Lipids, amino acids, one-carbon metabolism, and energy pathway metabolites altered in Long COVID (PASC), with literature values and citations
How to read this page: Each metabolite is plotted as a box-and-whisker distribution: Healthy Control (blue) vs. Long COVID (teal). The TCA-cycle, amino-acid, and acylcarnitine entries below are built from the raw per-sample supplementary data of Guntur et al. 2022 (n=30 healthy controls, n=29 PASC) – true quartiles and ranges from LC-MS peak-area measurements, not literature-reported summary statistics. Lipid, homocysteine, and tryptophan entries instead use a published mean ± SD (or SE), with the box approximating the interquartile range assuming a roughly normal distribution – the underlying mean, SD, and n are always given in the reference row so you can check the source directly. A separate section below covers metabolites with real, cited significance but no extractable absolute values (mostly untargeted studies reporting only fold-change and p-value).
Where It Goes Wrong: The Mitochondrion in Long COVID
A cutaway of a single mitochondrion, annotated with eight sites of documented dysfunction in PACS/PACVS – from impaired protein import at the outer membrane through to disrupted fission/fusion dynamics and compensatory mitophagy. Directions shown are reduced, elevated, or mixed/compartment-dependent.
Protein import (TOM70–Hsp90): reduced (proposed) – SARS-CoV-2 ORF9b binds the mitochondrial translocase TOM70 and blocks its interaction with Hsp90 in vitro; the authors interpret this as a route to innate-immune (interferon) evasion. Downstream effects on mitochondrial protein import and oxidative phosphorylation are inferred, not measured in that study. Ayinde et al. 2022
mtDNA copy number: reduced – associated with impaired oxidative phosphorylation and metabolic inflexibility; lower copy number also predicts weaker immune response after vaccination. Ikezaki et al. 2023
Electron transport chain / ATP production: reduced – ME/CFS and PACS biopsy studies show impaired electron transport, reduced ATP production, and disrupted mitochondrial membrane potential.
TCA cycle intermediates: mixed by compartment – succinate, citrate, malate, pyruvate, and lactate reduced in PASC plasma (Guntur et al. 2022), but malate, citrate, and alpha-ketoglutarate elevated in COVID-19 monocytes (Ambikan et al. 2022) – tissue- and compartment-dependent.
β-oxidation / acylcarnitines: mixed by chain length – short-chain C2/C3 acylcarnitines reduced (impaired initial flux into β-oxidation), while medium- and long-chain acylcarnitines (C8–C18) and free fatty acids are elevated, consistent with incomplete oxidation and malonyl-CoA-mediated CPT-1 inhibition. Guntur et al. 2022
ROS & antioxidants: superoxide dismutase elevated (compensatory), while CoQ10 and glutathione are depleted; F2-isoprostanes and malondialdehyde (oxidative damage markers) are elevated.
Fission/fusion balance (MFN2, DRP1): both elevated – suggesting a disrupted balance between mitochondrial fusion and fission and reduced structural integrity of the electron transport chain.
Mitophagy (ATG4B): elevated – consistent with enhanced mitochondrial recycling as a compensatory response to accumulated damage.
Sources: Gracidas, Levy, Varon & Halma, "Lactate, Capnia, and Fat Oxidation as therapeutic axes for SARS-CoV-2 spike protein-induced sequelae," Hormone and Metabolic Research (in review); Guntur et al., Metabolites 2022; Ambikan et al., Cell Systems 2022; Ikezaki et al., iScience 2023; Ayinde et al., Biochimie 2022; Szögi et al., GeroScience 2024.
Filter by class:
All Metabolites (5)
Healthy Control
Long COVID Patients
Summary Statistics
Metabolite
Class
Group
Mean
Approx. IQR
Approx. Range
N
Directional Evidence: Metabolites Without an Extractable Absolute Value
Most Long COVID metabolomics studies are untargeted mass-spectrometry panels that report relative abundance, fold-change, and FDR-corrected p-values – not absolute concentrations in standard units. The findings below are real and cited, but shown as direction-of-change rather than box plots, since the source papers do not expose plottable numbers in their text (only in supplementary tables or figure images).
Kynurenine / Tryptophan Ratio Established
↑ Elevated – large, replicated effect
The kynurenine pathway diverts tryptophan away from serotonin synthesis. Its activation is one of the most consistently replicated metabolic findings in Long COVID, cross-validated by an independent meta-analysis.
Data: z-score of KYN/TRP ratio rises with severity: controls −0.104±0.889, mild Long COVID −0.302±0.876, severe Long COVID 0.760±1.043 (p<0.001, n=30/40/20). Meta-analysis of 14 studies (480 Long COVID vs 687 controls): SMD 0.755 [0.119, 1.392] for the ratio; kynurenine alone SMD 1.176; tryptophan alone SMD −0.520.
In a two-year follow-up cohort, glucose, kynurenine, pyruvic acid, and putrescine were all elevated in Long COVID compared to healthy controls, while glutamic acid and taurine were reduced – showing that some metabolic disturbances persist well beyond the acute and early post-acute phases.
Data: Long COVID n=48 vs. healthy controls n=37, two years post-infection. Glucose p=5×10⁻⁵, kynurenine p=3×10⁻⁴, pyruvic acid p=0.01, putrescine p=0.01; glutamic acid p=2.9×10⁻⁴, taurine p=1.3×10⁻³.
↔ Lower means observed, not statistically significant
Reported for completeness: both B12 and folate trended lower in long-term post-COVID recovery, but neither reached statistical significance in the one study identified – unlike homocysteine (see chart above), which was significantly elevated in the same cohort.
Sarcosine is reduced in Long COVID in two independent cohorts, and in one of them sarcosine (with serine) is inversely correlated with depression, anxiety, and cognitive dysfunction scores – making it one of the few metabolites with a direct symptom-severity link rather than just a group-mean difference. Spermidine is separately reported as reduced in a plasma fatty-acid/amino-acid survey of Long COVID patients.
Data: Serum sarcosine 0.877±0.313 μM in Long COVID (n=124) vs. 1.22±0.532 μM in ex-COVID controls (n=24), P=0.0002; serum phenylalanine did not differ in this cohort (68.3 vs. 72.6 μM, P=0.22) (Mikuteit et al.). Sarcosine and serine reductions with symptom-score correlations: metabolomic/immune profiling in Long COVID with chronic fatigue syndrome (Saito et al.). A phenylalanine reduction is not supported by either cohort. Synthesized in a 2025 mechanistic review proposing sarcosine (0.5–2 g/day) and serine repletion as candidate interventions.
Severity gradient matters: several of these metabolites (tryptophan, KYN/TRP ratio, HDL-cholesterol) shift non-monotonically or more strongly with Long COVID severity – a single "Long COVID" number can mask a mild-vs-severe split reported in the source study (noted in each reference row).
Approximated distributions: box plots above are derived from published mean ± SD (or SE), not literal reported quartiles – treat the box edges as an approximation of typical spread, not an exact IQR.
Untargeted vs targeted assays: the "Directional Evidence" metabolites come from untargeted metabolomics (relative abundance) rather than targeted, calibrated assays (absolute concentration) – useful for direction and mechanism, not for individual patient interpretation.
Research-only: most of these assays are not part of routine clinical care; homocysteine, B12, folate, and the lipid panel are the exceptions and are available through standard clinical labs.
Cite this page
Reusing these data? Please cite the tracker so others can find the source.
Open Source Medicine Foundation. (2026). Metabolite Alterations in Long COVID. Research Tracker. https://research.opensourcemed.info/long-covid-metabolites.html (accessed )
Weekly post-viral research digest
New peer-reviewed studies and trial activity across Long COVID, ME/CFS, PACVS, Lyme and Gulf War Illness, every week. Free, no spam.