Platelet activation and COVID-19 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation

Background: Severe coronavirus disease 2019 (COVID-19) is associated with inflammatory cytokine burst and coagulopathy. Platelets may contribute to microthrombosis development and be a target in COVID-19 therapy. Aim(s): To determine the significance of platelet activation and antiplatelet agents (APAs) treatment in COVID-19 pathophysiology and mortality in two cohorts of patients with COVID-19. Method(s): We explored two cohorts of COVID-19 patients: Cohort A (NCT04624997) included 208 ambulatory and hospitalized patients of different clinical severity with evaluation of soluble CD40 ligand (sCD40L) and P-selectin (sP-sel) plasma levels of within the first 48 hours following admission. Cohort B included 2878 patients initially admitted in medical ward with collection of clinical characteristics and outcomes (NCT04344327). In both cohorts, the primary outcome was in-hospital mortality. Result(s): In cohort A, circulating median levels of sCD40L and sP-sel were significantly increased solely in critical patients with COVID-19 (sP-sel: 40059 pg/ml, IQR 26876-54678;sCD40L: 1914 pg/ml IQR 1410-2367;p < 0.001 for both), signaling platelet hyper-activation. However, pre-hospitalization APAs did not significantly modified sCD40L and sP-sel levels. Admission sP-sel levels were predictive in-hospital mortality (Kaplan-Meier log-rank p = 0.004), even after adjustment on CRP, while adjustment on D-dimer abolished this relationship, suggesting that platelet activation is highly interrelated with coagulopathy. We confirmed this finding in a Cox model adjusted for age, sex, CRP and D-dimer levels (Odds ratio 1.78, 95% CI 0.63-4.50). We confirmed in cohort B (2878 patients) that, among patients receiving APA before hospitalization, there was no significant difference in the proportion of death in a Cox model (Hazard ratio 1.0, IQR0.77-1.30) adjusted for demographic comorbidities. Conclusion(s): Our findings highlight the critical role of coagulopathy, in contrast to platelet activation, in discriminating COVID-19 severity and increased risk of in-hospital mortality. We also confirm that APAs before hospitalization do not influence neither mortality nor platelet activation. (Table Presented).

Cardiovascular manifestations secondary to COVID-19: A narrative review.

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly, becoming a major threat to global health. In addition to having required the adaptation of healthcare workers for almost 2 years, it has been much talked about, both in the media and among the scientific community. Beyond lung damage and respiratory symptoms, the involvement of the cardiovascular system largely explains COVID-19 morbimortality. In this review, we emphasize that cardiovascular involvement is common and is associated with a worse prognosis, and that earlier detection by physicians should lead to better management. First, direct cardiac involvement will be discussed, in the form of COVID-19 myocarditis, then secondary cardiac involvement, such as myocardial injury, myocardial infarction and arrhythmias, will be considered. Finally, worsening of previous cardiovascular disease as a result of COVID-19 will be examined, as well as long-term COVID-19 effects and cardiovascular complications of COVID-19 vaccines.

COVID-19 in young patients: Less cardiovascular risk factors but more specific cardiovascular complications

Background Main features of COVID-19 patients have been reported in the literature. While young patients under 45 years old (y/o) account for a non-negligible part of hospitalized patients, data on this population remain sparse. Purpose To describe the characteristics and outcomes of hospitalized COVID-19 young patients (< 45 y/o). Methods The Critical COVID France (CCF) study was an observational multicenter study including patients hospitalized for COVID-19. Primary composite outcome included transfer to ICU or in-hospital death. Secondary outcomes were cardiovascular complications diagnosed by the referring medical team according to available clinical, biological and radiological findings. Results Among 2,878 patients hospitalized for COVID-19 in 24 centers, 321 (11.2%) patients were under the age of 45 y/o. They had a higher body mass index (BMI) (28.9 ± 6.6 vs 27.7 ± 6.0, P = 0.004) but less other cardiovascular risk factors including hypertension (29 (9.2%) vs. 1422 (56.1%), P < 0.001), diabetes (20 (6.3%) vs. 656 (25.9%), P < 0.001) and dyslipidemia (15 (4.7%) vs. 783 (30.7%), P < 0.001). The primary outcome occurred in 54 (16.8%) patients under 45 y/o vs. 783 (30.7%) in patients aged > 45 y/o (P < 0.001), with a strong impact on the death rate (3 (0.9%) vs. 358 (14.0%), P < 0.001). The group under 45 y/o experienced more frequently related COVID-19 cardiovascular complications such as pericarditis (12 (0.5%) vs. 7 (2.2%), P = 0.003) and myocarditis (14 (0.6%) vs 8 (2.5%), P = 0.002). Conversely, acute heart failure occurred more frequently in patients aged > 45 y/o (183 (7.2%) vs. 3 (0.9%), P < 0.001). Acute coronary syndrome and stroke were similar between the two groups (Fig. 1). Conclusion In this nationwide multicenter observational study of hospitalized COVID-19 patients, patients under the age of 45 y/o had less cardiovascular risk factors but more specific related COVID-19 cardiovascular complications such as pericarditis and myocarditis.

Cardiovascular Comorbidities and Covid-19 in Women

Background: While women account for 40-50 % of patients hospitalized for coronavirus disease 2019 (Covid-19), no specific data have been reported in this population. Purpose: Assess the burden of cardiovascular comorbidities on outcomes in women hospitalized for Covid-19. Methods: We conducted a retrospective observational multicenter study from February 26 to April 20, 2020 in 24 French hospitals including all adults admitted for Covid-19. Primary composite outcome included transfer to intensive care unit (ICU) or in-hospital death. Results: Among 2878 patients hospitalized for Covid-19, 1212 (42.1 %) were women. Women were significantly older (68.3 ± 18.0 vs. 65.4 ± 16.0 years, P < 0.001) but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8 %) experienced the primary outcome, including 161 (13.3 %) transfer to ICU and 115 (9.5 %) deaths without transfer to ICU. The survival free from death or transfer to ICU was higher in women (HR 0.63, 95 %CI 0.53-0.73, P < 0.001), whereas the observed difference in in-hospital deaths did not reach statistical significance (P = 0.18). The proportion of women that experienced the primary outcome were 37.8 % in women with heart failure (n = 112), 30.9 % in women with coronary artery disease (n = 81), 29.1 % in women with diabetes (n = 254), 26.1 % in women with dyslipidemia (n = 315), and 26.0 % in women with hypertension (n = 632). Age (HR 1.05, 5 years increments, 95 %CI 1.01-1.10), body mass index (HR 1.06, 2 units increments, 95 %CI 1.02-1.10), chronic kidney disease (HR 1.57, 95 %CI 1.11-2.22), and heart failure (HR 1.52, 95 %CI 1.04-2.22) were independently associated with the primary outcome (Fig. 1). Conclusions: Women hospitalized for Covid-19 were older and had less prevalent cardiovascular comorbidities than men. While female sex was associated with a lower risk of transfer to ICU or in-hospital death, Covid-19 remains associated with considerable morbi-mortality in women, especially in those with cardiovascular diseases.

Pulmonary Embolism in Covid-19 patients: A French Multicentre Cohort Study

Background: While pulmonary embolism (PE) appears to be a major issue in Covid-19, data remain sparse. Purpose: We aimed to describe the risk factors and baseline characteristics of patients with PE in a large cohort of Covid-19 patients. Methods: In a retrospective multicentric observational study, we included consecutive hospitalised patients for Covid-19. Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis, those who were directly admitted to an intensive care unit (ICU), and those still hospitalised without PE experience were excluded. Results: Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA. The ICU transfer requirement and mechanical ventilation requirement were significantly higher in the PE group (P < 0.001 and P < 0.001, respectively). In an univariable analysis, traditional venous thromboembolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic-dose anticoagulation before hospitalisation or prophylaxis-dose anticoagulation introduced during hospitalisation had lower PE occurrence (OR 0.40, 95%CI(0.14-0.91);P = 0.04 and OR 0.11, 95%CI(0.06-0.18);P < 0.001, respectively). In a multivariable analysis, the following variables (also statistically significant in univariable analysis) were associated with PE: male gender (OR 1.03, 95%CI(1.003-1.069);P = 0.04), anticoagulation with prophylaxis-dose (OR 0.83, 95%CI(0.79-0.85), P < 0.001) or therapeutic-dose (OR 0.87, 95%CI(0.82-0.92), P < 0.001), C-reactive protein (OR 1.03, 95%CI(1.01-1.04), P = 0.001) and time from symptom onset to hospitalisation (OR 1.02, 95%CI(1.006-1.038), P = 0.002) (Table 1). Conclusion: Pulmonary embolism risk factors in Covid-19 context do not include traditional thromboembolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.