Even Mild or Asymptomatic COVID-19 Infections Leave Over 700 DNA Methylation Changes After Recovery!
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 20, 2025 8 hours, 37 minutes ago
Medical News: In a groundbreaking study that could change how we view the long-term impacts of COVID-19, researchers from Germany have discovered that even mild or asymptomatic infections with SARS-CoV-2 can lead to lasting molecular changes in human DNA. These changes remain detectable for months after the initial infection has resolved, offering new insight into the hidden effects of the virus on our biology.
Even Mild or Asymptomatic COVID-19 Infections Leave Over 700 DNA Methylation Changes After Recovery!
The study was led by scientists from Helmholtz Zentrum München, Ludwig-Maximilians-Universität (LMU) Munich, the German Center for Cardiovascular Research, the German Center for Infection Research, the Fraunhofer Institute for Translational Medicine and Pharmacology, and the University Hospital LMU Munich. Their findings are part of the large-scale ORCHESTRA study supported by the European Union and German institutions.
While many think of COVID-19 as a short-term illness, this
Medical News report highlights that its reach may extend far beyond fever and cough. By studying 346 individuals over a span of seven months, the researchers found changes in DNA methylation—a crucial biological mechanism that controls how genes are switched on or off—among those who had recovered from mild or even asymptomatic COVID-19.
COVID-19 Leaves Lasting Marks on DNA
DNA methylation is like a volume knob for your genes. It doesn’t alter your genetic code, but it changes how your body reads it. This process is essential for normal development and disease prevention, but it can also be disrupted by viral infections. Researchers found that COVID-19 infection can significantly alter this methylation process, leaving behind a unique molecular fingerprint long after the virus is gone.
To uncover these patterns, the team used advanced technology to scan over 690,000 genetic markers in blood samples from people who had either been infected or were confirmed as never infected. Importantly, the study focused on mild and asymptomatic cases—groups that are often overlooked in COVID-19 research. Despite their seemingly minor symptoms, these individuals still showed measurable epigenetic changes, indicating the virus may affect nearly everyone it infects at the molecular level.
Molecular Traces Linked to the Immune Response
One of the most important discoveries was the identification of two specific DNA markers—called CpG sites—named cg17126990 and cg25483596. These were consistently altered across all patients who had been infected, regardless of whether their infection was confirmed through PCR tests or antibody presence.
The first marker, cg17126990, is linked to a gene known as AFAP1L2. This gene plays a role in immune signaling pathways and has been shown in previous studies to become more active after SARS-CoV-2 infection. The second, cg25483596, is associated with the PC gene, which regulates key processes in cellular metabolism—som
ething that viruses like SARS-CoV-2 are known to hijack.
These epigenetic changes were found not only in people who tested positive for the virus but also in those who had persistent health symptoms long after infection—suggesting a molecular basis for what many now call Long COVID.
More Than 700 Epigenetic Alterations Detected
Across three distinct models of analysis, the researchers identified hundreds of changes in DNA methylation:
-42 CpG sites linked directly to the level of COVID-19 antibodies in the blood
-172 altered sites based on antibody-positive individuals
-502 different sites found in individuals who had tested positive by PCR
Some of these changes were linked to genes involved in inflammation, metabolism, and immune function, showing how the virus might reprogram the body’s response at a very deep level.
Notably, the study also analyzed DNA methylation in people who reported persistent health problems after infection. In this group, 40 CpG sites were found to be differentially methylated, further supporting the idea that Long COVID symptoms have a biological foundation, not just psychological or social roots.
Genetic Factors May Influence Long-Term Effects
Some of the altered DNA sites identified in the study were influenced by nearby genetic variants, known as methylation quantitative trait loci (meQTLs). This suggests that a person’s unique genetic makeup may partly determine how their body’s DNA responds to the virus—and how likely they are to experience long-term symptoms.
Among the significant genes affected were:
-
GIPR: linked to inflammation markers like C-reactive protein
-
PIK3C2B: associated with lung function
-
ITPKA: involved in calcium signaling and linked to respiratory disease
These findings could pave the way for personalized treatments and diagnostics based on a person’s genetic and epigenetic profiles.
Long-Term Molecular Memory of the Virus
Perhaps most striking is the fact that these molecular changes were still detectable seven months after infection. This provides strong evidence that COVID-19 creates a long-lasting "memory" in our cells—even in those who experienced only mild symptoms or no symptoms at all.
These results stand apart from earlier research, which mostly focused on severely ill patients. In contrast, the current study shows that subtle biological disruptions can happen quietly in the background, raising concerns about the long-term health implications for millions of people globally who were never hospitalized or formally diagnosed.
A Wake-Up Call for Post-COVID Monitoring
The study also raises questions about whether some of these changes might contribute to future disease risk. For instance, changes in genes involved in metabolism or immune regulation could potentially influence vulnerability to other infections, autoimmune conditions, or chronic inflammation down the line.
While it’s still too early to say how permanent these changes are, this research opens the door to future investigations into how COVID-19 may silently increase long-term health risks for many people.
Conclusions
This pivotal study highlights the unseen molecular scars left behind by SARS-CoV-2, even in people with mild or asymptomatic infections. Researchers identified hundreds of changes in DNA methylation patterns that can influence gene expression and immune responses. Two key CpG markers—cg17126990 in the AFAP1L2 gene and cg25483596 in the PC gene—stood out across all models, suggesting they may be central to how the body responds to the virus. These findings not only validate the existence of post-COVID biological changes in people who may not even realize they were infected, but also offer a potential roadmap for identifying and treating Long COVID. Moving forward, such molecular insights could help shape public health strategies and clinical management of post-COVID syndromes by identifying at-risk individuals before symptoms even appear.
The study findings were published in the peer reviewed journal: Clinical Epigenetics
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-025-01866-4
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https://www.thailandmedical.news/news/study-reveals-that-covid-19-alters-key-human-genes
https://www.thailandmedical.news/news/breaking-hypothesis-that-majority-exposed-to-sars-cov-2-will-have-shortened-lifespans-validated-by-study-showing-nsp2-impairs-human-4ehp-gigyf2-comple
https://www.thailandmedical.news/articles/coronavirus
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