Evidence map›Paper›PMID 41516190›Full record

ReviewInternational journal of molecular sciences2025

The Central Role of Macrophages in Long COVID Pathophysiology.

Philip Mcmillan, Anthony J Turner, Bruce D Uhal

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

3 authors.

Philip McmillanMcMillan Research Ltd., 71-75 Shelton Street, Covent Garden, London WC2H 9JQ, UK.
Anthony J TurnerFaculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.ORCID 0000-0001-8218-8198
Bruce D UhalDepartment of Physiology, Michigan State University, East Lansing, MI 48824, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically "trained" into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration.

Indexed as

COVID-19MacrophagesAnimalsEpigenesis, GeneticHumansImmunity, InnateMacrophage ActivationPost-Acute COVID-19 SyndromeSARS-CoV-2Spike Glycoprotein, CoronavirusSpike Glycoprotein, CoronavirusLong COVIDmacrophageMAIT cellsneuroinflammationPASC

Identifiers

PMID41516190
PMCPMC12785782

What Socratic 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 Socratic graph.