Acute Effects of Slow-Paced Breathing on Measures of HRV in Hospitalized Patients With Bilateral COVID-19 Pneumonia: A Secondary Analysis of a Randomized Clinical Trial Author: Elisabeth Maria Balint1, Beate Grüner, Harald Gündel, Sophia Haase, Mandakini Kaw-Geppert, Julian Thayer, Katja Weimer, Marc N Jarczok Affiliation: <sup>1</sup> From the Clinic for Psychosomatic Medicine and Psychotherapy, University Hospital Ulm (Balint, Gündel, Haase, Kaw-Geppert, Weimer, Jarczok), Ulm, Germany; Center for Mental Health, Privatklinik Meiringen (Balint), Meiringen, Switzerland; Clinic for Internal Medicine III, Division of Infectious Diseases (Grüner), University Hospital Ulm, Ulm, Germany; and Department of Psychological Science (Thayer), University of California, Irvine, Irvine, California. Conference/Journal: Psychosom Med Date published: 2025 Jan 1 Other: Volume ID: 87 , Issue ID: 1 , Pages: 74-83 , Special Notes: doi: 10.1097/PSY.0000000000001354. , Word Count: 297 Objective: Slow-paced breathing (SPB) with prolonged exhalation is assumed to stimulate vagal reflexes, which is represented by increased heart rate variability (HRV) values. However, most trials were conducted in healthy participants. We sought to evaluate the feasibility of SPB in hospitalized patients with confirmed bilateral COVID-19 pneumonia with major respiratory impairment and to investigate if SPB shows acute increasing effects on HRV measures in these severely ill patients with distinctly reduced vagal tone. Methods: This single-center randomized controlled clinical trial enrolled 23 patients in the intervention (4-second inhalation, 6-second exhalation for 20 minutes 3× daily) and 23 patients in the control group (IG/CG). The effects of SPB on HRV were calculated using post-hoc likelihood ratio tests. Baseline HRV measures between the groups over time were compared using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age. Results: HRV values at baseline were significantly decreased in all patients. During SPB, HRV parameters increased significantly (ln(SDNN), ln(LF), ln(TP); all p < .001). Higher breathing rate at baseline correlated with lower LF during SPB (p < .045). IL-6 morning levels were associated with lower HRV measures (p < .001). Resting HRV measures as well as subjective health increased over hospitalization time with no differences between IG and CG (comparing random slope with random slope interaction models: all LR χ2(5) < 4.5; p > .48). Conclusion: SPB is feasible and safe in patients with bilateral COVID-19 pneumonia and appears to be an effective self-performed intervention to acutely increase HRV measures. This observation was independent of comorbidities and comedication. Further trials should corroborate these findings and extend it to other severely ill populations. Registration: German Clinical Trials Register under ID DRKS00023971 (https://drks.de/search/en/trial/DRKS00023971), with a Universal Trial Number (UTN) U1111-1263-8658. PMID: 39701572 DOI: 10.1097/PSY.0000000000001354