Evidence map›Paper›PMID 34400495›Full record

ReviewProceedings of the National Academy of Sciences of the United States of America2021

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.

Bindu D Paul, Marian D Lemle, Anthony L Komaroff, Solomon H Snyder

Open access · greenAbstract readReview
In one paragraph

Review in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 1 pooled it
22.6field-weighted citation impact, top 1% 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

155 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.

  1. Pooled it
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  10. Fibromyalgia: A Multifactorial Pain Disorder.International journal of molecular sciences · 2026
    Review
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  18. Systematic Review of Randomized Clinical Trials for the Treatment of Long COVID Syndrome.Journal of community hospital internal medicine perspectives · 2026
    Article
  19. Article
  20. Article

95 more citing papers are in PubMed but not listed here.

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

4 authors at 3 institutions in 1 country.

Bindu D PaulDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205; bpaul8@jhmi.edu ssnyder@jhmi.edu.ORCID 0000-0002-1862-6103
Marian D LemleSolve ME/CFS Initiative, Glendale, CA 91206.ORCID 0000-0002-2284-2976
Anthony L KomaroffDepartment of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02120.ORCID 0000-0001-7672-2518
Solomon H SnyderDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205; bpaul8@jhmi.edu ssnyder@jhmi.edu.ORCID 0000-0002-6818-7022
Johns Hopkins University · USBrigham and Women's Hospital · USSolve ME/CFS Initiative · US

Funding

Project 3 : Clinical correlates and diagnostics in ME/CFSU54AI138370 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIPKIN, W. IAN · 2017 to 2022
$10.7M
Thorase Regulation of the Actions of CocaineP50DA044123 · NIDA · JOHNS HOPKINS UNIVERSITY · PI BARABAN, JAY M · 2018 to 2022
$9.0M
Neuroprotective actions of cystathionine g-lyase through gasotransmitter hydrogen sulfide signalingR01AG071512 · NIA · JOHNS HOPKINS UNIVERSITY · PI Bindu Paul · 2022 to 2026
$3.4M
Role of sulfhydration on the functions of the microtubule associated protein, TauR21AG073684 · NIA · JOHNS HOPKINS UNIVERSITY · PI PAUL, BINDU · 2021 to 2022
$450k
American Heart Association-American Stroke AssociationNIAID NIH HHS U54 AI138370NIA NIH HHS R01 AG071512NIA NIH HHS R21 AG073684NIDA NIH HHS P50 DA044123NIH HHS 5U54 AI138370NIH HHS DA044123
6 · The paper itself

Abstract

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called "long COVID-19," reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.

Indexed as

AnimalsCOVID-19EncephalomyelitisFatigue Syndrome, ChronicHumansOxidation-ReductionPost-Acute COVID-19 Syndromechronic fatigue syndromeCOVID-19mitochondriamyalgic encephalomyelitisredox

Identifiers

PMID34400495
PMCPMC8403932
OpenAlexW3195442125

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.