Dysautonomia in Long COVID: Why Sex Differences Matter in Cardiovascular Risk Assessment

• Sex
• Gender
• Cardiovascular risk

Editor – I read with great interest the recent article by Tamariz et al.¹ on dysautonomia in long COVID, which highlights the high prevalence of autonomic dysfunction and its significant contribution to symptom burden. The authors should be commended for providing clinically relevant insights into the complex pathophysiology of long COVID and for emphasizing the importance of combining objective and subjective measures of autonomic dysfunction.

Their finding that dysautonomia, particularly when assessed through the Composite-Autonomic-Symptom-Score (COMPASS-31), is highly prevalent and correlates with symptom severity is of particular interest. This reinforces the concept that long COVID is a multisystem condition in which autonomic imbalance plays a central role.^1,2 Moreover, the observation that subjective measures may better capture patient experience than isolated objective tests is clinically meaningful and aligns with emerging evidence in other chronic conditions characterized by autonomic dysregulation.^1,2

However, I would like to expand the discussion by highlighting two aspects that deserve further attention: the cardiovascular implications of dysautonomia and the role of sex and gender differences in long COVID.

First, from a cardiovascular perspective, dysautonomia should not be viewed solely as a contributor to symptoms but also as a potential marker of future cardiovascular risk.^3,4 Alterations in heart rate variability, orthostatic responses, and autonomic tone are well-established predictors of adverse cardiovascular outcomes.⁴ In this context, the high prevalence of cardiovascular dysautonomia reported in this study (e.g., abnormal heart rate variability in 60% of patients) raises important questions regarding long-term cardiovascular monitoring and prevention strategies in patients with long COVID. As suggested by the authors, integrating tools such as cardiopulmonary exercise testing and orthostatic assessments may help identify patients at higher risk, but longitudinal studies are needed to determine whether these abnormalities translate into increased cardiovascular morbidity.^1,5

Second, and perhaps more importantly, the issue of sex differences warrants deeper consideration. In the present study, women accounted for only 32% of the cohort, which is somewhat unexpected given that previous literature suggests a higher prevalence of long COVID and dysautonomia-related conditions, such as postural orthostatic tachycardia syndrome (POTS), in women. This discrepancy raises the possibility of selection bias or underrepresentation and underscores the need for sex-specific analyses. Emerging evidence indicates that women are disproportionately affected by long COVID, both in terms of prevalence and symptom burden, particularly in domains related to fatigue, autonomic dysfunction, and immune dysregulation. In addition, sex-related differences in immune response, hormonal regulation, and endothelial function may contribute to the observed clinical heterogeneity. These aspects have been comprehensively discussed in recent literature, which emphasizes the importance of adopting a gender-sensitive approach in cardiovascular research and clinical practice.⁶

Importantly, the intersection between autonomic dysfunction and sex-specific cardiovascular risk may have broader implications. Women are known to present with different cardiovascular phenotypes, including microvascular dysfunction and syndromes characterized by autonomic imbalance.^7,8 In this context, long COVID may represent a unique model in which these mechanisms are amplified, offering an opportunity to better understand sex-specific pathophysiology.

Furthermore, the authors’ observation that gastrointestinal and orthostatic domains of the COMPASS-31 are strongly associated with symptom burden suggests that non-cardiovascular manifestations of dysautonomia are equally relevant. This supports a more holistic approach to patient evaluation, integrating cardiovascular, neurological, and systemic perspectives. Such an approach is particularly important in women, who often present with complex, multisystem symptoms that may be under-recognized or misattributed.

Finally, we agree with the authors that the discrepancy between subjective and objective measures of dysautonomia deserves further investigation. The dynamic nature of autonomic function and its susceptibility to environmental and physiological factors may limit the sensitivity of single-time-point assessments. In this regard, patient-reported outcomes, such as the COMPASS-31, provide valuable complementary information and may be particularly useful in clinical practice.

In conclusion, the study by Tamariz et al.¹ provides important evidence supporting the role of dysautonomia in long COVID. Future research should aim to clarify the long-term cardiovascular implications of these findings and to incorporate sex-specific analyses that reflect the known differences in disease presentation and outcomes. A multidisciplinary and gender-sensitive approach will be essential to improve both diagnosis and management of this complex condition.

• Received April 9, 2026.
• Accepted June 2, 2026.