Review Post-COVID dysautonomias: what we know and mainly what we don’t know, 2024, Goldstein, David S.

[SNT Gatchaman]

Post-COVID dysautonomias: what we know and mainly what we don’t know
Goldstein, David S.

Following on from the COVID-19 pandemic is another worldwide public health challenge that is referred to variously as long COVID, post-COVID syndrome or post-acute sequelae of SARS-CoV-2 infection (PASC). PASC comes in many forms and affects all body organs. This heterogeneous presentation suggests involvement of the autonomic nervous system (ANS), which has numerous roles in the maintenance of homeostasis and coordination of responses to various stressors.

Thus far, studies of ANS dysregulation in people with PASC have been largely observational and descriptive, based on symptom inventories or objective but indirect measures of cardiovascular function, and have paid little attention to the adrenomedullary, hormonal and enteric nervous components of the ANS. Such investigations do not consider the syndromic nature of autonomic dysfunction.

This Review provides an update on the literature relating to ANS abnormalities in people with post-COVID syndrome and presents a theoretical perspective on how the ANS might participate in common features of PASC.

Link | Paywall (Nature Reviews Neurology)

 

[SNT Gatchaman]

Key points

• The diverse nature of post-COVID syndrome suggests involvement of the autonomic nervous system (ANS), which plays numerous roles in homeostasis and coordinates responses to essentially all stressors.

• The ANS concept was promulgated before the discoveries of neuroendocrine systems, immune and inflammatory systems, and the central autonomic network; the extended autonomic system theory is a necessary update.

• Publications on post-COVID dysautonomias have not considered the syndromic nature of autonomic dysfunctions.

• Such studies have been largely observational and descriptive, based on symptom inventories or objective but indirect cardiovascular measures; the hormonal and enteric components of the ANS have generally been ignored.

• Understanding of multisystem disorders of regulation, such as post-COVID syndrome, requires a shift towards consideration of the feedback-regulated, plastic networks that, via the extended autonomic system, determine homeostasis and allostasis.

 

[SNT Gatchaman]

Review article that seeks to frame LC symptoms in terms of ANS dyshomeostasis. However does state —

Fatigue is the most difficult PASC symptom to explain. Fatigue might be a manifestation of an abnormal pattern of central neurotransmitters in brainstem and cortical pathways of the CAN and/or stress system.

Otherwise offering —

Most research in integrative physiology focuses on reflexes — regulatory processes that involve negative feedback loops. However, in humans, homeostasis also involves anticipatory feedforward processes that shift input–output curves and thereby bring levels of regulated variables to different plateau values (also known as set points), a process termed allostasis.

As all allostatic states waste energy reserves, fatigue can be anticipated to be a common feature of post-COVID syndrome. As an example, a variety of intervening physiological and biochemical variables could link important manifestations of PASC (POTS, a tendency to faint, brain fog and fatigue) to the [Extended Autonomic System].

Concludes with —

A key issue is that researchers investigating COVID-19 sequelae do not know what to look for because they have inadequate training in autonomic medicine. This is the ‘grand challenge’ of autonomic disorders. The author concurs with other investigators that having an Institute within the NIH focusing on complex chronic conditions, such as PASC, myalgic encephalomyelitis and/or CFS, and POTS, which could serve as prototype dysautonomias, would be beneficial.

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The author previously responded to Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome (2022, Brain) with Is postural tachycardia syndrome a psychogenic disorder? (2022, Brain) —

In summary, the study by Norcliffe-Kaufmann et al. provides evidence for the occurrence of a classically conditioned increase in heart rate in POTS patients, an enhanced adrenomedullary response to orthostasis and some abnormalities on psychiatric inventories.

These data are insufficient to infer that POTS is a psychiatric disorder, and the assertion that ‘These findings suggest that the postural tachycardia syndrome is a functional psychogenic disorder’ is an over-statement.