Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study.

Background: COVID-19 is associated with subclinical myocardial injury. Exogenous ketone esters acutely improve left myocardial function in healthy participants and patients with heart failure, but the effects have not been investigated in participants previously hospitalized for COVID-19. Methods: This is a randomized placebo-controlled double-blind crossover study comparing a single oral ketone ester dose of 395 mg/kg with placebo. Fasting participants were randomized to either placebo in the morning and oral ketone ester in the afternoon or vice versa. Echocardiography was performed immediately after intake of the corresponding treatment. Primary outcome was left ventricular ejection fraction (LVEF). Secondary outcomes were absolute global longitudinal strain (GLS), cardiac output and blood oxygen saturation. Linear mixed effects models were used to assess differences. Results: We included 12 participants previously hospitalized for COVID-19 with a mean (±SD) age of 60 ± 10 years. The mean time from hospitalization was 18 ± 5 months. Oral ketone esters did not increase LVEF between placebo and oral ketone ester [mean difference: -0.7% (95% CI -4.0 to 2.6%), p = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), p = 0.04] and cardiac output [1.2 L/min (95% CI: -0.1 to 2.4 L/min), p = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate (p = 0.01). There was no difference in blood oxygen saturation. Oral ketone esters increased blood ketones over time (peak level 3.1 ± 4.9 mmol/L, p < 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all p ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all p > 0.05). Conclusion: In patients previously hospitalized with COVID-19, a single oral dose of ketone ester had no effect on LVEF, cardiac output or blood oxygen saturation, but increased GLS acutely. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04377035.

Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study.

INTRODUCTION: COVID-19 has spread globally in waves, and Danish treatment guidelines have been updated following the first wave. We sought to investigate whether the prognostic values of echocardiographic parameters changed with updates in treatment guidelines and the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, 20E (EU1) and Alpha (B.1.1.7), and further to compare cardiac parameters between patients from the first and second wave. METHODS: A total of 305 patients hospitalised with COVID-19 were prospectively included, 215 and 90 during the first and second wave, respectively. Treatment in the study was defined as treatment with remdesivir, dexamethasone, or both. Patients were assumed to be infected with the dominant SARS-CoV-2 variant at the time of their hospitalisation. RESULTS: Mean age for the first vs. second wave was 68.7±13.6 vs. 69.7±15.8 years and 55% vs. 62% were male. Left ventricular (LV) systolic and diastolic function was worse in patients hospitalised during the second wave (LV ejection fraction (LVEF) for first vs. second wave = 58.5±8.1% vs. 52.4±10.6%, p<0.001) and global longitudinal strain (GLS) = 16.4±4.3% vs. 14.2±4.3%, p<0.001). In univariable cox regressions, reduced LVEF (HR=1.07 per 1% decrease, p=0.002), GLS (HR=1.21 per 1% decrease, p<0.001), and TAPSE (HR=1.18 per 1mm decrease, p<0.001) were associated with covid-related mortality, but only GLS remained significant in fully adjusted analysis (HR=1.14, p=0.02). CONCLUSION: Reduced GLS was associated with covid-related mortality independently of wave, treatment, and SARS-CoV-2 variant. LV function was significantly impaired in patients hospitalised during the second wave.

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for diagnosis and monitoring in patients with active COVID-19-infection. However, less is known about the changes in LUS findings after a hospitalization for COVID-19. METHODS: In a prospective, longitudinal study in patients with COVID-19 enrolled from non-ICU hospital units, adult patients underwent 8-zone LUS and blood sampling both during the hospitalization and 2-3 months after discharge. LUS images were analyzed blinded to clinical variables and outcomes. RESULTS: A total of 71 patients with interpretable LUS at baseline and follow up (mean age 64 years, 61% male, 24% with acute respiratory distress syndrome (ARDS)) were included. The follow-up LUS was performed a median of 72 days after the initial LUS performed during hospitalization. At baseline, 87% had pathologic LUS findings in ≥1 zone (e.g. ≥3 B-lines, confluent B-lines or subpleural or lobar consolidation), whereas 30% had pathologic findings at follow-up (p < 0.001). The total number of B-lines and LUS score decreased significantly from hospitalization to follow-up (median 17 vs. 4, p < 0.001 and 4 vs. 0, p < 0.001, respectively). On the follow-up LUS, 28% of all patients had ≥3 B-lines in ≥1 zone, whereas in those with ARDS during the baseline hospitalization (n = 17), 47% had ≥3 B-lines in ≥1 zone. CONCLUSION: LUS findings improved significantly from hospitalization to follow-up 2-3 months after discharge in COVID-19 survivors. However, persistent B-lines were frequent at follow-up, especially among those who initially had ARDS. LUS seems to be a promising method to monitor COVID-19 lung changes over time. GOV ID: NCT04377035.

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.