SWAlexander
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Abstract
With reports of diverse neurological deficits in the acute phase of COVID-19, there is a surge in neurological findings in Long-COVID—a protracted phase of SARS-CoV-2 infection. Very little is known regarding the pathogenic mechanisms of Neuro-COVID in the above two settings in the current pandemic. Herein, we hint toward the possible molecular mechanism that can contribute to the signs and symptoms of patients with neurological deficits and possible treatment and prevention modalities in the acute and chronic phases of COVID-19.
A. Introduction
Back during the early days of the pandemic, patients admitted to hospitals with COVID-19 exhibited a syndromic picture of neurological deficits caused by SARS-CoV-2. Later, a large group of patients with acute COVID-19 started emerging who continued to experience the effects of neurological damage caused by SARS-CoV-2 to the brain and spinal cord for periods ranging from months to over a year after the acute phase.1,2 Astonishingly, newer symptoms have been reported to appear, which with or without the symptoms suffered in the acute phase of COVID-19 have become the basis of the diagnosis of Long-COVID.2 Very little is known about the molecular mechanism(s) that could explain the neurological signs and symptoms of Long-COVID. For the acute phase of COVID-19, the contributing mechanisms have been coined, which include a combination of direct neuronal injury coupled with the damaging effects of the neuroinflammatory cytokines.1 The exploration into the pathological basis of the neurological signs and symptoms of Long-COVID remains a pivotal area of current research, as delays in knowing and targeting them could result in permanent disabilities in patients suffering from Long-COVID.1 Because the brain and spinal cord are rarely biopsied, and such an attempt can itself damage the neurological tissues, delays are expected to unravel the exact molecular and biochemical basis of the ongoing cellular injury causing the neurological signs and symptoms exhibited in Long-COVID. It is important to remark here that, though microscopic findings of the autopsied brains in Long-COVID are expected to clue toward the end lesions that caused fatality, like zones of gliosis and microinfarcts, they can contribute very little toward the mechanisms that had led to these changes. Likewise, imaging of the central nervous system (CNS) is important but could reveal only gross morphological changes and not mechanisms at the molecular level that contribute to worsening neurological features seen in Long-COVID. The factors contributing to the chronic phase neurological features in Long-COVID appear to be most likely cascades that had their origins in the acute phase and had continued into chronicity due to inadequate removal of SARS-CoV-2 and/or its proteins that continue neuronal injury in Long-COVID (Figure Figure11A,B). Ongoing inflammation and slowly evolving neurodegenerative changes due to SARS-CoV-2-mediated (Figure Figure11B3) direct neuronal and glial damage appear to be the underlying cause1 as it has been seen that neurological signs and symptoms (Figure Figure11A1) in Long-COVID continue to worsen with time (Figure Figure11A2) with findings of hypometabolism in neurons.3 No treatment is available at present for neurological damage reported in Long-COVID. A delay in recognition of this neurological damage is considered by many to be because of the myth it was a psychosomatic disorder without any organic basis for the syndromic presentation.
continue reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578368/
With reports of diverse neurological deficits in the acute phase of COVID-19, there is a surge in neurological findings in Long-COVID—a protracted phase of SARS-CoV-2 infection. Very little is known regarding the pathogenic mechanisms of Neuro-COVID in the above two settings in the current pandemic. Herein, we hint toward the possible molecular mechanism that can contribute to the signs and symptoms of patients with neurological deficits and possible treatment and prevention modalities in the acute and chronic phases of COVID-19.
A. Introduction
Back during the early days of the pandemic, patients admitted to hospitals with COVID-19 exhibited a syndromic picture of neurological deficits caused by SARS-CoV-2. Later, a large group of patients with acute COVID-19 started emerging who continued to experience the effects of neurological damage caused by SARS-CoV-2 to the brain and spinal cord for periods ranging from months to over a year after the acute phase.1,2 Astonishingly, newer symptoms have been reported to appear, which with or without the symptoms suffered in the acute phase of COVID-19 have become the basis of the diagnosis of Long-COVID.2 Very little is known about the molecular mechanism(s) that could explain the neurological signs and symptoms of Long-COVID. For the acute phase of COVID-19, the contributing mechanisms have been coined, which include a combination of direct neuronal injury coupled with the damaging effects of the neuroinflammatory cytokines.1 The exploration into the pathological basis of the neurological signs and symptoms of Long-COVID remains a pivotal area of current research, as delays in knowing and targeting them could result in permanent disabilities in patients suffering from Long-COVID.1 Because the brain and spinal cord are rarely biopsied, and such an attempt can itself damage the neurological tissues, delays are expected to unravel the exact molecular and biochemical basis of the ongoing cellular injury causing the neurological signs and symptoms exhibited in Long-COVID. It is important to remark here that, though microscopic findings of the autopsied brains in Long-COVID are expected to clue toward the end lesions that caused fatality, like zones of gliosis and microinfarcts, they can contribute very little toward the mechanisms that had led to these changes. Likewise, imaging of the central nervous system (CNS) is important but could reveal only gross morphological changes and not mechanisms at the molecular level that contribute to worsening neurological features seen in Long-COVID. The factors contributing to the chronic phase neurological features in Long-COVID appear to be most likely cascades that had their origins in the acute phase and had continued into chronicity due to inadequate removal of SARS-CoV-2 and/or its proteins that continue neuronal injury in Long-COVID (Figure Figure11A,B). Ongoing inflammation and slowly evolving neurodegenerative changes due to SARS-CoV-2-mediated (Figure Figure11B3) direct neuronal and glial damage appear to be the underlying cause1 as it has been seen that neurological signs and symptoms (Figure Figure11A1) in Long-COVID continue to worsen with time (Figure Figure11A2) with findings of hypometabolism in neurons.3 No treatment is available at present for neurological damage reported in Long-COVID. A delay in recognition of this neurological damage is considered by many to be because of the myth it was a psychosomatic disorder without any organic basis for the syndromic presentation.
continue reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578368/