Insights into COVID-19 pathophysiology from a longitudinal multisystem report during acute infection, 2024, Brihmat et al.

Insights into COVID-19 pathophysiology from a longitudinal multisystem report during acute infection
Brihmat; Bayram; Bheemreddy; Saleh; Yue; Forrest

The Coronavirus disease 2019 (COVID-19), an illness caused by a SARS-CoV-2 viral infection, has been associated with neurological and neuropsychiatric disorders, revealing its impact beyond the respiratory system. Most related research involved individuals with post-acute or persistent symptoms of COVID-19, also referred to as long COVID or Post-Acute Sequelae of COVID-19 (PASC).

In this longitudinal unique report, we aimed to describe the acute supraspinal and corticospinal changes and functional alterations induced by a COVID-19 infection using neuroimaging, neurophysiological and clinical assessment of a participant during acute infection, as compared to three other visits where the participant had no COVID-19. The results favor a multisystem impairment, impacting cortical activity, functional connectivity, and corticospinal excitability, as well as motor and cardiovascular function.

The report suggests pathophysiological alteration and impairment already present at the acute stage, that if resolved tend to lead to a full clinical recovery. Such results could be also insightful into PASC symptomatology.

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This was a serendipitous case report of a healthy 37yo male taking part in a study of transcutaneous stimulation motor training who developed acute Covid at the third study time point.

Quick precis —

• we describe a within-subject longitudinal report of neuroimaging, neurophysiological and functional motor and cardiovascular outcome measures obtained with an able-bodied individual during four visits, one of which the later complained of fatigue, low energy / difficulty concentrating, and headache, and was a posteriori tested positive for COVID-19

• part of a pilot study investigating the supraspinal and corticospinal effects of spinal cord transcutaneous stimulation (scTS)-based motor training versus motor training alone in a Pre/Post intervention design

• V3), the participant reported mild fatigue, low energy, difficulty concentrating, and headache

• same evening, he tested positive for SARS-CoV-2, first known infection

• During the other visits, the participant did not report or show any residual sign of neurological, neuropsychiatric, or functional deficit

• V4, no persistent COVID-19 related symptoms

• At V3, during the acute infection, the activation appears exacerbated and more bilateral compared to that observed at V2 and V4, especially for RH grip

• Adding cardiovascular data as physiological regressors during the preprocessing of the fNIRS data did not change the overall pattern of activation within and between visits (results not shown), ruling out the potential confound of the fNIRS results by difference in cardiovascular function.

• At V3, during the acute COVID-19 infection, the participant showed an average SBP at 135 mmHg, a DPB at 82 mmHg, a HR at 82 bmp and an average blood oxygenation level at 97.3%. Despite slightly higher cardiovascular outcome values, only the SBP falls slightly outside the physiological range of the participant (2 values out of 3 higher than 134.97 mmHg).

• To our knowledge, not many studies, if any, performed a multisystem evaluation investigating supraspinal and corticospinal function during an acute COVID-19 infection.

• Here, we report the retrospective multisystem changes observed in a participant during an acute COVID-19 infection as compared to that of other visits where the participant did not show any sign of neurologic or functional dysfunction.

• When analyzing the data obtained from the visit that turned out to be performed while the participant was suffering from SARS-CoV-2 infection, relative increases in bilateral sensorimotor activation during handgrip tasks, overall reduced resting-state intra- and interhemispheric functional connectivity between cortical prefrontal, frontal, and parietal regions, increased corticospinal excitability, reduced intracortical inhibition, decreased maximal handgrip and pinch strength and increased autonomic cardiovascular functioning were observed.

• consistent with other reports at later post-acute stages

• complemented here by the additional report on changes in resting state functional connectivity and cortical activation during the performance of a motor tasks.

• we report increased and more bilateral sensorimotor frontoparietal activation during handgrip tasks at V3 despite similar grip force produced during task trials, compared with the other visits

• findings support the idea of a more desynchronized system with potential compensatory neural activations and processes to produce muscular output necessary to maintain “normal” task performance

• a lateralized and more focused activation pattern is often associated with a better synchronization of the descending volley and/or responsiveness of motoneurons to supraspinal input which results in better control of movement and force

• The lower functional connectivity observed at rest could reflect the lower efficiency of the networks during acute COVID-19 infection with less functional communication between regions appertaining at the same network to potentially limit excessive energy consumption at rest.

• lesser focused and more bilateral cortical activation during motor task performance and weaker functional connectivity between frontoparietal regions at rest may reflect less optimal state of the brain during the acute COVID-19 infection and the pathways activity dysregulation, due to the ongoing pathophysiological processes, which could potentially explain the dysexecutive and “brain fog” symptom experienced by COVID-19 individuals

• Contrary to some previous reports, we show evidence of corticospinal excitability increases as reflected with MEP amplitude increases and MT decreases in the participant tested during V3, as compared to the other visits.

• could be due to the GABAergic neurotransmission dysregulation that could lead to inefficient regulation of brain internal states

• or to reflects compensatory pathways to maintain normal functioning

• or to the excitotoxicity induced by the inflammation

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• For example, to produce a similar level of grip strength during the task (Fig. 1A), more voluntary drive from supraspinal centers could be needed to compensate for the lack of resources and pathways disorganization and this might explain the higher brain activity and corticospinal excitability observed.

• The case described in our report was at an early stage of infection, judging by the relative recent onset of the symptoms, and presented with a benign course of the disease, which resolved within a week.