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Record W7117685100 · doi:10.1002/rmv.70101

Long Covid Syndrome and Role of Autonomic Nervous System

2025· article· en· W7117685100 on OpenAlexaboutno aff

Bibliographic record

VenueReviews in Medical Virology · 2025
Typearticle
Languageen
FieldMedicine
TopicLong-Term Effects of COVID-19
Canadian institutionsnot available
Fundersnot available
KeywordsAutonomic nervous systemmyalgiaDysgeusiaAnosmiaHeadachesNervous systemNeurological disorderDysautonomia

Abstract

fetched live from OpenAlex

Long Covid is a complex syndrome characterised by symptoms affecting several systems that persist for weeks and months after Covid-19 infection. A better understanding of this complex syndrome is important for the development of diagnostic and therapeutic strategies. In a meta-analysis of 257,348 COVID-19 patients, some of the most common long COVID symptoms at three to six months included fatigue (32%), dyspnoea (25%), and concentration difficulty (22%), reflecting the multisystemic nature of long COVID. In addition to these symptoms, there is a specific group of neurological symptoms and sequelae of long COVID. Some of the most common neurological symptoms persist for longer than a year after the initial diagnosis [1, 2]. Among the most common neurological symptoms these include fatigue (37%), brain fog (32%), memory problems (28%), attention disorders (22%), myalgia (28%), anosmia (12%), dysgeusia (10%) and headaches (15%) [3]. Overall, these symptoms can lead to significant dysfunction and disability. Recent evidence shows a functional deficit in the autonomic nervous system and responsible for symptomatic manifestations of long-term COVID-19. The dysfunction of the autonomic nervous system can partly explain the symptoms of long-COVID in different organs and systems of the body. Considering the different functions of the autonomic nervous system, and the distribution of peripheral autonomic nerves, it is logical to think that a dysfunctionality of the system can cause a variety of symptoms [4]. Among 106 post-COVID patients with high COMPASS-31 and modified Toronto Neuropathy (mTORONTO) symptom scores, 38 (36%) had neuropathic or autonomic complaints or both, associated with fatigue and headache [5]. An interesting study showed that among individuals with long COVID symptoms, orthostatic hypotension was the most frequently reported symptom [6]. Some evidence also suggests that the enteric nervous system may be a pathway of SARS-CoV-2 access into the body [7]. The underlying autonomic nervous system dysfunction may be an autoimmune/inflammatory explanation. An interesting study investigated the levels of several regulatory autoantibodies targeting G-protein coupled receptors (GPCRs) in 80 patients with long-term syndrome, with those of 38 healthy participants from anti-IgG seronegative controlSARS-CoV-2 and 40 post-symptomatic COVID112 individuals [8]. In general, patients with long-COVID syndrome had reduced levels of regulatory autoantibodies, and the strongest associations between levels of regulatory autoantibodies and disease outcomes concerned autoantibodies against β2 adrenoceptors, stabilin-1 and α2A adrenoceptors, and levels of regulatory antibodies were correlated with symptom severity in persons with long-COVID syndrome, particularly with vasomotor symptoms and chronic fatigue. In particular, increased severity of fatigue and vasomotor symptoms was positively associated with β2 adrenoceptor autoantibody levels in patients with long COVID syndrome [9]. On the basis of these considerations, it is logical to think that immunomodulation, and the administration of pharmacological agents acting on the sympathetic/parasympathetic system, could be functional and therapeutic in long COVID-19 syndrome, however, evidence in this direction is still scarce. In conclusion, the long-term COVID syndrome has yet to be fully understood and described, the pathophysiological and molecular mechanisms have not yet been completely described. Some recent evidence suggests that the dysfunction of the autonomic nervous system may be one of the concomitant causes, but in this direction there is still too little evidence for a complete demonstration. It would also be interesting to understand when the autonomic nervous system dysfunction occurs, so that it acts therapeutically effectively. Promising treatments already being studied clinically include drugs and biological agents targeting autoimmunity, drugs acting on adrenoreceptors, sympathetic ganglion block and transcranial electrical stimulation [10]. The author has nothing to report. The author has nothing to report. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. The author declare that the opinions expressed are of a personal nature and do not in any way commit the responsibility of the Administrations to which they belong.

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How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.388
Threshold uncertainty score0.547

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.318
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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