Cardiovascular biomarkers among patients with and without persistent symptoms weeks after COVID-19 infection

Introduction

Following COVID-19 infection, some patients develop "Long COVID" with symptoms that persist or develop weeks after the initial infection. The precise mechanisms leading to Long COVID remain uncertain, and it is unclear why some individuals have complete recovery from acute COVID-19 infection while others develop longer-term symptoms. Given the potential for COVID-19 to trigger both short- and long-term cardiac complications, it is plausible that occult cardiac involvement could be a key mechanism underlying Long COVID symptoms

Purpose

To compare the baseline and longitudinal cardiovascular biomarker signatures of patients with and without persistent symptoms weeks after acute COVID-19 infection.

Methods

PARACOR-19 was a single-center randomized trial of 42 patients with a history of COVID-19 infection 4-16 weeks prior to enrollment. Patients were randomized to sacubitril/valsartan versus placebo, with no significant differences in co-primary endpoints of change in high-sensitivity troponin T and soluble ST2. The current post-hoc analysis compared the clinical characteristics and longitudinal changes in 9 cardiovascular biomarkers for patients with and without residual COVID-19 symptoms at study baseline. Changes in cardiovascular biomarker levels from baseline to 12 weeks were compared between groups using least squares means estimates.

Results

At baseline, 18 (42.9%) patients reported persistent COVID-19 symptoms, and 24 (57.1%) patients did not. Among those with persistent symptoms, the most common symptom was severe fatigue (38.9%), followed by cough, shortness of breath, or altered taste/smell (27.8% each). Median time from positive COVID-test to study enrollment was 67 days (Q1-Q3: 54-88) and 66 days (Q1-Q3: 46.5-81.5) for those with and without persistent symptoms, respectively.

Overall, median age was 67 years (Q1-Q3: 62-71), 22 (52.4%) were men, and 38 (90.5%) were White. In comparing patients with and without persistent symptoms, there were no statistically significant differences in demographics or key comorbidities (Table). Patients with persistent had higher baseline systolic blood pressure, worse EQ-5D health status, and were less likely to have previously received the COVID-19 vaccine. There were no significant differences in baseline cardiovascular biomarkers (Table). Over 12-week follow-up, there were no significant differences in the change in cardiovascular biomarkers for those with versus without persistent COVID-19 symptoms (Figure).

Discussion

Among patients with a history of COVID-19 infection in the past 4-16 weeks, more than 4 in 10 patients reported persistent symptoms. There were no significant differences in baseline or longitudinal cardiovascular biomarkers among patients with and without persistent COVID-19 symptoms. Further research is needed to understand the biologic factors that distinguish those with persistent symptoms from those with early complete recovery from COVID-19.Baseline Patient CharacteristicsFor image description, please refer to the figure legend and surrounding text.Changes in Cardiovascular BiomarkersFor image description, please refer to the figure legend and surrounding text.