Weathering the Storm: Lung, Heart, and Brain Vascular Rehabilitation for COVID-19

Summary

Background: Respiratory and cardiovascular complications have emerged as dominant threats during and following coronavirus disease (COVID19) infection. Severe COVID19 infection is categorized as acute respiratory dysfunction leading to hospitalization, where as a mild infection is identified as symptoms of dyspnea, muscle pains, migraines, palpitations and/or fatigue persisting for several weeks. Recovery from COVID19 infection is poorly characterized, but symptoms appear to gradually decline over a four to eight-week period. Unfortunately, recovery from severe infection is similar to symptoms experienced with mild infection making it rather difficult to provide a physiological definition of recovery for mild infection sufferers. Considering that 81% of COVID19 infections are found to be mild, approximately 4.5 million Americans may be vulnerable to inadequate cardiovascular recovery that exacerbates reductions in physical capacity and quality of life. Combined respiratory muscle and exercise training enhance cardiorespiratory function, maximize return to activities of daily living, and reduces hospitalization times in heart failure, sepsis and severe acute respiratory syndrome. However, it is unclear if these interventions will also enhance cardiorespiratory and cerebrovascular COVID19 recovery. Therefore, utilizing cardiorespiratory and cerebrovascular rehabilitation techniques we propose these specific research aims and hypotheses to investigate the following:

1. Does individualized cardiac exercise rehabilitation enhance cardiorespiratory \& cerebrovascular recovery?

Hypotheses:
1. Individualized exercise therapy designed to increase fitness will enhance cardiorespiratory function at rest, as well as during and following exercise in individuals recovering from COVID19.
2. Cerebrovascular function at rest, as well as during and following exercise will be enhanced following individualized exercise therapy in individuals recovering from COVID19 infection.
3. The magnitude of post-training cardiorespiratory enhancements will be associated with cerebrovascular adaptations in individuals recovering from COVID19 infection.
2. Does combining inspiratory muscle and cardiac exercise rehabilitation provide additive cardiorespiratory and cerebrovascular COVID19 recovery benefits?

Hypotheses:

1. The addition of inspiratory muscle training to individualized exercise therapy will enhance cardiorespiratory adaptation in individuals recovering from COVID19 infection.
2. Improved cardiorespiratory function associated with inspiratory muscle training and exercise therapy will add further recovery advantage to cerebrovascular function in individuals recovering from COVID19 infection.

Study Design Scientific Plan: This project aims to collect pre- and post-intervention cardiorespiratory and cerebrovascular measures in individuals 1- 4 weeks after recovering from COVID19 infection (n=40; 20 ♀ \& 20♂). Each participant will be randomized to either Supervised Exercise Training (EXT; n=20) or combined inspiratory muscle and exercise testing (IMET; n=20) interventions. Randomization will match for age and sex, and will attempt balanced matching of any cardiovascular (hypertension, atherosclerosis), respiratory (chronic obstructive pulmonary disease, asthma), and metabolic (diabetes, metabolic syndrome) comorbidities between interventions. Prior to beginning EXT or IMET, participants will complete baseline fitness, respiratory muscle testing, cardiovascular, and cerebrovascular measures to DEXA body composition scan (dual energy X-ray absorptiometry, DEXA) determine the initial intensity and post-intervention effectiveness, respectively. Following baseline testing, participants will complete a 6-week EXT or IMET intervention. EXT: Supervised EXT will include a progressive individualized program that combines aerobic and resistance protocols. Volume progression will begin with 3-days of supervised training sessions/wk and will increase by 1 session/wk to a maximum of 5-days/wk. Each EXT session will include 30 minutes of aerobic training (15 minutes cycling; 15 minutes treadmill walking/running/elliptical) and 30 minutes of resistance training (specifics below). Considering individual fatigue will be a concern, therefore similar to exercise training standards in COPD, the duration of rest periods may be extended (\~1-3 min) as needed, however all exercise durations will be completed within a 1.5-hour time slot. IMET: All IMET sessions will be performed similar to EXT, with the exception of having 3-sessions of at home IMT training. On these days, all training will be spread out over a 2-hour session with periods of IMT training occurring at the beginning, middle and end of the session.

Conditions

• Covid19

Interventions

OTHER

Supervised Exercise Training Protocol

EXT: Supervised EXT will include a progressive individualized program that combines aerobic and resistance protocols. Volume progression will begin with 3-days of supervised training sessions/wk and will increase by 1 session/wk to a maximum of 5-days/wk. Each EXT session will include 30 minutes of aerobic training (15 minutes cycling; 15 minutes treadmill walking/running/elliptical) and 30 minutes of resistance training (specifics below). Considering individual fatigue will be a concern, therefore similar to exercise training standards in COPD, the duration of rest periods may be extended (\~1-3 min) as needed, however, all exercise durations will be completed within a 1.5-hour time slot. On days that EXT and IMET interventions overlap, the training and IMET will be spread out over a 2-hour session as opposed to the 1.5-hour time slot.

OTHER

Inspiratory Muscle and Exercise Training

Inspiratory Muscle Training (IMT): All IMT sessions will be performed similar to EXT, with the exception of having 2-3-sessions of at-home IMT training depending on where in the exercise progression the individual is (i.e., Week1 vs week 6). On the days that IMT and exercise training overlap, all training will be spread out over a 2-hour session with periods of IMT training occurring at the beginning, middle and end of the session. Each week will include a measure of Maximal Inspiratory Pressure (MIP) and a Test of Inspiratory Respiratory Endurance (TIRE). The intensity of the IMT will be 50% of the weekly MIP, thus progressive increases in IMT threshold intensity will remain at 50% of the weekly MIP. In contrast, the TIRE protocol will assess respiratory endurance based on the relative baseline intensity. Thus TIRE testing will begin at a MIP intensity of 50% (weeks 1-2), and then progressing to 65% (weeks 3-4), and 80% (weeks 5-6).

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• University of Illinois at Chicago

  lead OTHER

Principal Investigators

• Kurt Smith, PhD · University of Illinois at Chicago

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-15

Primary Completion

2021-08-30

Completion

2021-11-30

Countries

• United States

Study Locations