Thread by @polybioRF

BREAKING: PolyBio-supported study reveals long-term immune and metabolic damage after COVID-19 infection

New preprint study reveals profound & long-lasting biological disruptions that can follow a SARS-CoV-2 infection, i.e. changes connected to altered metabolism & cancer-associated epigenetic changes

polybio.org/polybio-suppor…

2/ New research published by scientists from the University of California San Francisco reveals that COVID-19 can lead to significant and enduring alterations in the immune and metabolic systems of impacted individuals.

3/ Some of these changes may underlie the persistent symptoms experienced by many post-COVID-19 patients (Long COVID). The research was supported in part by PolyBio Research Foundation via the LIINC program.

polybio.org/projects/liinc…

4/ The study, conducted roughly four months after initial infection, identified widespread metabolic abnormalities in individuals with prior COVID-19.

5/ These included dramatically reduced levels of tryptophan (an essential amino acid important for immune and neurological health), persistent elevation of pro-inflammatory lipid mediators, and methylation changes in genes tied to metabolism.

6/ Notably, potentially-harmful inflammatory lipids like arachidonic acid were elevated, while beneficial ones such as AEA and DHEA—linked to cardiovascular and brain health—were decreased.

7/ These findings suggest that targeting lipid pathways through interventions like omega-3 supplementation or metformin may help mitigate symptoms and prevent further damage.

8/ Immune alterations

On the immune front, the researchers observed a state of ongoing inflammation, including persistent activation of peripheral immune cells and systemic oxidative stress.

9/ The blood of Long COVID patients showed a shift toward immature myeloid cell types—commonly seen in chronic inflammatory diseases—suggesting prolonged immune dysregulation.

10/ Notably, IL-1β, a powerful pro-inflammatory cytokine, was elevated in those with Long COVID, which may be driving continued production of these immature immune cells.
Crucially, signs of immune system aging—or senescence—were also found.

11/ T-cells, particularly CD8 cells responsible for killing infected cells, showed markers of exhaustion and poor function. These included increased expression of aging-related genes such as p16INK4a and KIRs, and elevated levels of suPAR,

12/ (cont.) a blood marker linked to chronic inflammation and poor immune resilience. These findings parallel patterns seen in chronic infections like HIV, which are known to deplete effective immune surveillance.

13/ The authors note that persistent SARS-CoV-2 reservoirs, reactivation of latent viruses like Epstein-Barr virus, and damage to the gut barrier may all contribute to this pro-inflammatory and dysregulated metabolic cascade.

pubmed.ncbi.nlm.nih.gov/39947217/

14/ Treatments aimed at reducing oxidative stress, modulating the immune system, and addressing viral persistence—such as the use of mTOR inhibitors or antiviral therapies—may offer new therapeutic avenues.

15/ Indeed, PolyBio is supporting a clinical trial of mTOR inhibitor rapamycin in Long COVID, the results of which will further to shed light on how drugs impacting metabolic health and pathogen hijacking of mitochondrial function may benefit patients with post-COVID chronic symptoms.

16/ Post-COVID epigenetic changes and cancer risk

The study findings also raise concerns that COVID-19 may increase the long-term risk of cancer by disrupting the normal regulation of genes involved in tumor growth and immune function.

17/ Specifically the researchers found that people who had recovered from COVID-19 showed lower levels of DNA methylation—a chemical process that helps regulate gene activity—at specific genes linked to cancer development, compared to those who had never been infected.

18/ Reduced methylation typically means those genes are more active.
Notably, genes like ZFP64p1 and CBR3-AS1, which are known to drive the development of multiple cancers and inflammatory conditions, were less methylated in the post-COVID group.

19/ ZFP64p1 is a transcription factor that boosts expression of several cancer-related genes, making tumors more resistant to immune responses. CBR3-AS1 is a long non-coding RNA linked to both cancer and autoimmune diseases.

20/ In contrast, individuals who had not had COVID-19 showed higher methylation—suggesting more stable silencing—of tumor-promoting genes. This imbalance hints at a possible epigenetic “reprogramming” following SARS-CoV-2 infection.

21/ The researchers note that SARS-CoV-2 proteins have been previously shown to degrade key tumor suppressors like p53. Combined with the long-lasting effects of inflammation, immune dysregulation, and stress after COVID-19,

22/ (cont.) this could potentially set the stage for increased cancer risk in the months or years following infection. Overall the findings emphasize an urgent need for more research aimed at studying the impact of persistent SARS-CoV-2 infection on cancer development.

23/ A donation to PolyBio from the Chan Soon-Shiong Family Foundation is moving further research on the topic forward, including via the UCSF Long COVID LIINC study.

24/ On X, Dr. Patrick Soon Shiong MD wrote an articleemphasizing the seriousness of the UCSF preprint findings, including the need for global investment in treatments to improve immune function in post-COVID individuals.

https://x.com/DrPatSoonShiong/status/1913378215462068320