Cardiac Involvement in Recovered Patients From COVID-19: A Preliminary 6-Month Follow-Up Study.

Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients. Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed. Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro-B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement-negative subgroup. Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

High Systolic Blood Pressure at Hospital Admission Is an Important Risk Factor in Models Predicting Outcome of COVID-19 Patients.

BACKGROUND: The risk that coronavirus disease 2019 (COVID-19) patients develop critical illness that can be fatal depends on their age and immune status and may also be affected by comorbidities like hypertension. The goal of this study was to develop models that predict outcome using parameters collected at admission to the hospital. METHODS AND RESULTS: This is a retrospective single-center cohort study of COVID-19 patients at the Seventh Hospital of Wuhan City, China. Forty-three demographic, clinical, and laboratory parameters collected at admission plus discharge/death status, days from COVID-19 symptoms onset, and days of hospitalization were analyzed. From 157 patients, 120 were discharged and 37 died. Pearson correlations showed that hypertension and systolic blood pressure (SBP) were associated with death and respiratory distress parameters. A penalized logistic regression model efficiently predicts the probability of death with 13 of 43 variables. A regularized Cox regression model predicts the probability of survival with 7 of above 13 variables. SBP but not hypertension was a covariate in both mortality and survival prediction models. SBP was elevated in deceased compared with discharged COVID-19 patients. CONCLUSIONS: Using an unbiased approach, we developed models predicting outcome of COVID-19 patients based on data available at hospital admission. This can contribute to evidence-based risk prediction and appropriate decision-making at hospital triage to provide the most appropriate care and ensure the best patient outcome. High SBP, a cause of end-organ damage and an important comorbid factor, was identified as a covariate in both mortality and survival prediction models.

Association of Statin Use With the In-Hospital Outcomes of 2019-Coronavirus Disease Patients: A Retrospective Study.

Background: Statins have multiple protective effects on inflammation, immunity and coagulation, and may help alleviate pneumonia. However, there was no report focusing on the association of statin use with in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19). We investigated the association between the use of statins and in-hospital outcomes of patients with COVID-19. Methods: In this retrospective case series, consecutive COVID-19 patients admitted at 2 hospitals in Wuhan, China, from March 12, 2020 to April 14, 2020 were analyzed. A 1:1 matched cohort was created by propensity score-matched analysis. Demographic data, laboratory findings, comorbidities, treatments and in-hospital outcomes were collected and compared between COVID-19 patients taking and not taking statins. Result: A total of 2,147 patients with COVID-19 were enrolled in this study. Of which, 250 patients were on statin therapy. The mortality was 2.4% (6/250) for patients taking statins while 3.7% (70/1,897) for those not taking statins. In the multivariate Cox model, after adjusting for age, gender, admitted hospital, comorbidities, in-hospital medications and blood lipids, the risk was lower for mortality (adjusted HR, 0.428; 95% CI, 0.169-0.907; P = 0.029), acute respiratory distress syndrome (ARDS) (adjusted HR, 0.371; 95% CI, 0.180-0.772; P = 0.008) or intensive care unit (ICU) care (adjusted HR, 0.319; 95% CI, 0.270-0.945; P = 0.032) in the statin group vs. the non-statin group. After propensity score-matched analysis based on 18 potential confounders, a 1:1 matched cohort (206:206) was created. In the matched cohort, the Kaplan-Meier survival curves showed that the use of statins was associated with better survival (P = 0.025). In a Cox regression model, the use of statins was associated with lower risk of mortality (unadjusted HR, 0.254; 95% CI, 0.070-0.926; P = 0.038), development of ARDS (unadjusted HR, 0.240; 95% CI, 0.087-0.657; P = 0.006), and admission of ICU (unadjusted HR, 0.349; 95% CI, 0.150-0.813; P = 0.015). The results remained consistent when being adjusted for age, gender, total cholesterol, triglyceride, low density lipoprotein cholesterol, procalcitonin, and brain natriuretic peptide. The favorable outcomes in statin users remained statistically significant in the first sensitivity analysis with comorbid diabetes being excluded in matching and in the second sensitivity analysis with chronic obstructive pulmonary disease being added in matching. Conclusion: In this retrospective analysis, the use of statins in COVID-19 patients was associated with better clinical outcomes and is recommended to be continued in patients with COVID-19.

Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes.

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.

Angiotensin-converting enzyme 2: a double-edged sword in COVID-19 patients with an increased risk of heart failure.

The coronavirus disease (COVID-19) pandemic is a global health priority. Given that cardiovascular diseases (CVD) are the leading cause of morbidity around the world and that several trials have reported severe cardiovascular damage in patients infected with SARS-CoV-2, a substantial number of COVID-19 patients with underlying cardiovascular diseases need to continue their medications in order to improve myocardial contractility and to prevent the onset of major adverse cardiovascular events (MACEs), including heart failure. Some of the current life-saving medications may actually simultaneously expose patients to a higher risk of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2), a key counter regulator of the renin-angiotensin system (RAS), is the main entry gate of SARS-CoV-2 into human host cells and an established drug target to prevent heart failure. In fact, ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid antagonists may augment ACE2 levels to protect organs from angiotensin II overload. Elevated ACE2 expression on the host cell surface might facilitate viral entrance, at the same time sudden nonadherence to these medications triggers MACEs. Hence, safety issues in the use of RAS inhibitors in COVID-19 patients with cardiac dysfunction remain an unsolved dilemma and need paramount attention. Although ACE2 generally plays an adaptive role in both healthy subjects and patients with systolic and/or diastolic dysfunction, we conducted a literature appraisal on its maladaptive role. Understanding the exact role of ACE2 in COVID-19 patients at risk of heart failure is needed to safely manage RAS inhibitors in frail and non-frail critically ill patients.

Cardiac arrhythmias in patients with COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health concern. Although SARS-CoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. Cardiac arrhythmias are often observed in patients with COVID-19, especially in severe cases, and more likely contribute to the high risk of adverse outcomes. Arrhythmias should be regarded as one of the main complications of COVID-19. Mechanistically, a number of ion channels can be adversely affected in COVID-19, leading to alterations in cardiac conduction and/or repolarization properties, as well as calcium handling, which can predispose to cardiac arrhythmogenesis. In addition, several antimicrobials that are currently used as potential therapeutic agents for COVID-19, such as chloroquine, hydroxychloroquine and azithromycin, have uncertain benefit, and yet may induce electrocardiographic QT prolongation with potential ventricular pro-arrhythmic effects. Continuous electrocardiogram monitoring, accurate and prompt recognition of arrhythmias are important. The present review focuses on cardiac arrhythmias in patients with COVID-19, its underlying mechanisms, and proposed preventive and therapeutic strategies.

Clinical decision support tool and rapid point-of-care platform for determining disease severity in patients with COVID-19.

SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19).

Importance: Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. Objective: To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. Design, Setting, and Participants: This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. Main Outcomes and Measures: Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. Results: Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (ß = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (ß = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13). Conclusions and Relevance: Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.