Autonomic conditioning therapy reduces fatigue and improves global impression of change in individuals with post-acute COVID-19 syndrome

Post-acute COVID-19 syndrome (PACS) is a collection of persistent and debilitating symptoms lasting weeks to months after acute COVID-19 infection, with fatigue most commonly reported. There is controversy surrounding the role of exercise programs for this condition, due to concerns over the potential to worsen fatigue. We developed a novel physical therapy program known as Autonomic Conditioning Therapy (ACT) for PACS, and report on the preliminary patient-reported outcome (PRO) data from individuals who completed ACT for PACS, compared with those who did not. Seventy-eight (55 [71%] female, median [range] age 43 [12 to 78]) met the inclusion criteria and consented to have their data included in the analyses. A total of 31 (40%) individuals completed ACT for PACS. There was within-group improvement in fatigue in individuals who completed ACT for PACS (mean difference [95% CI] -14 [-27 to -1], p = 0.03), as well as greater between-group impression of change measured on the Patient Global Impression of Change scale (ACT for PACS median [range] 5 [1 to 7], no ACT for PACS 4 [1 to 7], p < 0.01). ACT for PACS is a novel physical therapy program that can reduce fatigue in individuals with PACS.

Due to the highly debilitating nature and extreme lability of PACS symptoms, we developed a novel rehabilitation program known as Autonomic Conditioning Therapy (ACT) for PACS, which is an adaptation of well-established rehabilitative protocols for managing autonomic dysregulation. 16,17At present, there is controversy surrounding the role of exercise programs for this condition, due to concerns over the potential to worsen fatigue.This report compares preliminary longitudinal patient-reported outcome (PRO) data from individuals who completed ACT for PACS, with data from those who did not participate.
This was a retrospective cohort analysis.Participants provided consent for the publication of data and approval was provided by the Mount Sinai Program for Protection of Human Subjects (IRB 20-01985).
Inclusion criteria were individuals referred to the Mount Sinai PACS Clinic, with con rmed (by PCR or antibody test) or probable (diagnosed by a medical doctor in accordance with World Health Organization [WHO] recommendations) 18 prior diagnosis of COVID-19; diagnosed with PACS by a physician using NICE guidelines; 5 and, completed at least 21 days of ACT for PACS (if enrolled).Exclusion criteria were incomplete data (length of follow-up, fatigue).
Baseline demographic data was collected from individuals' electronic medical records.PRO data were collected with REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Mount Sinai Health System.A REDCap survey link was emailed to individuals.Baseline PRO data were collected from each participant upon enrollment into the PACS clinic as part of standard clinical care, starting in May 2020.This baseline set of PROs included a fatigue visual analogue scale (VAS), Medical Research Council [MRC] Breathlessness Scale, EuroQol health-related quality of life (EQ-5D-5L), Pain VAS, General Anxiety Disorder-7 (GAD-7) and WHO Disability Assessment Schedule (WHODAS).On March 15th 2021, the same PROs were repeated in all individuals, with the addition of the Patient Global Impression of Change (PGIC).
Following initial evaluation in the PACS clinic and cardiac clearance, it was recommended that individuals commence ACT for PACS.Individuals enrolled in ACT for PACS following the completion of 4 weeks of breath work coaching.Breath work coaching focused on ventilatory control and nasal breathing, and was conducted by Stasis (Virginia Beach, VA).ACT for PACS involved participating in 30-minute sessions twice per week physical therapist.This supervised program contained three distinct phases of rehabilitation beginning with supine active range of motion exercises, followed by progressive submaximal aerobic exercises. 17Submaximal exercise was monitored using the modi ed Borg Rate of Perceived Exertion (RPE), and individuals progressed through the phases according to RPE and symptom responses at the therapist's discretion (See supplementary material).Since inception, the ACT for PACS program has been implemented across 53 physical therapy centers in the greater New York area, which all completed standardized ACT for PACS training that was offered by the Mount Sinai Health System.The program was enacted via telehealth or in-person, according to each patient's preference and activity tolerance.
Statistical analyses were undertaken with Stata (StataCorp, Stata Statistical Software Release: V.14).Data are presented as frequencies and proportions, mean and standard deviation (SD) or median and range where appropriate.Paired Sample t-tests and Independent samples t-tests were used to examine between within-and between-group differences, presented as mean difference (95% con dence interval [CI]).Mann-Whitney U tests were used for between-group comparisons of PGIC and MRC.
Of 94 individuals, 84 (89%) met the inclusion criteria with complete data.Of these 84, 78 (93%) consented to have their data included in the analyses (Table 1).Three (4%) could not be reached and three declined to consent.Of the 78 who consented, 31 (40%) completed ACT for PACS (attending 5 of the trained centers) with the remaining 47 (60%) failing to enroll in the ACT for PACS program due to delays in administrative follow-up and/or referral to physical therapy, or by their own choice.For those in the ACT for PACS group, the median (range) time of participation was 64 (21 to 137) days.There were no within-or between-group differences observed in other outcomes.This is the rst intervention reported to successfully demonstrate a reduction in fatigue, the most common and debilitating symptom, in individuals with PACS.These improvements were re ected in the greater global impression of change in health reported by individuals when compared with a group who did not participate in the ACT program.Quantifying outcomes in a novel condition with a diverse set of debilitating symptoms can be di cult, and the use of PRO data was considered the best methodology for PACS.The most common symptoms reported in this cohort were fatigue, headache, di culty concentrating, dizziness/lightheadedness, memory loss, shortness of breath and palpitations.
Developing rehabilitation-based treatments for PACS is uniquely challenging, as most individuals are unable to tolerate traditional exercise and symptoms are often exacerbated with activity.Similar disease features are seen in disorders of the autonomic nervous system, including POTS.ACT for PACS was developed to address these rehabilitation constraints, using principles of graded submaximal aerobic exercise which are known to improve autonomic dysregulation and subsequent fatigue in POTS. 17One distinctive feature of ACT for PACS is that individuals progress according to symptom responses rather than elapsed time, resulting in slowly paced yet sustained recovery.Further prospective studies are needed to determine the optimal dose, mode and length of rehabilitation, level of supervision required, and to provide further insights into the characteristics of responders.

Table 2
Within-group and between group fatigue VAS data for individuals (n = 78) who completed ACT for PACS (n = 31) and those who did not (n = 47), including subgroups of individuals with either positive (n = 39) or negative/unknown COVID-19 (n = 39) con rmed by PCR and/or antibody tests.Data are presented as mean (SD) unless stated otherwise.Analyses performed using Paired and Independent Samples T tests.VAS = visual analogue scale, ACT = autonomic conditioning therapy, PACS = post-acute COVID-19 syndrome, Diff.= difference, CI = con dence interval.ACT for PACS n = 31, no ACT for PACS n = 47; b ACT for PACS n = 17, no ACT for PACS n = 22; c ACT for PACS n = 14, no ACT for PACS n = 25. a