Researchers from the Wellcome Sanger Institute, University College London, and the Netherland Cancer Institute studied immune responses against SARS-CoV-2. The results showed that not all exposed participants developed a COVID-19 infection which uncovered the unique immune responses associated with resisting sustained viral infection and disease.
While COVID-19 could be fatal, many will come into contact with someone who has tested positive, but avoid getting ill themselves (either negative on PCR testing or having an automatic response.)
I remember back in 2020, I got COVID-19 and my symptoms were severe. However, despite spending long hours with me on vacation, both my dad and brother never tested positive.
In the study, 36 healthy adult volunteers without a previous history of COVID-19 were administered SARS-CoV-2 through the nose. The researchers studied the blood and nasal lining of 16 volunteers to track how their bodies responded to the virus. They used a method called single-cell sequencing to analyze more than 600,000 cells. The team found new immune system reactions that happen as soon as the virus is detected. This included activation of specialized mucosal immune cells in the blood and a reduction in inflammatory white blood cells that normally engulf and destroy pathogens. 
Individuals who immediately cleared the virus did not show the typical widespread immune response but instead a never-seen-before innate immune response. In AP Biology, we learned that innate immune response is the first line of defense in the body. In other words, it is active immediately upon infection.
Researchers think that the high activity of a gene called HLA-DQA2 before exposure helped these people stop the virus from causing a long-lasting infection. According to the National Library of Medicine, the HLA-DQA2 gene is located in intracellular vesicles and plays a critical role in releasing Class II molecules from the peptide binding site. Class II molecules are expressed in antigen-presenting cells and “are used to present antigenic peptides on the cell surface to be recognized by T-cells.” How do you think the discovery of the HLA-DQA2 gene’s role in immune response could influence future treatments for COVID-19 or other infections?
However, six people had a longer-lasting SARS-CoV-2 infection. They showed a fast immune response in the blood, but their immune system was slower to respond in the nose, which allowed the virus to take hold there.
The researchers further identified common patterns among activated T cell receptors. In AP Biology, we learned T-cells recognize and bind to virus-infected cells and trigger a cell-mediated response. In this case, T-Helper cells stimulate other T cells to divide and create either T-memory or T-Killer cells. T-memory cells help prevent reinfection, and T-killer cells kill infected or cancerous cells. These findings offer insight into immune cell communication and the potential for developing targeted T-cell therapies against other diseases besides COVID-19.
For instance, an article from the Massachusetts Institute of Technology(MIT) describes researchers using a vaccine that boosts the response of engineered T cells, known as chimeric antigen receptor (CAR) T cells, and also helps the immune system generate new T cells that target other tumor antigens. “This vaccine boosting appears to drive a process called antigen spreading, wherein your own immune system collaborates with engineered CAR T cells to reject tumors in which not all of the cells express the antigen targeted by the CAR T cells,” says Darrell Irvine, the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and of Materials Science and Engineering.
Dr. Sarah Teichmann, the lead researcher and co-founder of the Human Cell Atlas, explained that by creating the Human Cell Atlas (a large-scale scientific project aimed at mapping and understanding the different types of cells in the human body), we can better understand which cells in our body are key for fighting infections. This will also help explain why people react differently to COVID-19. In the future, researchers can use this reference data to compare how the body’s natural immune response to a new virus is different from the response triggered by a vaccine.
I find it fascinating how each of our immune systems reacts differently to a virus like COVID-19. Personally, knowing how complex our immune responses are reinforces how vital continued research is in preparing for and combating future pandemics. Have you or anyone you know experienced unusual immune responses to COVID-19?
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