Editor – We appreciate the letter from Dr. Mattioli1 regarding our article. Our study found that dysautonomia was common in long COVID and that its presence was associated with higher long COVID symptomatology on age- and gender-adjusted models. Dr. Mattioli has raised two important issues: First, the underrepresentation of women in our cohort and the need to further evaluate sex-related differences; and second, the importance of identifying dysautonomia as a potential future cardiovascular risk factor rather than solely a contributor to symptoms.
It is well established that in the United States the prevalence of long COVID is higher in women;2 however, women only represented 32% of our cohort. The most plausible explanation is that our cohort was assembled at a Veterans Affairs Healthcare System (VAHS), where women are generally underrepresented. Our proportion of women has been consistently higher than that reported by Bui et al.3 who examined a larger VAHS sample in which the prevalence of a long COVID diagnostic code (U09.9) was only 12%, but lower than observed in other cohorts.4 On further analysis, we found that men had significantly lower heart rate variability (SDNN: 49.6 ± 27.2 vs. 66.0 ± 36.8 ms in women; P = 0.02) but did not identify other significant sex differences in the prevalence of dysautonomia (Table 1). This finding may be explained by the small number of women in the sample, and we agree with Dr. Mattioli that the underrepresentation of women is a limitation that must be acknowledged in any study conducted within the VAHS.
Prevalence of dysautonomia by gender
Regarding cardiovascular risk, we agree with Dr. Mattioli that dysautonomia carries implications well beyond symptom burden. The COMPASS-31 is a valuable tool for capturing both cardiovascular and non-cardiovascular dimensions of autonomic dysfunction and their impact on overall symptomatology. Abnormal heart rate variability is an established predictor of sudden cardiac death in patients with and without known heart disease.5 Orthostatic hypotension and POTS are associated with decreased cerebral blood flow,6 preload failure,7 and endothelial dysfunction driven by hyperadrenergic responses.8 Whether these abnormalities translate into increased long-term cardiovascular morbidity in long COVID patients remains an important and unanswered question that future longitudinal studies should address.
- Received June 4, 2026.
- Accepted June 24, 2026.
References
- 1.↵Tamariz L, Rozenfeld I, Iglesias R, Dysautonomia in Long COVID is Prevalent and Could Explain the Frequency of Symptoms. Clin Med Res. 2026;24(1):28–34. doi:10.3121/cmr.2025.2054.
- 2.↵Shi J, Lu R, Tian Y, Prevalence of and factors associated with long COVID among US adults: a nationwide survey. BMC Public Health. 2025;25(1):1758. doi:10.1186/s12889-025-22987-8.
- 3.↵Bui DP, Bast E, Trinh H, Use of Long COVID Clinics in the Veterans Health Administration: Implications for the path forward. Health Aff Sch. 2025;3(5):qxaf080. doi:10.1093/haschl/qxaf080.
- 4.↵Eldokla AM, Mohamed-Hussein AA, Fouad AM, . Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study. Ann Clin Transl Neurol. 2022;9(6):778–785. doi:10.1002/acn3.51557.
- 5.↵Goldberger JJ, Arora R, Buckley U, Shivkumar K. Autonomic Nervous System Dysfunction: JACC Focus Seminar. J Am Coll Cardiol. 2019;73(10):1189–1206. doi:10.1016/j.jacc.2018.12.064.
- 6.↵van Campen CLMC, Visser FC. The Relation Between Cardiac Output and Cerebral Blood Flow in ME/CFS Patients with a POTS Response During a Tilt Test. J Clin Med. 2025;14(11):3648. doi:10.3390/jcm14113648.
- 7.↵Joseph P, Arevalo C, Oliveira RKF, Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chest. 2021;160(2):642–651. doi:10.1016/j.chest.2021.01.082.
- 8.↵Tamariz L, Shehadeh LA, Bast E, Klimas N, Palacio A. The role of the endothelium in long COVID. Vascul Pharmacol. 2026;163:107654. doi:10.1016/j.vph.2026.107654.
