Study Reveals Why Mild COVID-19 Infections May Not Train the Immune System Effectively
Nikhil Prasad Fact checked by:Thailand Medical News Team May 11, 2025 20 hours, 33 minutes ago
Medical News: A fascinating new study out of South Korea has uncovered how previous infections with common cold viruses may help protect people from severe COVID-19—but with a hidden cost. Researchers discovered that people who had only mild COVID-19 tend to develop CD4+ T cells that respond weakly to the virus’s membrane (M) protein. This
Medical News report highlights how such a muted response could influence long-term immunity and pandemic preparedness.
Study Reveals Why Mild COVID-19 Infections May Not Train the Immune System Effectively
The study was conducted by a collaborative team from multiple top-tier Korean institutions, including the Korea Virus Research Institute at the Institute for Basic Science (IBS), the Korea Advanced Institute of Science and Technology (KAIST), the Samsung Medical Center, Korea University Ansan Hospital, Severance Hospital at Yonsei University, and Chungbuk National University College of Medicine.
The Role of T Cells and Pre Existing Immunity
CD4+ T cells are a type of immune cell that helps the body fight off viruses by coordinating the immune response and producing protective proteins. The researchers focused on a protein called the M protein from SARS-CoV-2, the virus responsible for COVID-19. Surprisingly, they found that even people who had never been infected with COVID-19 before still had T cells that reacted to this M protein. This hinted that past infections with common cold coronaviruses (known as CCCoVs) might have prepared their immune systems in advance.
When the researchers looked deeper, they confirmed that the T cells in unexposed individuals were indeed activated by CCCoV M proteins but could also “cross-react” with SARS-CoV-2’s M protein. While this cross-immunity might help these individuals experience milder symptoms, it turned out that the T cells generated were not very strong in their response—a concept called “low functional avidity.”
Weak Memory Response Found in Mild COVID Cases
To explore the strength of these T cell responses, the study measured how much virus protein was needed to trigger an immune reaction. The findings showed that people who recovered from mild COVID-19 had weaker T cell responses compared to those who had more severe disease. Their immune systems could still recognize the virus, but the reaction was much less robust, suggesting that their immune “memory” might not be as protective in future encounters.
Importantly, this weaker T cell response was similar to what was seen in people who had never had COVID-19—indicating that the immunity formed during mild illness may be as feeble as the residual cross-reactivity from common cold infections.
Implications for Immunity and Future Pandemics
These findings provide indirect but important evidence that prior infection with common cold viruses might offer some level of protection from COVID-19. However, the cost of this “quick response&rdquo
; is that the resulting immune memory is less effective. In contrast, individuals who suffered more severe disease likely generated stronger, more specific immune responses that could better protect them in the future.
The study emphasizes that while some immunity from previous coronavirus exposures can be beneficial, it may not always result in long-lasting or high-quality protection. This insight is vital for future vaccine design, especially as the world faces the possibility of new and emerging coronavirus strains.
Conclusion
The research offers a nuanced view of immunity to SARS-CoV-2, showing that not all immune responses are created equal. Those who develop COVID-19 after having pre-existing immunity from common cold coronaviruses might avoid severe symptoms but could end up with weaker long-term protection due to the low functional avidity of their T cells. This could make them more vulnerable to reinfection or to complications from variants in the future. Understanding these immune dynamics is critical not just for managing COVID-19 but also for preparing for the next potential pandemic.
The study findings were published in the peer reviewed journal: Immune Network.
https://immunenetwork.org/DOIx.php?id=10.4110/in.2025.25.e4
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