivimab had lower all-cause hospitalization rates at days 14 (1.5% vs. 3.5%; risk ratio [RR], 0.41), 21 (1.9% vs. 3.9%; RR, 0.49), and 28 (2.5% vs. 3.9%; RR, 0.63). Secondary exploratory outcomes included lower intensive care unit (ICU) admission rates at days 14 (0.14% vs. 1%; RR, 0.14), 21 (0.25% vs.1%; RR, 0.25), and 28 (0.56% vs.1.1%; RR. 0.51) and lower all-cause mortality at days 14 (0% vs. 0.33%), 21 (0.05% vs. 0.4%; RR,0.13), and 28 (0.11% vs. 0.44%; RR, 0.26). Adverse events were uncommon with bamlanivimab, occurring in 19 of 2355 patients, and were most commonly fever (n = 6), nausea (n = 5), and lightheadedness (n = 3).CONCLUSIONSAmong high-risk patients with mild to moderate COVID-19, treatment with bamlanivimab was associated with a statistically significant lower rate of hospitalization, ICU admission, and mortality compared with usual care.FUNDINGMayo Clinic.     

Curbing the Delta Surge: Clinical Outcomes After Treatment With Bamlanivimab-Etesevimab,Casirivimab-Imdevimab,or Sotrovimab for Mild to Moderate Coronavirus Disease 2019

ObjectiveTo describe and compare the clinical outcomes of bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab treatment of mild to moderate coronavirus disease 2019 (COVID-19) during the severe acute respiratory coronavirus 2 (SARS-CoV-2) B.1.617.2 Delta surge.MethodsThis is a retrospective study of high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 between August 1, 2021, and December 1, 2021. Rates of severe disease, hospitalization, intensive care unit admission, and death were assessed.ResultsAmong 10,775 high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for mild to moderate COVID-19 during the Delta surge, 287 patients (2.7%) developed severe disease that led to hospitalization, oxygen supplementation, or death within 30 days after treatment. The rates of severe disease were low among patients treated with bamlanivimab-etesevimab (1.2%), casirivimab-imdevimab (2.9%), and sotrovimab (1.6%; P<.01). The higher rate of severe outcomes among patients treated with casirivimab-imdevimab may be related to a significantly lower COVID-19 vaccination rate in that cohort. Intensive care unit admission was comparable among patients treated bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab (1.0%, 1.0%, and 0.4%, respectively).ConclusionThis real-world study of a large cohort of high-risk patients shows low rates of severe disease, hospitalization, intensive care unit admission, and mortality after treatment with bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 during the SARS-CoV-2 Delta surge.     

Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective,multinational, observational study

PurposeTo determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes.Materials and methodsThis multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality.Results49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33–1.39];1.47 [1.43–1.50], respectively).ConclusionsPatients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.     

Predictive performance of SOFA and qSOFA for in-hospital mortality in severe novel coronavirus disease

ObjectivesThe assessment of illness severity at admission can contribute to decreased mortality in patients with the coronavirus disease (COVID-19). This study was conducted to evaluate the effectiveness of the Sequential Organ Failure Assessment (SOFA) and Quick Sequential Organ Failure Assessment (qSOFA) scoring systems at admission for the prediction of mortality risk in COVID-19 patients.MethodsWe included 140 critically ill COVID-19 patients. Data on demographics, clinical characteristics, and laboratory findings at admission were used to calculate SOFA and qSOFA against the in-hospital outcomes (survival or death) that were ascertained from the medical records. The predictive accuracy of both scoring systems was evaluated by the receiver operating characteristic (ROC) curve analysis.ResultsThe area under the ROC curve for SOFA in predicting mortality was 0.890 (95% CI: 0.826–0.955), which was higher than that of qSOFA (0.742, 95% CI 0.657–0.816). An optimal cutoff of ≥3 for SOFA had sensitivity, specificity, positive predictive value, and negative predictive value of 90.00%, 83.18%, 50.00%, and 97.80%, respectively.ConclusionsThis novel report indicates that SOFA could function as an effective adjunctive risk-stratification tool at admission for critical COVID-19 patients. The performance of qSOFA is accepted but inferior to that of SOFA.     

Vitamin D deficiency is Associated with Increased Risk of Delirium and Mortality among Critically Ill,Elderly Covid-19 Patients

Background and aimData on the associations of vitamin D levels with severe outcomes of coronavirus disease 2019 (COVID-19) among critically ill elderly patients are not conclusive and also no information is available about some outcomes such as delirium. Therefore, the current study was done to assess these associations in critically ill elderly COVID-19 patients.MethodsIn total, 310 critically ill COVID-19 patients, aged ≥ 65 years, were included in the current single center prospective study. All patients were hospitalized in the intensive care unit (ICU). We collected data on demographic characteristics, laboratory parameters, blood pressure, comorbidities, medications, and types of mechanical ventilation at baseline (the first day of ICU admission). Patients were categorized based on serum 25(OH)D3 levels at the baseline [normal levels (>30 ng/mL), insufficiency (20–30 ng/mL), deficiency (<20 ng/mL)]. Data on delirium incidence, mortality, invasive mechanical ventilation (IMV) requirement during treatment, length of ICU and hospital admission, and re-hospitalization were recorded until 45 days after the baseline.ResultsVitamin D deficiency and insufficiency were prevalent among 12 % and 37 % of study participants, respectively. In terms of baseline differences, patients with vitamin D deficiency were more likely to be older, have organ failure, take propofol, need IMV, and were less likely to need face mask compared to patients with normal levels of vitamin D. A significant positive association was found between vitamin D deficiency and risk of delirium. After controlling for potential confounders, patients with vitamin D deficiency had a 54 % higher risk of delirium compared to those with vitamin D sufficiency (HR: 1.54, 95 % CI: 1.02–2.33). Such a positive association was also seen for 45-day COVID-19 mortality (HR: 3.95, 95 % CI: 1.80–8.67). Also, each 10 ng/mL increase in vitamin D levels was associated with a 45 % and 26 % lower risk of 45-day mortality (HR: 0.55, 95 % CI: 0.40–0.74) and ICU mortality due to COVID-19 (HR: 0.74, 95 % CI: 0.60–0.92), respectively. In terms of other COVID-19 outcomes including IMV requirement during treatment, prolonged hospitalization, and re-hospitalization, we found no significant association in relation to serum 25(OH)D3 levels either in crude or fully adjusted models.ConclusionVitamin D deficiency was associated with an increased risk of delirium and mortality among critically ill elderly COVID-19 patients.     

A comparative analysis of the outcomes of patients with influenza or COVID-19 in a tertiary hospital in Belgium

IntroductionThe COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium.MethodsIn this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO.ResultsBased on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: ?0.10, 95% CI: 0.15 to ?0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%).ConclusionsCOVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.     

Diabetes mellitus,glycaemic control,and severe COVID-19 in the Australian critical care setting: A nested cohort study

BackgroundInternationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population.ObjectiveThe objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19.MethodsThis is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression.ResultsThere were 136 patients with median age 58 years [48–68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11–19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia.ConclusionDiabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.     

Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records–based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare–affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59–0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47–0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997–0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare–affiliated entity, including Sarah Cannon and Genospace.     

Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis

BackgroundIn this systematic review and meta-analysis, we aimed to investigate the correlation of D-dimer levels measured on admission with disease severity and the risk of death in patients with coronavirus disease 2019 (COVID-19) pneumonia.Materials and methodsWe performed a comprehensive literature search from several databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). D-dimer levels were pooled and compared between severe/non-severe and surviving/non-surviving patient groups. Weighted mean difference (WMD), risk ratios (RRs) and 95% confidence intervals (CIs) were analyzed.ResultsThirty-nine studies reported on D-dimer levels in 5750 non-severe and 2063 severe patients and 16 studies reported on D-dimer levels in 2783 surviving and 697 non-surviving cases. D-dimer levels were significantly higher in patients with severe clinical status (WMD: 0.45 mg/L, 95% CI: 0.34–0.56; p < 0.0001). Non-surviving patients had significantly higher D-dimer levels compared to surviving patients (WMD: 5.32 mg/L, 95% CI: 3.90–6.73; p < 0.0001). D-dimer levels above the upper limit of normal (ULN) was associated with higher risk of severity (RR: 1.58, 95% CI: 1.25–2.00; p < 0.0001) and mortality (RR: 1.82, 95% CI: 1.40–2.37; p < 0.0001).ConclusionIncreased levels of D-dimer levels measured on admission are significantly correlated with the severity of COVID-19 pneumonia and may predict mortality in hospitalized patients.     

Computed tomography severity score as a predictor of disease severity and mortality in COVID-19 patients: A systematic review and meta-analysis

BackgroundPrediction of outcomes in severe COVID-19 patients using chest computed tomography severity score (CTSS) may enable more effective clinical management and early, timely ICU admission. We conducted a systematic review and meta-analysis to determine the predictive accuracy of the CTSS for disease severity and mortality in severe COVID-19 subjects.MethodsThe electronic databases PubMed, Google Scholar, Web of Science, and the Cochrane Library were searched to find eligible studies that investigated the impact of CTSS on disease severity and mortality in COVID-19 patients between 7 January 2020 and 15 June 2021. Two independent authors looked into the risk of bias using the Quality in Prognosis Studies (QUIPS) tool.ResultsSeventeen studies involving 2788 patients reported the predictive value of CTSS for disease severity. The pooled sensitivity, specificity, and summary area under the curve (sAUC) of CTSS were 0.85 (95% CI 0.78–0.90, I² =83), 0.86 (95% CI 0.76–0.92, I² =96) and 0.91 (95% CI 0.89–0.94), respectively. Six studies involving 1403 patients reported the predictive values of CTSS for COVID-19 mortality. The pooled sensitivity, specificity, and sAUC of CTSS were 0.77 (95% CI 0.69–0.83, I² = 41), 0.79 (95% CI 0.72–0.85, I² = 88), and 0.84 (95% CI 0.81–0.87), respectively.DiscussionEarly prediction of prognosis is needed to deliver the better care to patients and stratify them as soon as possible. Because different CTSS thresholds have been reported in various studies, clinicians are still determining whether CTSS thresholds should be used to define disease severity and predict prognosis.ConclusionEarly prediction of prognosis is needed to deliver optimal care and timely stratification of patients.  CTSS has strong discriminating power for the prediction of disease severity and mortality in patients with COVID-19.     

Diagnostic significance of secondary bacteremia in patients with COVID-19

ObjectivesWe investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsThis was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections.ResultsOf the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97–39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia.ConclusionsSecondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.     

The effect of cardiovascular disease and acute cardiac injury on fatal COVID-19: a meta-analysis

BackgroundWith the continuance of the global COVID-19 pandemic, cardiovascular disease (CVD) and cardiac injury have been suggested to be risk factors for severe COVID-19.ObjectiveThe aim is to evaluate the mortality risks associated with CVD and cardiac injury among hospitalized COVID-19 patients, especially in subgroups of populations in different countries.MethodsA comprehensive systematic literature search was performed using 9 databases from November 1, 2019 to November 9, 2020. Meta-analyses were performed for CVD and cardiac injury between non-survivors and survivors of COVID-19.ResultsAlthough the prevalence of CVD in different populations was different, hospitalized COVID-19 patients with CVD were at a higher risk of fatal outcomes (OR = 2.72; 95% CI 2.35–3.16) than those without CVD. Separate meta-analyses of populations in four different countries also reached a similar conclusion that CVD was associated with an increase in mortality. Cardiac injury was common among hospitalized COVID-19 patients. Patients with cardiac injury had a significantly higher mortality risk than those without cardiac injury (OR = 13.25; 95% CI: 8.56–20.52).ConclusionsPatients' CVD history and biomarkers of cardiac injury should be taken into consideration during the hospital stay and incorporated into the routine laboratory panel for COVID-19.