Prognostic implications of serial high-sensitivity cardiac troponin testing among patients with COVID-19: A Danish nationwide registry-based cohort study.

Background: Although troponin elevation is associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19), prognostic implications of serial troponin testing are lacking. We investigated the association between serial troponin measurements and adverse COVID-19 outcomes. Methods: Using Danish registries, we identified COVID-19 patients with a high-sensitivity troponin measurement followed by a second measurement within 1-24 h. All measurements during follow-up were also utilized in subsequent time-varying analyses. We assessed all-cause mortality associated with the absence/presence of myocardial injury (≥1 troponin measurement >99th percentile upper reference limit) and absence/presence of dynamic troponin changes (>20% relative change if first measurement elevated, >50% relative change if first measurement normal). Results: Of 346 included COVID-19 patients, 56% had myocardial injury. Overall, 20% had dynamic troponin changes. In multivariable Cox regression models, myocardial injury was associated with all-cause mortality (HR = 2.56, 95%CI = 1.46-4.51), as were dynamic troponin changes (HR = 1.66, 95%CI = 1.04-2.64). We observed a low incidence of myocardial infarction (4%) and invasive coronary procedures (4%) among patients with myocardial injury. Conclusions: Myocardial injury and dynamic troponin changes determined using serial high-sensitivity troponin testing were associated with poor prognosis among patients with COVID-19. The risk of developing myocardial infarction requiring invasive management during COVID-19 hospitalization was low.

Glycated haemoglobin levels among 3295 hospitalized COVID-19 patients, with and without diabetes, and risk of severe infection, admission to an intensive care unit and all-cause mortality.

AIM: To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes. MATERIALS AND METHODS: Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported. RESULTS: We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference). CONCLUSIONS: Patients with COVID-19 and HbA1c < 48 mmol/mol or HbA1c > 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

OBJECTIVE: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19. DESIGN: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender. SETTING: All hospitals in Denmark. PARTICIPANTS: 1310 patients aged ≥18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data. MAIN OUTCOME MEASURES: A composite of death/ICU admission occurring within 30 days. RESULTS: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin. CONCLUSION: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days.

Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study.

Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), < 30 years (n = 575), and prescribed other nonsteroidal anti-inflammatory drugs (n = 57) were excluded. Patients with ibuprofen prescription claims between January 1, 2020, and before COVID-19 diagnosis or April 30, 2020 (last available prescription) were compared with patients without ibuprofen prescription claims. Outcome was a 30-day composite of severe COVID-19 diagnosis with acute respiratory syndrome, intensive care unit admission, or death. Absolute risks and average risk ratios comparing outcome for ibuprofen vs. non-ibuprofen patients standardized to the age, sex, and comorbidity distribution of all patients were derived from multivariable Cox regression. Among 4,002 patients, 264 (6.6%) had ibuprofen prescription claims before COVID-19. Age, sex, and comorbidities were comparable between the two study groups. Standardized absolute risks of the composite outcome for ibuprofen-prescribed vs. non-ibuprofen patients were 16.3% (95% confidence interval (CI) 12.1-20.6) vs. 17.0% (95% CI 16.0-18.1), P = 0.74. The standardized average risk ratio for ibuprofen-prescribed vs. non-ibuprofen patients was 0.96 (95% CI 0.72-1.23). Standardized absolute risks of the composite outcome for patients with ibuprofen prescription claims > 14 days before COVID-19 vs. ≤ 14 days of COVID-19 were 17.1% (95% CI 12.3-22.0) vs. 14.3% (95% CI 7.1-23.1). In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19.