Evidence map›Paper›PMID 34678659›Full record

ArticleJournal of the neurological sciences2021

Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients.

Erica Normandin, Kathryn B Holroyd, Sarah I Collens, Bennett M Shaw, Katherine J Siddle, Gordon Adams, Melissa Rudy, Isaac H Solomon, Melis N Anahtar, Jacob E Lemieux and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the neurological sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 4% 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026
    Review
  4. Article
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  8. Review
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  12. COVID-19: a multi-organ perspective.Frontiers in cellular and infection microbiology · 2024
    Review
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  17. Review
  18. Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Article
  19. Neuroinflammation and COVID-19.Current opinion in neurobiology · 2022
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 1 country.

Erica NormandinBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, United States of America.
Kathryn B HolroydDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Sarah I CollensDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Bennett M ShawBroad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
Katherine J SiddleBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, United States of America.
Gordon AdamsBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Melissa RudyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Isaac H SolomonDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, United States of America.
Melis N AnahtarDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United States of America.
Jacob E LemieuxBroad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
Bianca A TrombettaDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Pia KivisakkDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Steven E ArnoldDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Otto RapalinoDepartment of Radiology, Massachusetts General Hospital, Boston, MA, United States of America.
Anne L PiantadosiDepartment of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, United States of America.
Pritha SenDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
Eric S RosenbergDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
John BrandaDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United States of America.
Pardis C SabetiBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, United States of America; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America; Massachusetts Consortium on Pathogen Readiness, Boston, MA, United States of America; Howard Hughes Medical Institute, Chevy Chase, MD, United States of America.
Shibani S MukerjiDepartment of Neurology, Massachusetts General Hospital, Boston, MA, United States of America. Electronic address: smukerji@partners.org.
Massachusetts General Hospital · USBroad Institute · USBrigham and Women's Hospital · USConcord Consortium · USEmory University · USHarvard University · US

Funding

Immune Activation, Cerebral Metabolic Activity and Depression in Treated HIV-InfectionK23MH115812 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI MUKERJI, SHIBANI SHARON · 2018 to 2022
$926k
NIMH NIH HHS K23 MH115812
6 · The paper itself

Abstract

objectiveLittle is known about CSF profiles in patients with acute COVID-19 infection and neurological symptoms. Here, CSF was tested for SARS-CoV-2 RNA and inflammatory cytokines and chemokines and compared to controls and patients with known neurotropic pathogens.

methodsCSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein - 1β (MIP-1β)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n = 4) and 16 healthy controls (HC).

resultsMedian CSF cell count for COVID-19 patients was 1 white blood cell/μL; two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1β levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1β levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1β (r ≥ 0.6, p < 0.01) demonstrating the strongest associations.

conclusionsLack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.

Indexed as

COVID-19Blood-Brain BarrierCase-Control StudiesChemokinesCytokinesHumansInflammationRNA, ViralSARS-CoV-2ChemokinesCytokinesRNA, ViralCerebrospinal fluidCOVID-19InflammationNeurologySequencing

Identifiers

PMID34678659
PMCPMC8489278
OpenAlexW3204520488

What OpenQuestion holds

Textmetadata
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.