Evidence map›Paper›PMID 34261487›Full record

ReviewFluids and barriers of the CNS2021

SARS-CoV-2: is there neuroinvasion?

Conor McQuaid, Molly Brady, Rashid Deane

Open access · goldAbstract readReview
In one paragraph

Review in Fluids and barriers of the CNS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Neurological, psychological, psychosocial complications of long-COVID and their management.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Infectious Diseases.Advances in neurobiology · 2024
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Conor McQuaidDepartment of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Molly BradyDepartment of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Rashid DeaneDepartment of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA. Rashid_Deane@urmc.Rochester.edu.ORCID http://orcid.org/0000-0002-0202-3551
University of Rochester · USUniversity of Rochester Medical Center · US

Funding

CSF/ISF highways for tau brain clearanceR21AG050212 · NIA · UNIVERSITY OF ROCHESTER · PI DEANE, RASHID · 2015 to 2016
$422k
DIFFERENTIAL SIGNALING OF M2 AND M4 MUSCARINIC RECEPTORSF32AG005774 · NIA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI WOTTA, DIANE R · 1996 to 1998
–
NIA NIH HHS AG050212NIA NIH HHS AG05774NIA NIH HHS F32 AG005774NIA NIH HHS R21 AG050212
6 · The paper itself

Abstract

backgroundSARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. MAIN BODY: We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways.

conclusionsWhile SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.

Indexed as

COVID-19HumansNervous System DiseasesPrognosisRisk FactorsACE2AgingBlood–brain barrier (BBB)Cerebrospinal fluid (CSF)Choroid plexusCOVID-19DiabetesHypertensionMMP9Obesity

Identifiers

PMID34261487
PMCPMC8278192
OpenAlexW3182736121

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.