Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. Results: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO₂ consumption (77.8 (64–92.5) vs. 99 (88–105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467–600) vs. 611 (550–650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VC_O2 slope 32 (28.1–37.4) vs. 29.4 (26.9–31.4); p = 0.022) and high PET_CO2 (34.5 (32–39) vs. 38 (36–40); p = 0.025). Interpretation: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969–0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998–0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017–1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433–0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010–1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Background: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin‐angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation. Methods and Results: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1‐year follow‐up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79–86), 58.1% women, and EuroSCORE‐II 3.75% (range 3.08–4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in‐hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group ( P =0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P =0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P =0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end‐systolic and end‐diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis. Conclusions: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re‐admissions at 1‐year follow‐up. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03201185.

Background (1): Headache is a prevalent symptom experienced during ongoing SARS-CoV-2 infection, but also weeks after recovery. Whether cardio-pulmonary dysfunction contributes causally to headache persistence is unknown. Methods (2): We conducted a case-control analysis nested in a prospective cohort study. Individuals were recruited from August 2020 to December 2020. Patients were grouped according to the presence or absence of long-COVID headache for three months after COVID-19 resolution. We compared demographic data, clinical variables, cardio-pulmonary laboratory biomarkers, quality of life, and cardio-pulmonary function between groups. Results (3): A cohort of 70 COVID-19 patients was evaluated. Patients with headaches (n = 10; 14.3%) were more frequently female (100% vs. 58.4%; p = 0.011) and younger (46.9 ± 8.45 vs. 56.13 ± 12 years; p = 0.023). No between-group differences in laboratory analysis, resting echocardiography, cardio-pulmonary exercise test, or pulmonary function tests were observed. Conclusion (4): In this exploratory study, no significant differences in cardio-pulmonary dysfunction were observed between patients with and without long-COVID headache during mid-term follow-up.