ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response
Wang C, Zhang M, Garcia G, Tian E, Cui Q, Chen X, Sun G, Wang J et al.. Cell stem cell, 2021-01-04
Topic: Brain proteins, microglia and lab models
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 factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.
Key findings
- ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19.
- These findings suggest that ApoE4 may play a causal role in COVID-19 severity.
Why it matters
In human stem cell models, ApoE4 was associated with a higher rate of SARS-CoV-2 infection in neurons and astrocytes, and remdesivir inhibited the infection in these cells. This is laboratory work about COVID-19 and ApoE4, not a study of treating or preventing Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell stem cell) |
| Journal's citation record | 3 / 4 | Cell stem cell: journal h-index 372 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 223 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 14.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 54 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Yanhong Shi: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33450186) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
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Read the original
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APA 7th
Wang, C., Zhang, M., Garcia, G., Tian, E., Cui, Q., Chen, X., et al. (2021). ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response. Cell stem cell. https://doi.org/10.1016/j.stem.2020.12.018
Vancouver
Wang C, Zhang M, Garcia G, Tian E, Cui Q, Chen X, et al. ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response. Cell stem cell. 2021. doi:10.1016/j.stem.2020.12.018. PMID: 33450186.
BibTeX
@article{wang2021-33450186,
author = {Wang, C. and Zhang, M. and Garcia, G. and Tian, E. and Cui, Q. and Chen, X. and Sun, G. and Wang, J. and others},
title = {{ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response}},
journal = {Cell stem cell},
year = {2021},
doi = {10.1016/j.stem.2020.12.018},
pmid = {33450186},
url = {https://doi.org/10.1016/j.stem.2020.12.018}
}
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