As COVID-19 began to surge five years ago, no one knew what to expect.
Neither did the immune system.
Confronted with a new virus, humanity was immunologically naive. The emergence of SARS-CoV-2 provided a rare opportunity to study the immune system in action, and researchers raced to gather all the data they could. “The world was exposed to a brand-new pathogen,” says Nadia Roan, an immunologist at the University of California, San Francisco. “We were trying to leverage that to learn more about immunity.”
Years later, scientists are still approving knowledge to obtain greater understanding of how the immune formula works. There are 4 classes that have learned so far.
At the beginning of the pandemic, many researchers turned to antibodies produced in reaction to SARS-CoV-2 infection. Like antibodies, immune parts called T cells also fight infection, but they first drew attention. Many clinical trials of COVID-19 vaccines, for example, have looked at degrees of antibodies and T cells.
That’s in part because T cells are more difficult to study than antibodies, and so our understanding of them has lagged, says Shane Crotty, an immunologist at the La Jolla Institute for Immunology in San Diego, California.
As the pandemic continued, it has become clear that T cells were an arm of the immune reaction to the SARS-CoV-2 and CoVVI-19 vaccines, explains Alessandro Satede, also an immunologist at the La Jolla Institute of Immunology. Antibodies opposed to SARS-CoV-2 declined in the months following vaccination, but other vaccinated people continued to make T cells that identified the virus1. This coverage of T lymphocytes remained strong, Settte et al. discovered 2, even opposite to viral variants that dodged antibody defenses raised through the first generation of tin vaccines.
“People used to focus more on antibodies, and tended to forget about the T-cell responses,” says Rosemary Boyton, an immunologist at Imperial College London. “Now we understand much, much better that the T-cell responses matter as well.”
The pandemic also gave researchers new insights into the innate immune system, another line of defence against viruses.
Innate immune reactions are not as express as antibodies and T-mobiles. Cells can release those reactions when they stumble upon foreign molecules, such as the SARS-CoV-2 RNA genome. When a mobile phone discovers a telltale molecule, it raises the alarm, by releasing proteins called interferons. These proteins activate gene loads, many of which are concerned with viral defense. The interferon reaction also warns that other cells in the same organ are on higher alert, explains Benjamin Tenoever, a virologist at New York University in New York. “It can be very overwhelming for a virus. “
Children and Covid: Why Young People Immune Systems on Top
Before the pandemic, the idea of the researchers that this scream of caution did not travel much beyond the infection site. But when Tenoever and his colleagues analyzed samples of hamsters and autopsies of other people who had been inflamed before through the SARS-COV-2, discovered symptoms of interferon reactions in the body, even in organs far from inflamed cells 3. Later, the team learned that this is not limited to SARS-COV-2: the influenza virus also reason a generalized interferon reaction to hamsters.
The tenuous mortgage that those global antiviral defenses decorate the coverage in case the infection moves through the body. It may also be a component of the explanation why SARS-CoV-2 variants that spread later in the pandemic are less likely than their predecessors to cause severe disease: Later variants attached more than the virus’s previous bureaucracy to cells in the nose, keeping the virus in the upper respiratory tract longer. This allowed the innate caution sign to succeed in the lungs and strengthen defenses there before the virus arrived.
Before the pandemic, researchers weren’t very interested in the nose, says Jose Ordovas-Montañes, an immunologist at Boston Children’s Hospital in Massachusetts. “It’s the idea to just be a passive tube to get air into the lungs,” he says. “And. The lungs were where the company happened. “
Pandemia has highlighted the importance of understanding immune responses in express tissues, and especially where infection begins: nose.
The moist lining of the nose is a unique immune environment that contains a different blend of antibodies and immune cells to that found in the blood. As a result, injected vaccines, which generate antibodies in the bloodstream, might not be ideal for blocking infection in the nose. “One of the lessons from the pandemic is location, location, location,” says Crotty.
DOI: https://doi. org/10. 1038/d41586-025-00128-w