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Nature: Long-term Effects of SARS-CoV-2 Infection on Human Brain and Memory

Michael Coston

Editor, Senior Moderator
Nature: Long-term Effects of SARS-CoV-2 Infection on Human Brain and Memory


Credit Nature

#17,528

Just a couple of months into the COVID pandemic (Apr 2020) we saw the first major report (see JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease), on the neurological impact of COVID-19, one which found more than 1/3rd of a study group (n=214) hospitalized in Wuhan, China showed signs of neurological involvement.

Neurological manifestations ranged from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.).​

Since then we've seen dozens of reports on the neurological impact of COVID infection (see J. Neurology: COVID-19 As A Potential Risk Factor For Chronic Neurological Disorders), and concerns over its long-term effects on individuals and society (see Parkinsonism as a Third Wave of the COVID-19 Pandemic?).

Despite a 99% survival rate, among the `recovered' there are tens of millions of people whose health, and lives, have been severely impacted by the lingering effects of their COVID infection (see MMWR: Post–COVID Conditions Among Adult COVID-19 Survivors Aged 18–64 and ≥65 Years).​

Last month, in Study: SARS-CoV-2 Infection and Viral Fusogens Cause Neuronal and Glial Fusion that Compromises Neuronal Activity, the Queensland University's Brain Institute reported `. . . SARS-CoV-2 can cause brain cells to fuse, initiating malfunctions that lead to chronic neurological symptoms.'

To this growing list we can add the following report from the Journal Nature, which looks at the long-term impact of SARS-CoV-2 on the brain, routes the virus may take to invade the brain, and possible prevention strategies.​

Due to its length, I've only posted some excerpts. Follow the link to read it in its entirety. I'll have a postscript when you return.
Cell Death Discovery volume 9, Article number: 196 (2023) Cite this article

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with the high transmissibility and increased immune escape against vaccines. Because of the multiple basic amino acids in the S1-S2 junction of spike protein, the widespread distribution of angiotensin-converting enzyme 2 (ACE2) receptor in human body and the high transmissibility, SARS-CoV-2 can infect multiple organs and has led to over 0.7 billion infectious cases. Studies showed that SARS-CoV-2 infection can cause more than 10% patients with the Long-COVID syndrome, including pathological changes in brains.

This review mainly provides the molecular foundations for understanding the mechanism of SARS-CoV-2 invading human brain and the molecular basis of SARS-CoV-2 infection interfering with human brain and memory, which are associated with the immune dysfunction, syncytia-induced cell death, the persistence of SARS-CoV-2 infection, microclots and biopsychosocial aspects. We also discuss the strategies for reducing the Long-COVID syndrome. Further studies and analysis of shared researches will allow for further clarity regarding the long-term health consequences.

Facts

  • SARS-CoV-2 can cause Long-COVID syndrome in patients of different age groups.

  • SARS-CoV-2 can invade the neural system to interfere with human memory.

  • SARS-CoV-2 infection can induce cell death in multiple organs
Open questions

  • What are the mechanisms of SARS-CoV-2 infection causing Long-COVID syndrome?

  • What are the risk factors increasing the duration time and severity of Long-COVID syndrome?

  • How can we reduce the morbidity rate of Long-COVID syndrome and memory problems caused by SARS-CoV-2 infection?

  • What are the roles of biopsychosocial aspects affecting Long-COVID syndrome?
(SNIP)

Discussion

Because of the huge number of SARS-CoV-2 infectious cases, even 10% patients with Long-COVID symptoms can cause heavy burden to human society. The effects of SARS-CoV-2 infection on human brain and memory can affect children and adult’s development and their self-confidence. Current studies related to the effects of SARS-CoV-2 infection on human brain, especially the documented evidences of SARS-CoV-2 affecting human brain and memory have provided the convinced information to raise up the concern of the negative effects of Long-COVID on our daily life.

The possible routes of brain damages caused by SARS-CoV-2 infection (including direct viral infection in the brain, immune disfunction, and persistent viral infection) provided the information for better understanding how brain and memory can be affected. There are still largely unknown issues related to the brain damages directly and indirectly caused by SARS-CoV-2 infection.More studies are needed for further understanding Long-COVID pathogenesis.

Prevention strategies (including vaccination, antiviral and symptomatic treatment, wearing mask, suitable exercises, regular sleeping time, and balanced food supply) are important in reducing the risk factors of SARS-CoV-2 infection on human brain and memory, especially for children because they are young and their brains are in the early stage of development.
Long-COVID symptoms can affect their daily life more destructive with the long-term effects, such as suffering from the loss of memory abilities which can significantly affect their study efficiency and self-confidence before they grow up. Overall, further studies and knowledge about reducing the risks of SARS-CoV-2 infection and preventing SARS-CoV-2 infection can more effectively protect us from SARS-CoV-2 infection.

(Continue . . . )

Evidence that COVID is more than just a severe `flu' has continues to emerge, along with evidence that repeated infections may increase those risks. Post-COVID sequelae may include cardiovascular, renal, pulmonary, neurological, and endocrine disorders.

A few (of many) studies we've looked at over the past few months include:
While there is little doubt that Post-COVID syndrome is real, its full impact may not become apparent for many years (see here and here). Despite the desire to `normalize' COVID infections, and `get on with life', there are still plenty of good reasons to minimize exposure and avoid infection if you can.​

https://afludiary.blogspot.com/2023/07/nature-long-term-effects-of-sars-cov-2.html
 
"Fact - SARS-CoV-2 can invade the neural system to interfere with human memory"

I had not seen any evidence to support this, can anyone provide a link to a paper?
The article does state that viral RNA and protein had been found in the CNS, which I was aware of, but the histopathological research I learnt this from could not find any evidence of viral particles or viral reproduction. I was under the impression the neurological problems were due to glial cells being damaged by an over reactive immune system, but I may just not be up-to-date with the research.
If you are suffering from post infection neurological problems I don't suppose you care if it caused by virus in the CNS or immune over-exuberance but it may matter in terms of treatment during infection.
 
Thank you both.
I have not had time to read in detail but it seems that infection of cells inside the CNS is possible in vitro or by direct infection into the brain (in a mouse model). There does not seem to be evidence of virus penetrating the blood brain barrier and causing infection of susceptible CNS cells in us. The papers looking at neurological damage in long COVID patients concentrates on neuron damage/malformation with dysregulation of microglia due to cytokine imbalance which leads to their failure to correctly perform their housekeeping duties.

Edit:
On further reading this paper
https://rupress.org/jem/article/218...euroinvasion-of-SARS-CoV-2-in-human-and-mouse
appears to show some viral invasion in one patient (see figure 8) however the accompanying text includes
"Patient 3, who failed to regain consciousness after cessation of sedation, was diagnosed with severe global encephalopathy and was noted to have multiple diffuse microbleeds," which may offer an explanation of the mechanism of CNS breach. It is still not clear if long COVID neurological symptoms can be attributed directly to viral infection within the CNS.
 
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