PMID- 34678659
OWN - NLM
STAT- MEDLINE
DCOM- 20211116
LR  - 20221217
IS  - 1878-5883 (Electronic)
IS  - 0022-510X (Print)
IS  - 0022-510X (Linking)
VI  - 430
DP  - 2021 Nov 15
TI  - Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in 
      the CSF of COVID-19 hospitalized patients.
PG  - 120023
LID - S0022-510X(21)02725-8 [pii]
LID - 10.1016/j.jns.2021.120023 [doi]
AB  - OBJECTIVE: Little 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. METHODS: CSF 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 - 1beta (MIP-1beta)) 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). RESULTS: Median CSF cell count for 
      COVID-19 patients was 1 white blood cell/muL; 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-1beta levels were higher than HC and suppressed 
      HIV (corrected-p < 0.05). MCP-1 and MIP-1beta 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-1beta (r >/= 0.6, p < 0.01) 
      demonstrating the strongest associations. CONCLUSIONS: Lack 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.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Normandin, Erica
AU  - Normandin E
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Systems 
      Biology, Harvard Medical School, Boston, MA, United States of America.
FAU - Holroyd, Kathryn B
AU  - Holroyd KB
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Collens, Sarah I
AU  - Collens SI
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Shaw, Bennett M
AU  - Shaw BM
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious 
      Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
FAU - Siddle, Katherine J
AU  - Siddle KJ
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Systems 
      Biology, Harvard Medical School, Boston, MA, United States of America.
FAU - Adams, Gordon
AU  - Adams G
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Rudy, Melissa
AU  - Rudy M
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Solomon, Isaac H
AU  - Solomon IH
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States 
      of America.
FAU - Anahtar, Melis N
AU  - Anahtar MN
AD  - Department of Pathology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Lemieux, Jacob E
AU  - Lemieux JE
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Infectious 
      Diseases, Massachusetts General Hospital, Boston, MA, United States of America.
FAU - Trombetta, Bianca A
AU  - Trombetta BA
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Kivisakk, Pia
AU  - Kivisakk P
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Arnold, Steven E
AU  - Arnold SE
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Rapalino, Otto
AU  - Rapalino O
AD  - Department of Radiology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Piantadosi, Anne L
AU  - Piantadosi AL
AD  - Department of Pathology and Laboratory Medicine, Emory School of Medicine, 
      Atlanta, GA, United States of America.
FAU - Sen, Pritha
AU  - Sen P
AD  - Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 
      United States of America.
FAU - Rosenberg, Eric S
AU  - Rosenberg ES
AD  - Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 
      United States of America.
FAU - Branda, John
AU  - Branda J
AD  - Department of Pathology, Massachusetts General Hospital, Boston, MA, United 
      States of America.
FAU - Sabeti, Pardis C
AU  - Sabeti PC
AD  - Broad 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.
FAU - Mukerji, Shibani S
AU  - Mukerji SS
AD  - Department of Neurology, Massachusetts General Hospital, Boston, MA, United 
      States of America. Electronic address: smukerji@partners.org.
LA  - eng
PT  - Journal Article
DEP - 20211004
PL  - Netherlands
TA  - J Neurol Sci
JT  - Journal of the neurological sciences
JID - 0375403
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Blood-Brain Barrier
MH  - *COVID-19/physiopathology
MH  - Case-Control Studies
MH  - Chemokines
MH  - Cytokines
MH  - Humans
MH  - Inflammation/*virology
MH  - RNA, Viral/*cerebrospinal fluid
MH  - SARS-CoV-2
PMC - PMC8489278
OTO - NOTNLM
OT  - COVID-19
OT  - Cerebrospinal fluid
OT  - Inflammation
OT  - Neurology
OT  - Sequencing
COIS- JEL has received consulting fees from Sherlock biosciences. PCS is a co-founder 
      of, shareholder in, and scientific advisor to Sherlock biosciences, Inc., as well 
      as a board member of and shareholder in Danaher corporation. MNA is a co-founder 
      and equity holder of Day zero diagnostics, outside of the submitted work. All 
      other others report no relevant declarations
EDAT- 2021/10/23 06:00
MHDA- 2021/11/17 06:00
PMCR- 2021/10/04
CRDT- 2021/10/22 20:46
PHST- 2021/05/19 00:00 [received]
PHST- 2021/09/06 00:00 [revised]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/10/23 06:00 [pubmed]
PHST- 2021/11/17 06:00 [medline]
PHST- 2021/10/22 20:46 [entrez]
PHST- 2021/10/04 00:00 [pmc-release]
AID - S0022-510X(21)02725-8 [pii]
AID - 120023 [pii]
AID - 10.1016/j.jns.2021.120023 [doi]
PST - ppublish
SO  - J Neurol Sci. 2021 Nov 15;430:120023. doi: 10.1016/j.jns.2021.120023. Epub 2021 
      Oct 4.