Scientific reportsMar 3, 2026

Long COVID blood markers suggest no brain nerve damage or inflammation in the body or brain

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 4, 2026

Abstract

At a median of 69 weeks post-SARS-CoV-2 infection, no significant differences in markers of neuronal injury or inflammation were observed between long-COVID patients and recovered controls.

Long-COVID patients showed nominally elevated levels of inflammatory markers such as CRP, TNF-α, IL-6, and TREM2, but these differences did not hold after adjusting for multiple comparisons.
There were no observed differences in neurofilament light or glial fibrillary acidic protein levels, indicating a lack of ongoing neuronal injury or neuroinflammation.
The findings may suggest that persistent symptoms in long-COVID could stem from a chronic, low-level immune activation rather than direct central nervous system damage.
Potential mechanisms for lingering symptoms could involve pro-inflammatory signaling in the brain or changes in gene expression related to sickness behavior.
These results are preliminary and require further validation in larger, longitudinal studies.

Simplified

Long-COVID remains incompletely understood, particularly regarding the roles of peripheral systemic inflammation and neuroinflammation. The persistence and extent of these processes remain debated. We conducted a single-center, age- and sex-matched case-control study at Stavanger University Hospital, Norway, recruiting participants from the general population. Forty-eight long-COVID patients and 48 recovered controls were included at a median of 69 weeks post-SARS-CoV-2 infection. Exclusion criteria included autoimmune or chronic inflammatory diseases, cancer, and other conditions affecting fatigue. Plasma levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using ultrasensitive NULISA™ technology. CRP, TNF-α, and IL-6 were additionally assessed by a standard hospital laboratory method (CRP) and MSD S-Plex chemiluminescence immunoassay (TNF-α and IL-6 MSD). No significant differences in NfL or GFAP were observed between groups, suggesting no ongoing neuronal injury or neuroinflammation. Routine immunoassays showed no differences for inflammatory markers. In unadjusted analyses using ultrasensitive assays, long-COVID patients showed nominally elevated levels of CRP (p = 0.04), TNF-α (p = 0.01), IL-6 (p = 0.02), and TREM2 (p = 0.02). However, these differences did not survive correction for multiple comparisons (all false discovery rate-adjusted p > 0.05). The absence of neuroinflammation markers is consistent with the hypothesis that persistent long-COVID symptoms are unlikely due to ongoing neuronal injury or central nervous system inflammation. Alternatively, persisting long-COVID symptoms may reflect a chronic, extremely low-level immune activation, that contributes to fatigue, pain, and other sickness phenomena through mechanisms such as pro-inflammatory signaling in the brain, or epigenetic mechanisms underlying the sickness behavior response. These findings should be considered preliminary and warrant validation in larger, longitudinal cohorts.

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Competing interests

Declarations. Competing interests: RO, GDM, KT and ALB: None. HZ: HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merck Sharp & Dohme, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, ScandiBio Therapeutics AB, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, LabCorp, Lilly, Novo Nordisk, Oy Medix Biochemica AB, Roche, and WebMD, is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, and is a shareholder of MicThera (outside submitted work). TG: TG has received unrestricted research grants from AbbVie, Tillotts Pharma AB, has served as speaker for AbbVie, Ferring Pharmaceuticals, Takeda AS, and has been advisory board member for Takeda AS, Johnson & Johnson, Tillotts Pharma AB and Galapagos. Ethical approval: The study received ethical approval from the Regional Committee for Medical Research Ethics in Norway (REK vest 489162). All participants provided written informed consent to participate, and the study was conducted in accordance with the latest revision of the Helsinki Declaration. Consent for publication: All authors have read the final version of the manuscript and have consented for publication.

PubMed

Long COVID blood markers suggest no brain nerve damage or inflammation in the body or brain

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Competing interests

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