Potential autonomic nervous system dysfunction in COVID-19 patients detected by heart rate variability is a sign of SARS-CoV-2 neurotropic features

Abstract

Increasing evidence strongly support that the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the development of COVID-19-associated central nervous system (CNS) manifestations. The presence of SARS-CoV-2 viral protein in the brainstem, which includes cardiovascular control centers, has been documented previously. Given the changes in autonomic nervous system function evaluated by heart rate variability (HRV) metrics, which are observed even prior to clinical signs, the potential effect of SARS-CoV-2 on the autonomic nervous system (ANS) center is likely. The integral parts of the brain renin-angiotensin system, as ACE2 enzyme, are highly expressed in the brainstem, which may also be involved in baroreflex sensitivity, playing an important role in HRV. SARS-CoV-2 may bind to ACE2 in order to enter the host brainstem cell and change baroreflex sensitivity due to the altered ratio of the concentration of angiotensin II (Ag II) to angiotensin (1-7). In this article, we discussed the information on the possibility that the SARS-CoV-2 viral particle by disrupting the homeostasis of the brain renin-angiotensin system even without brainstem neuropathological changes, may affect the function of the ANS center in the brainstem. SARS-CoV-2 could influence ANS function before affecting the immune system. It is possible that the altered HRV parameters imply the potential neurotropic characteristics of SARS-CoV-2. Therefore, this potential feature should be taken into account in diagnostic and therapeutic approaches for COVID-19 patients.