While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin-converting enzyme 2 receptor and initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. To establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (control: 5 M/15 F, 23.0 ± 1.3 y, 167 ± 9 cm, 63.0 ± 7.4 kg) and young adults who, 3–4 wk prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4 M/7 F, 20.2 ± 1.1 y, 172 ± 12 cm, 69.5 ± 12.4 kg) (means ± SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Carotid-femoral pulse wave velocity (PWVcf) was asvsessed as a marker of arterial stiffness. FMD was lower in the SARS-CoV-2 group (2.71 ± 1.21%) compared with the control group (8.81 ± 2.96%) (P < 0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04 ± 0.02 AU, control: 0.13 ± 0.06 AU, P < 0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (−3 ± 91 mL) compared with the control group (118 ± 114 mL) (P < 0.01). PWVcf was higher in the SARS-CoV-2 group (5.83 ± 0.62 m/s) compared with the control group (5.17 ± 0.66 m/s) (P < 0.01). Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared with controls. NEW & NOTEWORTHY This study was the first to investigate the vascular implications of contracting SARS-CoV-2 among young, otherwise healthy adults. Using a cross-sectional design, this study assessed vascular function 3–4 wk after young adults tested positive for SARS-CoV-2. The main findings from this study were a strikingly lower vascular function and a higher arterial stiffness compared with healthy controls. Together, these results suggest rampant vascular effects seen weeks after contracting SARS-CoV-2 in young adults.

Key points: The impact of SARS‐CoV‐2 infection on autonomic and cardiovascular function in otherwise healthy individuals is unknown. For the first time it is shown that young adults recovering from SARS‐CoV‐2 have elevated resting sympathetic activity, but similar heart rate and blood pressure, compared with control subjects. Survivors of SARS‐CoV‐2 also exhibit similar sympathetic nerve activity and haemodynamics, but decreased pain perception, during a cold pressor test compared with healthy controls. Further, these individuals display higher sympathetic nerve activity throughout an orthostatic challenge, as well as an exaggerated heart rate response to orthostasis. If similar autonomic dysregulation, like that found here in young individuals, is present in older adults following SARS‐CoV‐2 infection, there may be substantial adverse implications for cardiovascular health. The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can elicit systemic adverse physiological effects. However, the impact of SARS‐CoV‐2 on autonomic and cardiovascular function in otherwise healthy individuals remains unclear. Young adults who tested positive for SARS‐CoV‐2 (COV+; n = 16, 8 F) visited the laboratory 35 ± 16 days following diagnosis. Muscle sympathetic nerve activity (MSNA), systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were measured in participants at rest and during a 2 min cold pressor test (CPT) and 5 min each at 30° and 60° head‐up tilt (HUT). Data were compared with age‐matched healthy controls (CON; n = 14, 9 F). COV+ participants (18.2 ± 6.6 bursts min⁻¹) had higher resting MSNA burst frequency compared with CON (12.7 ± 3.4 bursts min⁻¹) (P = 0.020), as well as higher MSNA burst incidence and total activity. Resting HR, SBP and DBP were not different. During CPT, there were no differences in MSNA, HR, SBP or DBP between groups. COV+ participants reported less pain during the CPT compared with CON (5.7 ± 1.8 vs. 7.2 ± 1.9 a.u., P = 0.036). MSNA was higher in COV+ compared with CON during HUT. There was a group‐by‐position interaction in MSNA burst incidence, as well as HR, in response to HUT. These results indicate resting sympathetic activity, but not HR or BP, may be elevated following SARS‐CoV‐2 infection. Further, cardiovascular and perceptual responses to physiological stress may be altered, including both exaggerated (orthostasis) and suppressed (pain perception) responses, compared with healthy young adults.

New Findings: What is the central question of this study? We sought to investigate whether carotid stiffness, carotid intima–media thickness and the aortic augmentation index are altered in young adults 3–4 weeks after contraction of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) compared with young healthy adults. What is the main finding and its importance? We found that carotid stiffness, Young's modulus and the aortic augmentation index were greater in young adults who tested positive for SARS‐CoV‐2 compared with healthy young adults. These findings provide additional evidence for detrimental effects of SARS‐CoV‐2 on young adult vasculature, which might have implications for cardiovascular health. Contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been observed to cause decrements in vascular function of young adults. However, less is known about the impact of SARS‐CoV‐2 on arterial stiffness and structure, which might have additional implications for cardiovascular health. The purpose of this study was to assess the carotid artery stiffness and structure using ultrasound and the aortic augmentation index (AIx) using applanation tonometry in young adults after they tested positive for SARS‐CoV‐2. We hypothesized that carotid artery stiffness, carotid intima–media thickness (cIMT) and aortic AIx would be elevated in young adults with SARS‐CoV‐2 compared with healthy young adults. We evaluated 15 young adults (six male and nine female; 20 ± 1 years of age; body mass index, 24 ± 3 kg m⁻²) 3–4 weeks after a positive SARS‐CoV‐2 test result compared with young healthy adults (five male and 10 female; 23 ± 1 years of age; body mass index, 22 ± 2 kg m⁻²) who were evaluated before the coronavirus 2019 pandemic. Carotid stiffness, Young's modulus and cIMT were assessed using ultrasound, whereas aortic AIx and aortic AIx standardized to 75 beats min⁻¹ (AIx@HR75) were assessed from carotid pulse wave analysis using SphygmoCor. Group differences were observed for carotid stiffness (control, 5 ± 1 m s⁻¹; SARS‐CoV‐2, 6 ± 1 m s⁻¹), Young's modulus (control, 396 ± 120 kPa; SARS‐CoV‐2, 576 ± 224 kPa), aortic AIx (control, 3 ± 13%; SARS‐CoV‐2, 13 ± 9%) and aortic AIx@HR75 (control, −3 ± 16%; SARS‐CoV‐2, 10 ± 7%; P < 0.05). However, cIMT was similar between groups (control, 0.42 ± 0.06 mm; SARS‐CoV‐2, 0.44 ± 0.08 mm; P > 0.05). This cross‐sectional analysis revealed higher carotid artery stiffness and aortic stiffness among young adults with SARS‐CoV‐2. These results provide further evidence of cardiovascular impairments among young adults recovering from SARS‐CoV‐2 infection, which should be considered for cardiovascular complications associated with SARS‐CoV‐2.

Common cyclooxygenase (COX)-inhibiting drugs enhance resistance exercise induced muscle mass and strength gains in older individuals. The purpose of this investigation was to determine whether the underlying mechanism regulating this effect was specific to Type I or Type II muscle fibers, which have different contractile and metabolic profiles. Muscle biopsies (vastus lateralis) were obtained before and after 12 weeks of knee-extensor resistance exercise (3 days/week) from healthy older men who consumed either a placebo ( n = 8; 64±2 years) or COX inhibitor (acetaminophen, 4 gram/day; n = 7; 64±1 years) in double-blind fashion. Muscle samples were examined for Type I and II fiber cross-sectional area, capillarization, and metabolic enzyme activities (glycogen phosphorylase, citrate synthase, β-hydroxyacyl-CoA-dehydrogenase). Type I fiber size did not change with training in the placebo group (304±590 μm ² ) but increased 28% in the COX inhibitor group (1,388±760 μm ² , p < .1). Type II fiber size increased 26% in the placebo group (1,432±499 μm ² , p < .05) and 37% in the COX inhibitor group (1,825±400 μm ² , p < .05). Muscle capillarization and enzyme activity were generally maintained in the placebo group. However, capillary to fiber ratio increased 24% ( p < .1) and citrate synthase activity increased 18% ( p < .05) in the COX inhibitor group. COX inhibitor consumption during resistance exercise in older individuals enhances myocellular growth, and this effect is more pronounced in Type I muscle fibers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase arterial stiffness 3–4 wk following infection, even among young, healthy adults. However, the long-term impacts of SARS-CoV-2 infection on cardiovascular health and the duration of recovery remain unknown. The purpose of this study was to elucidate potential long-lasting effects of SARS-CoV-2 infection on markers of arterial stiffness among young adults during the 6 mo following infection. Assessments were performed at months 1, 2, 3, 4, and ∼6 following SARS-CoV-2 infection. Doppler ultrasound was used to measure carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness, and arterial tonometry was used to measure central blood pressures and aortic augmentation index at a heart rate of 75 beats·min⁻¹ ([email protected]). Vascular (VCAM-1) and intracellular (ICAM-1) adhesion molecules were analyzed as circulating markers of arterial stiffness. From months 1–6, a significant reduction in cfPWV was observed (month 1: 5.70 ± 0.73 m·s⁻¹; month 6: 4.88 ± 0.65 m·s⁻¹; P < 0.05) without any change in carotid stiffness measures. Reductions in systolic blood pressure (month 1: 123 ± 8 mmHg; month 6: 112 ± 11 mmHg) and mean arterial pressure (MAP; month 1: 97 ± 6 mmHg; month 6: 86 ± 7 mmHg) were observed (P < 0.05), although [email protected] did not change over time. The month 1–6 change in cfPWV and MAP were correlated (r = 0.894; P < 0.001). A reduction in VCAM-1 was observed at month 3 compared with month 1 (month 1: 5,575 ± 2,242 pg·mL⁻¹; month 3: 4,636 ± 1,621 pg·mL⁻¹; P < 0.05) without a change in ICAM-1. A reduction in cfPWV was related with MAP, and some indicators of arterial stiffness remain elevated for several months following SARS-CoV-2 infection, possibly contributing to prolonged recovery and increased cardiovascular health risks. NEW & NOTEWORTHY We sought to investigate potential long-lasting effects of SARS-CoV-2 infection on markers of arterial stiffness among young adults for 6 mo following infection. Carotid femoral pulse wave velocity was significantly reduced while carotid stiffness measures remained unaltered over the 6-mo period. These findings suggest several months of recovery from infection may be necessary for young adults to improve various markers of arterial stiffness, possibly contributing to cardiovascular health and recovery among those infected with SARS-CoV-2.

The Prospective comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and morbidity in Heart Failure trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan (trade name Entresto), but the physiological processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF (n = 11, 10 M/1 F, left ventricular ejection fraction = 27 ± 8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function [brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)], functional capacity [six-minute walk test (6MWT) distance], and the proinflammatory biomarkers tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and at 1, 2, and 3 mo of treatment. %FMD improved after 1 mo of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25 ± 1.75%; 1 mo: 5.23 ± 2.36%; 2 mo: 5.81 ± 1.79%; 3 mo: 6.35 ± 2.77%), whereas RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420 ± 92 m; 1 mo: 436 ± 98 m; 2 mo: 465 ± 115 m; 3 mo: 460 ± 110 m), and there was a sustained reduction in TNF-α (baseline: 2.38 ± 1.35 pg/mL; 1 mo: 2.06 ± 1.52 pg/mL; 2 mo: 1.95 ± 1.34 pg/mL; 3 mo: 1.92 ± 1.37 pg/mL) and a reduction in IL-18 at month 3 (baseline: 654 ± 150 pg/mL; 1 mo: 595 ± 140 pg/mL; 2 mo: 601 ± 176 pg/mL; 3 mo: 571 ± 127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF. NEW & NOTEWORTHY We observed an approximately twofold improvement in conduit vessel function (brachial artery FMD), increased functional capacity (6MWT distance), and a reduction in inflammation (TNF-α and IL-18) following 3 mo of sacubitril-valsartan therapy. These findings provide important new information concerning the physiological mechanisms by which this new drug class provokes favorable changes in HFrEF pathophysiology.