The impact of COVID-19 has been largely described after symptom development. Although the SARS-CoV-2 virus elevates heart rate (HR) prior to symptom onset, whether this virus evokes other presymptomatic alterations is unknown. This Case Study details the presymptomatic impact of COVID-19 on vascular and skeletal muscle function in a young woman (24yrs, 173.5cm, 89kg, BMI: 29.6kg·m-2). Vascular and skeletal muscle function were assessed as part of a separate study with the first and second visits separated by 2 weeks. On the evening following the second visit, the participant developed a fever and a rapid antigen test confirmed a positive COVID-19 diagnosis. Compared to the first visit, the participant presented with a markedly elevated HR (~ 30 bpm) and lower mean blood pressure (~8 mmHg) at the second visit. Vascular function measured by brachial artery flow-mediated dilation, reactive hyperemia, and passive leg movement were all noticeably attenuated (25-65%) as was leg blood flow during knee extension exercise. Muscle strength was diminished as was ADP stimulated respiration (30%), assessed in vitro, while there was a 25% increase in the apparent Km. Lastly, an elevation in IL-10 was observed prior to symptom onset. Notably, 2.5 months after diagnosis symptoms of fatigue and cough were still present. Together, these findings provide unique insight into the physiological responses immediately prior to COVID-19 symptom onset; they suggest that SARS-CoV-2 negatively impacts vascular and skeletal muscle function prior to the onset of common symptoms and may set the stage for the widespread sequelae observed following COVID-19 diagnosis.

Background Hemodynamic perturbations in heart failure with preserved ejection fraction (HFpEF) may alter the distribution of blood in the lungs, impair gas transfer from the alveoli into the pulmonary capillaries, and reduce lung diffusing capacity. We hypothesized that impairments in lung diffusing capacity for carbon monoxide (DL CO ) in HFpEF would be associated with high mean pulmonary capillary wedge pressures during exercise. Methods and Results Rebreathe DL CO and invasive hemodynamics were measured simultaneously during exercise in patients with exertional dyspnea. Pulmonary pressure waveforms and breath‐by‐breath pulmonary gas exchange were recorded at rest, 20 W, and symptom‐limited maximal exercise. Patients with HFpEF (n=20; 15 women, aged 65±11 years, body mass index 36±8 kg/m 2 ) achieved a lower symptom‐limited maximal workload (52±27 W versus 106±42 W) compared with controls with noncardiac dyspnea (n=10; 7 women, aged 55±10 years, body mass index 30±5 kg/m 2 ). DL CO was lower in patients with HFpEF compared with controls at rest (DL CO 10.4±2.9 mL/min per mm Hg versus 16.4±6.9 mL/min per mm Hg, P <0.01) and symptom‐limited maximal exercise (DL CO 14.6±4.7 mL/min per mm Hg versus 23.8±10.8 mL/min per mm Hg, P <0.01) because of a lower alveolar‐capillary membrane conductance in HFpEF (rest 16.8±6.6 mL/min per mm Hg versus 28.4±11.8 mL/min per mm Hg, P <0.01; symptom‐limited maximal exercise 25.0±6.7 mL/min per mm Hg versus 45.5±22.2 mL/min per mm Hg, P <0.01). DL CO was lower in HFpEF for a given mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, pulmonary arterial compliance, and transpulmonary gradient. Conclusions Lung diffusing capacity is lower at rest and during exercise in HFpEF due to impaired gas conductance across the alveolar‐capillary membrane. DL CO is impaired for a given pulmonary capillary wedge pressure and pulmonary arterial compliance. These data provide new insight into the complex relationships between hemodynamic perturbations and gas exchange abnormalities in HFpEF.

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