Assessing autonomic nervous system imbalance in long COVID-19 patients through heart rate variability during tilt testing
Long COVID-19 is recognized as a condition associated with autonomic nervous system (ANS) dysfunction. However, quantitative evidence of its impact on heart rate variability (HRV) and blood pressure (BP) regulation during postural changes remains limited. This study assessed autonomic imbalance in post-COVID-19 patients by evaluating HRV and BP responses during tilt table testing, comparing long COVID-19 patients with healthy controls. A total of 61 participants were enrolled, 39 long COVID-19 patients (Study Group, SG) and 22 healthy controls (Control Group, CG). HRV was analyzed using time- and frequency-domain parameters. BP monitoring evaluated systolic, and diastolic blood pressure (SBP, and DBP respectively), and Pulse pressure (PP = SBP—DBP) was calculated for each phase. SG participants exhibited marked autonomic dysfunction during tilt. In the upright phase, they showed a significant increase in mean RR intervals ( p = 0.0136), reduced normalized low-frequency (LF † ) with p = 0.0316, increased normalized high-frequency (HF † ) with p = 0.0315, and a decreased low-frequency/high-frequency (LF/HF) ratio ( p = 0.0316), indicating a blunted sympathetic response and impaired autonomic adaptation to orthostatic stress. BP responses were also impaired: SG demonstrated attenuated changes in PP (ΔPP) when transitioning from the upright position to the recovery phase ( p < 0.037). Within-group analysis confirmed persistent RR interval instability ( p < 0.0001), incomplete normalization of LF and HF components (both p < 0.0001), and delayed recovery of PP after return to supine position. BP responses were also diminished: SG showed smaller ΔPP when moving from standing upright to the recovery phase ( p < 0.037). Baroreflex sensitivity values did not differ between groups. Long COVID-19 patients display significant autonomic dysregulation, characterized by reduced HRV, abnormal BP responses. These findings highlight the value of tilt testing in uncovering hidden dysautonomia and support the need for targeted interventions, including pharmacologic modulation and long-term HRV/BP monitoring, to improve cardiovascular stability in long COVID-19.
Authors
- Sílvia Helena Bastos de Paula (ORCID: https://orcid.org/0000-0002-4405-9405)
- Samuel Minucci Camargo
- Daniel Gustavo Goroso (ORCID: https://orcid.org/0000-0001-5454-9873)
- Jośe L. Puglisi (ORCID: https://orcid.org/0000-0003-0241-8446)
- Beatriz de Oliveira Machado (ORCID: https://orcid.org/0000-0003-0213-3723)
- Ana Leticia Gomes dos Santos
- Kelly Correa Baioco Da Silva
- Stella Tassinari Maximo
- Christian Gonçalves Sassaki (ORCID: https://orcid.org/0009-0004-7484-0640)
Institutions
- National University of Tucumán (AR)
- Faculdade São Leopoldo Mandic (BR)
- Instituto de Saúde (BR)
- Secretaria da Saúde (BR)
- California Northstate University (US)
- Universidade de Mogi das Cruzes (BR)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-06-24
- DOI
- https://doi.org/10.1038/s41598-026-38800-4
- Primary Topic
- Heart Rate Variability and Autonomic Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico