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Peptides for Post-COVID Recovery

If you're months past a COVID-19 infection and still dealing with fatigue, brain fog, shortness of breath, or exercise intolerance, you're not imagining it. Post-acute sequelae of SARS-CoV-2 infection — what most people call long COVID — affects an estimated 10-20% of people after infection.

If you're months past a COVID-19 infection and still dealing with fatigue, brain fog, shortness of breath, or exercise intolerance, you're not imagining it. Post-acute sequelae of SARS-CoV-2 infection — what most people call long COVID — affects an estimated 10-20% of people after infection. And for many, standard treatments offer limited relief.

This has pushed researchers and clinicians toward peptide therapy as a potential piece of the recovery puzzle. Not because peptides are a magic fix — they aren't. But because the underlying biology of long COVID involves immune dysfunction, mitochondrial damage, chronic inflammation, and tissue injury. These are exactly the pathways that specific peptides target.

This guide covers the science of why long COVID persists, which peptides are being studied and used for recovery, what the evidence actually shows, and what to know before pursuing peptide therapy for post-COVID symptoms.

Table of Contents

What Makes Long COVID So Difficult to Treat

Long COVID isn't one disease. It's a collection of symptoms — fatigue, cognitive dysfunction, exercise intolerance, shortness of breath, joint pain, gut problems, and dozens more — that share overlapping but distinct biological drivers. A 2025 review in Comprehensive Physiology identified multiple interacting mechanisms, including viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances [1].

This complexity is precisely why no single drug has emerged as a cure. And it's why peptide therapy, which targets specific biological pathways rather than specific symptoms, has drawn attention from researchers and integrative practitioners.

The Four Pillars of Long COVID Biology

Understanding why certain peptides are being explored for long COVID recovery requires understanding the biology driving the condition. Research has identified four core mechanisms:

1. Immune Dysregulation

SARS-CoV-2 can form reservoirs in tissue, evading immune clearance while triggering chronic immune activation. Studies have found elevated plasma levels of inflammatory markers — TNF-alpha, IL-6, IL-1-beta, and CXCL-10 — in long COVID patients [1]. T cells show signs of exhaustion, with depletion of naive B and T cell populations and expansion of memory T cells, suggesting the immune system is stuck in a state of chronic stimulation [2].

2. Mitochondrial Dysfunction

Chronic fatigue and exercise intolerance — two hallmark symptoms of long COVID — are increasingly linked to mitochondrial damage. SARS-CoV-2 viral proteins (particularly ORF9b, ORF3a, and NSP13) directly interfere with mitochondrial function, disrupting energy production and the innate immune signaling that mitochondria coordinate [3]. A 2024 study in GeroScience described how this creates a self-sustaining loop: damaged mitochondria produce excessive reactive oxygen species, which triggers more inflammation, which causes more mitochondrial damage [4].

3. Chronic Inflammation

The inflammatory feedback loops in long COVID go beyond normal post-infection recovery. Overactivated monocytes produce excess cytokines, creating positive feedback cycles that persist long after the virus is cleared. This low-grade, sustained inflammation affects the brain (contributing to fog), the vasculature (contributing to clotting risk), and nearly every organ system [1].

4. Tissue and Vascular Damage

COVID-19 causes direct damage to endothelial cells (the cells lining blood vessels), lung tissue, cardiac tissue, and the gut lining. Microclotting, fibrosis, and impaired blood flow contribute to ongoing symptoms even when the active infection has resolved.

Peptides Under Investigation for Post-COVID Recovery

Immune Restoration: Thymosin Alpha-1

Thymosin Alpha-1 (Ta1) is a 28-amino-acid thymic peptide approved in over 35 countries for hepatitis B, hepatitis C, and immune enhancement. It works by supporting T cell maturation, improving interferon production, and helping resolve chronic inflammation — all directly relevant to the immune dysregulation seen in long COVID.

What the research shows:

A 2023 study published in International Immunopharmacology specifically tested Ta1 on blood cells from long COVID (PASC) patients. The findings were notable: Ta1 significantly reduced expression of IL-6 and the activation markers CD38 and HLA-DR in both CD4+ and CD8+ T cells from COVID patients [5]. The decrease in CD38 on CD8+ T cells was also significantly associated with clinical status, suggesting the effect was biologically meaningful rather than just a laboratory finding.

During acute COVID-19, Ta1 was used widely in China, where some studies reported decreased hospitalization rates and reduced mortality by restoring depleted T cell counts [6]. However, the evidence was mixed — a Frontiers in Immunology study found that Ta1 did not significantly improve CD4+ or CD8+ T cell recovery compared to standard care alone [7].

Current status: Ta1 has the strongest regulatory track record of any peptide being discussed for long COVID, with decades of clinical use across multiple countries. Its specific application to PASC is supported by mechanistic data and one targeted in vitro study, but randomized controlled trials in long COVID patients are still needed. For more on immune-supporting peptides, see our Best Peptides for Immune Support guide.

Mitochondrial Repair: SS-31 and MOTS-c

SS-31 (Elamipretide)

SS-31 is a synthetic tetrapeptide that targets the inner mitochondrial membrane by binding to cardiolipin, a phospholipid that plays a central role in electron transport chain function. This binding stabilizes the mitochondrial membrane, reduces reactive oxygen species (ROS) production, and improves ATP generation [8].

In September 2025, the FDA granted accelerated approval to elamipretide for Barth syndrome, a rare mitochondrial disorder — making it the first mitochondria-targeted peptide to receive FDA approval for any condition [9]. Clinical trial data showed significant improvements in exercise tolerance (measured by the 6-minute walk test) after 48 weeks of treatment.

For long COVID, the relevance is direct: if mitochondrial dysfunction drives fatigue, exercise intolerance, and cognitive symptoms, a peptide that specifically repairs mitochondrial function addresses the root cause rather than the symptoms.

MOTS-c

MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA that functions as an exercise mimetic. In animal studies, MOTS-c administration activated AMPK, improved insulin sensitivity, and increased running capacity — even in old mice [10]. A 2021 study in Nature Communications showed that late-life MOTS-c treatment increased physical capacity and improved metabolic markers [11].

For long COVID patients who can't exercise due to post-exertional malaise, a compound that provides some of the metabolic benefits of exercise without requiring physical exertion is conceptually appealing. However, MOTS-c has not yet advanced to human clinical trials for any condition, and challenges with bioavailability and stability have slowed development.

Tissue Healing and Inflammation: BPC-157 and TB-500

BPC-157

BPC-157 is a 15-amino-acid gastric peptide that modulates nitric oxide pathways, upregulates VEGF (vascular endothelial growth factor), and stimulates collagen production [12]. In the context of long COVID, practitioners use it for gut healing (COVID can damage the GI lining), anti-inflammatory effects, and vascular repair.

A 2024 systematic review examining 36 preclinical studies (1993-2024) confirmed BPC-157's healing-promoting effects across muscle, tendon, ligament, and bone injury models, with no adverse effects observed in animal studies [13]. However, only three published studies have tested BPC-157 in humans, and none specifically in long COVID patients.

TB-500

TB-500 supports vascular regeneration, reduces inflammation, and promotes cell migration to injury sites through its regulation of actin polymerization [14]. Its systemic effects make it relevant to the widespread endothelial damage and microclotting seen in long COVID.

When used together, BPC-157 and TB-500 target different aspects of tissue repair — BPC-157 works locally (angiogenesis, collagen, growth factors) while TB-500 works systemically (cell migration, cytoskeletal repair). See our Peptide Stacking Guide for more on how these two are combined.

Antimicrobial and Antiviral Support: LL-37

LL-37 is a naturally occurring human cathelicidin — an antimicrobial peptide produced by immune cells and epithelial cells in the skin and respiratory tract. It has direct antiviral activity: surface plasmon resonance (SPR) analysis has shown that LL-37 binds to the SARS-CoV-2 spike protein and blocks its interaction with the ACE2 receptor [15].

A 2025 study in Frontiers in Cellular and Infection Microbiology expanded on these findings, demonstrating that LL-37 also binds to SARS-CoV-2 accessory proteins ORF7a and ORF8, disrupting multiple viral-host interactions [16]. In a separate study, LL-37 increased rhinovirus-induced interferon-beta expression in human airway cells and reduced viral load by about 40% [17].

For long COVID specifically, LL-37 is relevant because of the viral persistence hypothesis — the theory that SARS-CoV-2 or its fragments persist in tissues, driving chronic immune activation. If viral reservoirs contribute to ongoing symptoms, a peptide with direct antiviral activity could theoretically help clear those reservoirs.

LL-37 is also linked to vitamin D metabolism. It is upregulated by vitamin D, which has led researchers to speculate that vitamin D supplementation may improve COVID outcomes partly through increased LL-37 production [15].

An early clinical trial of oral LL-37 (delivered via engineered Lactococcus lactis) showed preliminary safety and symptom improvement in COVID patients, with a follow-up randomized trial testing it against the Omicron BA.5.1.3 variant [18].

Anti-Inflammatory Support: KPV and VIP

KPV

KPV is a tripeptide derived from alpha-melanocyte-stimulating hormone (alpha-MSH) with potent anti-inflammatory properties. It is sometimes administered intranasally in long COVID protocols, targeting neuroinflammation and mast cell activation — both implicated in brain fog and post-COVID sensitivities.

VIP (Vasoactive Intestinal Peptide)

VIP is a 28-amino-acid peptide with both anti-inflammatory and vasodilatory properties. It has been studied in pulmonary conditions and is used by some practitioners for post-COVID respiratory symptoms and chronic inflammatory response syndrome (CIRS). VIP helps regulate immune responses in the lungs and gut, two organ systems commonly affected by long COVID.

Growth Hormone Axis: CJC-1295 and Ipamorelin

The growth hormone (GH) axis plays a role in tissue repair, immune function, body composition, and sleep quality — all of which can be disrupted in long COVID. CJC-1295 and Ipamorelin stimulate GH release through complementary pathways (GHRH receptor and ghrelin receptor, respectively) [19, 20].

For long COVID patients experiencing muscle wasting, poor recovery, and disrupted sleep, GH axis support is used as part of broader recovery protocols. The peptides are not targeting COVID biology specifically — they're addressing downstream consequences like impaired tissue repair and altered body composition.

See our Best Peptides for Muscle Growth guide for more on growth hormone secretagogues.

GLP-1 Agonists: An Unexpected Connection

One of the more surprising developments in long COVID research involves GLP-1 receptor agonists like Semaglutide and Tirzepatide. In September 2025, the NIH's RECOVER initiative selected tirzepatide as one of several drug candidates for long COVID clinical trials [21].

The rationale isn't just weight management. A physician at the Center for Complex Diseases reported treating over 350 long COVID patients with microdosed tirzepatide, observing 60-90% response rates for fatigue, brain fog, pain, and mast cell activation syndrome (MCAS) symptoms [21]. GLP-1 agonists have known anti-inflammatory properties and may reduce neuroinflammation, which could explain their apparent effects on long COVID symptoms beyond metabolic function.

Scripps Research is also planning a long COVID trial using tirzepatide, funded by the Schmidt Initiative for Long Covid, using a remote trial design with wearable devices and self-draw blood collection.

What the Evidence Supports (and What It Doesn't)

PeptideRelevance to Long COVIDHuman Clinical DataEvidence Level
Thymosin Alpha-1Immune restoration, T cell recoveryApproved in 35+ countries; in vitro PASC studyStrong for immune modulation; limited for long COVID specifically
SS-31Mitochondrial repair, fatigueFDA-approved for Barth syndrome (2025)Strong for mitochondrial dysfunction; no long COVID trials
BPC-157Tissue repair, gut healing, anti-inflammationThree published human studiesModerate; no long COVID-specific data
TB-500Vascular repair, systemic healingLimited human dataModerate preclinical; weak clinical
LL-37Antiviral (blocks Spike-ACE2), immunomodulationEarly oral LL-37 trial dataModerate; small clinical trials
Tirzepatide (GLP-1)Anti-inflammation, metabolic, brain fogNIH RECOVER trial in progressStrong for metabolic effects; long COVID trials underway
MOTS-cMitochondrial function, exercise mimeticNo human trialsPreclinical only
KPVAnti-inflammation, neuroinflammationLimitedPreclinical and clinical use

Being honest about what we know: No peptide has been proven to treat long COVID in large, randomized, controlled human trials. The NIH RECOVER trials now underway (testing tirzepatide and others) may change this, but results are not yet available. Most peptides used in current long COVID protocols are applied based on mechanistic rationale — they target pathways known to be disrupted in long COVID — rather than direct clinical evidence in PASC patients.

That distinction matters. Mechanistic rationale is not nothing. Thymosin Alpha-1 has decades of immune modulation data. SS-31 just received FDA approval for a mitochondrial condition. BPC-157 has 36 preclinical studies showing healing effects. But extrapolating from "this peptide improves mitochondrial function" to "this peptide will fix your long COVID fatigue" requires assumptions that haven't been validated.

Working With a Provider

If you're considering peptide therapy for post-COVID recovery, working with a knowledgeable healthcare provider is important for several reasons:

Diagnosis first. Long COVID symptoms overlap with thyroid disease, adrenal insufficiency, autoimmune conditions, and other treatable problems. Rule these out before attributing everything to long COVID.

Baseline testing. Before starting any peptide protocol, get comprehensive bloodwork: inflammatory markers (CRP, ESR, ferritin), immune panels (lymphocyte subsets, immunoglobulins), metabolic markers (fasting insulin, glucose, HbA1c), thyroid function, and a complete metabolic panel.

Start simple. A common clinical approach is to address the most prominent symptom cluster first rather than launching a multi-peptide protocol. If immune dysfunction appears primary, thymosin alpha-1 alone. If fatigue and exercise intolerance dominate, a mitochondrial-targeted approach. Stacking multiple peptides from day one makes it impossible to know what's helping and what's not.

Monitor and adjust. Repeat bloodwork at 4-6 weeks and every 8-12 weeks after. Track symptoms systematically — subjective improvements matter, but objective markers matter more.

Source quality. Use only peptides from licensed compounding pharmacies with certificates of analysis. Purity and potency issues are common with unregulated sources, and the last thing a recovering immune system needs is exposure to contaminants.

FAQ

Is there an FDA-approved peptide treatment for long COVID?

Not currently. The NIH RECOVER initiative is testing several drug candidates, including tirzepatide (a GLP-1/GIP agonist), but no peptide has received FDA approval specifically for long COVID. Thymosin Alpha-1 is approved in over 35 countries for other immune conditions, and SS-31 (elamipretide) was FDA-approved in 2025 for Barth syndrome.

Can peptides cure long COVID?

No single treatment has been shown to cure long COVID. Peptide therapy is one potential component of a broader recovery strategy that may also include pacing, sleep optimization, nutritional support, stress management, and treating any co-existing conditions. The goal with peptides is to support specific dysfunctional biological pathways rather than to "cure" a multifaceted condition.

How long does peptide therapy for post-COVID recovery typically take?

Protocols vary, but most practitioners report needing 8 to 16 weeks of consistent therapy before meaningful improvement. Some patients respond faster; others require longer protocols or changes in approach. Recovery from long COVID is rarely linear — expect fluctuations.

Are these peptides safe for people with autoimmune conditions?

This requires individualized medical judgment. Some peptides, like thymosin alpha-1, have immunomodulatory (balancing) rather than purely immunostimulatory effects, making them potentially suitable. Others that broadly activate immune responses could theoretically worsen autoimmune symptoms. Discuss your specific autoimmune condition and current medications with your provider before starting any peptide.

Can I take peptides alongside other long COVID treatments?

Many long COVID patients use peptides alongside other approaches — low-dose naltrexone, antihistamines for MCAS, mitochondrial supplements (CoQ10, NAD+ precursors, D-ribose), and others. Drug interactions with peptides are generally low-risk from a pharmacokinetic standpoint, but pharmacodynamic interactions (where one treatment changes how another works biologically) are possible. Full disclosure to your provider is non-negotiable.

What role does vitamin D play in peptide-based recovery?

Vitamin D directly regulates production of LL-37, the body's natural antimicrobial peptide. Adequate vitamin D levels (typically 40-60 ng/mL) support the body's own peptide-based defenses. Many long COVID patients are vitamin D deficient, and optimizing levels is considered a foundational step before or alongside peptide therapy.

The Bottom Line

Long COVID is a multi-system condition driven by immune dysregulation, mitochondrial dysfunction, chronic inflammation, and tissue damage. Peptides are being studied and used because they target these specific pathways — thymosin alpha-1 for immune restoration, SS-31 for mitochondrial repair, BPC-157 and TB-500 for tissue healing, LL-37 for antiviral support, and GLP-1 agonists for their unexpected anti-inflammatory effects.

The science behind why these peptides should help is often solid. The clinical evidence that they do help in long COVID patients is, with few exceptions, still catching up. The NIH RECOVER trials and ongoing research will eventually provide clearer answers.

In the meantime, peptide therapy for post-COVID recovery is best approached as one tool among many — used under medical supervision, guided by blood work and symptom tracking, sourced from reputable pharmacies, and paired with foundational interventions like sleep, nutrition, pacing, and stress management. The biology of long COVID is complicated. The recovery usually is too.

References

  1. Gupta A, Madan R, Bansal K. Mechanistic insights into Long Covid: viral persistence, immune dysregulation, and multi-organ dysfunction. Compr Physiol. 2025;15(3):e70019. doi:10.1002/cph4.70019

  2. SARS-CoV-2-specific CD8+ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years. Proc Natl Acad Sci USA. 2024;121(49):e2411428121. doi:10.1073/pnas.2411428121

  3. Michalak A, et al. Acute COVID-19 and Long COVID syndrome — molecular implications for therapeutic strategies. Front Immunol. 2025;16:1582783. doi:10.3389/fimmu.2025.1582783

  4. Molnar T, Lehoczki A, Fekete M, et al. Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches. GeroScience. 2024;46(5):5267-5286. doi:10.1007/s11357-024-01165-5

  5. Dominari A, et al. Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection. Int Immunopharmacol. 2023;118:110104. doi:10.1016/j.intimp.2023.110104

  6. Li Y, et al. Thymosin alpha 1 use in adult COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. PMC. 2022. PMC9754924.

  7. Liu J, et al. Thymosin alpha-1 has no beneficial effect on restoring CD4+ and CD8+ T lymphocyte counts in COVID-19 patients. Front Immunol. 2021;12:568789. doi:10.3389/fimmu.2021.568789

  8. Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250-1261. doi:10.1681/ASN.2012121216

  9. U.S. Food and Drug Administration. FDA approves elamipretide for Barth syndrome. September 2025. https://hub.jhu.edu/2025/09/25/fda-approves-barth-syndrome-treatment/

  10. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. doi:10.1016/j.cmet.2015.02.009

  11. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. doi:10.1038/s41467-020-20790-0

  12. Sikiric P, et al. Stable gastric pentadecapeptide BPC 157 — Robert's stomach cytoprotection/adaptive cytoprotection. Curr Pharm Des. 2018;24(18):2030-2040.

  13. Kang EA, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review. PMC. 2025. PMC12313605.

  14. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin beta4: a multi-functional regenerative peptide. Expert Opin Biol Ther. 2012;12(1):37-51.

  15. Wang C, et al. An in silico scientific basis for LL-37 as a therapeutic for COVID-19. PMC. 2021. PMC8441666.

  16. Vitamin D-inducible antimicrobial peptide LL-37 binds SARS-CoV-2 Spike and accessory proteins ORF7a and ORF8. Front Cell Infect Microbiol. 2025;15:1671738. doi:10.3389/fcimb.2025.1671738

  17. Antimicrobial peptide LL-37 increases rhinovirus-induced interferon beta expression in human airway epithelial cells through a Ca2+-dependent mechanism. PMC. 2025. PMC12226094.

  18. Zhao Y, et al. Efficacy and safety of oral LL-37 against the Omicron BA.5.1.3 variant of SARS-CoV-2: a randomized trial. J Med Virol. 2023;95(9):e29035. doi:10.1002/jmv.29035

  19. Teichman SL, et al. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295 in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805.

  20. Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561.

  21. NIH plans to test GLP-1s, other drugs for long COVID. Chemical & Engineering News. September 2025. https://cen.acs.org/pharmaceuticals/drug-development/NIH-plans-test-GLP-1s/103/web/2025/09