Types of myocardial injury and mid-term outcomes in patients with COVID-19.

AIMS: To evaluate the acute and chronic patterns of myocardial injury among patients with coronavirus disease-2019 (COVID-19), and their mid-term outcomes. METHODS AND RESULTS: Patients with laboratory-confirmed COVID-19 who had a hospital encounter within the Mount Sinai Health System (New York City) between 27 February 2020 and 15 October 2020 were evaluated for inclusion. Troponin levels assessed between 72 h before and 48 h after the COVID-19 diagnosis were used to stratify the study population by the presence of acute and chronic myocardial injury, as defined by the Fourth Universal Definition of Myocardial Infarction. Among 4695 patients, those with chronic myocardial injury (n = 319, 6.8%) had more comorbidities, including chronic kidney disease and heart failure, while acute myocardial injury (n = 1168, 24.9%) was more associated with increased levels of inflammatory markers. Both types of myocardial injury were strongly associated with impaired survival at 6 months [chronic: hazard ratio (HR) 4.17, 95% confidence interval (CI) 3.44-5.06; acute: HR 4.72, 95% CI 4.14-5.36], even after excluding events occurring in the first 30 days (chronic: HR 3.97, 95% CI 2.15-7.33; acute: HR 4.13, 95% CI 2.75-6.21). The mortality risk was not significantly different in patients with acute as compared with chronic myocardial injury (HR 1.13, 95% CI 0.94-1.36), except for a worse prognostic impact of acute myocardial injury in patients <65 years of age (P-interaction = 0.043) and in those without coronary artery disease (P-interaction = 0.041). CONCLUSION: Chronic and acute myocardial injury represent two distinctive patterns of cardiac involvement among COVID-19 patients. While both types of myocardial injury are associated with impaired survival at 6 months, mortality rates peak in the early phase of the infection but remain elevated even beyond 30 days during the convalescent phase.

Characterization of Myocardial Injury in Patients With COVID-19.

BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Targeted, Site-Specific, Delivery Vehicles of Therapeutics for COVID-19 Patients. Brief Review.

Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.