Cell culture study: apoe4 makes brain cells make vulnerable to COVID

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Fiver
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Cell culture study: apoe4 makes brain cells make vulnerable to COVID

Post by Fiver »

I've been away for awhile. But I thought there might be interest in this study, if it hasn't already been discussed. Hope you are all well.

Cell Stem Cell
ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response

Shi and colleagues used hiPSC-derived neurons, astrocytes, and brain organoids to model SARS-CoV-2 neurotropism. They found that ApoE4/4 genotype led to an increased rate of SARS-CoV-2 infection in both neurons and astrocytes, and ApoE4 astrocytes exhibited a more severe response. Moreover, remdesivir could inhibit SARS-CoV-2 infection in neurons and astrocytes.

SUMMARY
ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe
COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of
direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes
that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and
ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes.
ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection.
Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes.
These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk fac-
tors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in
different patient populations.
NF52
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Re: Cell culture study: apoe4 makes brain cells make vulnerable to COVID

Post by NF52 »

Fiver wrote:I've been away for awhile. But I thought there might be interest in this study, if it hasn't already been discussed. Hope you are all well.

SUMMARY
ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe
COVID-19. [We] found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes.
ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection.
Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes.
These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk fac-
tors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects
in
different patient populations.
Welcome back, Fiver!

This is important info and consistent with reports at the Clinical Trials on AD (CTAD) this month. COVID-19 is no friend of ApoE4 and those who have it are more likely than non-carriers to have long-term effects. Happy that Thanksgiving comes this year with a serving of booster shots and first shots for little ones!
4/4 and still an optimist!
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