March 11, 2025, marks five years since the World Health Organization (WHO) declared COVID-19 a pandemic. SARS-CoV-2, the virus which causes COVID-19, first surfaced in December 2019 in China. Global responses were quickly mobilized, and the full genomic sequence of SARS-CoV-2 (the building blocks that make the virus) was published online by scientists on January 10, 2020. This breakthrough set off a cascade of immunology research that was critical to the pandemic response, preventing the spread of the virus and saving lives. Five years on, we look at the impact immunology research had on the pandemic and what the future holds.
Monoclonal Antibody Therapy
Antibodies are proteins naturally produced by the immune system to fight pathogens, such as bacteria or viruses. Monoclonal antibodies (mAbs) are a type of antibody developed in a lab that stimulate the immune system. The first monoclonal antibody therapy was developed in 1986 and mAbs have been used to treat cancers and infectious diseases since.
Understanding the relationship between antibodies and viral infections, like SARS-CoV-2, informed the development of mAb therapies for COVID-19 patients. mAb therapies can block SARS-CoV-2 from attaching to human cells, making it difficult for the virus to cause disease. Most mAbs target the spike protein on SARS-CoV-2 and can be helpful to treat patients at risk of developing severe COVID-19, including hospitalization and death.
Knowing the genomic sequence of the spike protein specifically allowed researchers to test different mAbs in the laboratory. These experiments determined which mAb worked best against SARS-CoV-2. The best mAbs were then developed into treatments and studied in humans during clinical trials. As variants of SARS-CoV-2 continue to emerge, the effectiveness of mAbs can change. Ongoing research continues to identify the best mAb therapies for new and emerging SARS-CoV-2 variants.
mRNA Vaccines
Messenger RNA (mRNA) are molecules found in all life on earth that provide a way for the instructions in our genes (DNA) to be used to make specific proteins in our cells. In an mRNA vaccine, synthetic mRNA made in a lab carries instructions to tell your cells to build a protein that will induce an immune response. The research and technology that led to mRNA vaccines dates all the way back to mRNA’s discovery in1961.
From 1961 through the 1990s, scientists were uncovering how mRNA activates or blocks the building of proteins and how this could be used in medicines. A breakthrough came in 2005 when scientists discovered how to use mRNA to deliver instructions to cells in people. From 2005 to 2016, scientists studied how to use lipids (fats) as protective envelopes to deliver mRNA to cells in humans. When in 2013 scientists discovered the structure that allowed viruses to invade cells, they had the puzzle pieces necessary to build mRNA vaccines.
Early research applications of mRNA vaccines included RSV, Zika virus, Nepah virus, and Ebola. In 2016, scientists applied the research on mRNA vaccines to create a Middle Eastern Respiratory Virus (MERS) vaccine. MERS is a type of coronavirus like SARS-CoV-2. These decades of research on mRNA and the immune system culminated in the ability to easily use the SARS-CoV-2 spike protein in mRNA vaccines for the COVID-19 pandemic response. Studying COVID-19 mRNA vaccines is further advancing our understanding of their applications. This research is now opening the door for new vaccines to treat other diseases like HIV, Hepatitis B, and herpes.
Long COVID
Following COVID-19 disease, some patients experience symptoms for weeks or months, a condition called long-COVID. A lot about long-COVID is not fully understood, but researchers are working hard to understand the causes and develop potential treatments. Multiple studies have identified that women are more likely to develop long COVID than men. Continuing this research to understand the sex-based differences in risk and symptoms of long COVID can help to guide future diagnosis and treatments. The Listen to Immune Symptom and Treatment Experiences Now (LISTEN) Study at the Yale School of Medicine intends to understand long COVID symptoms and immune responses in adults to identify potential therapies for people living with these conditions.
In addition to understanding long COVID itself, researchers are investigating the similarities between long COVID and other long-lasting diseases that occur after viral infection. The symptoms of long-COVID overlap with conditions such as fibromyalgia and post-treatment Lyme disease syndrome inspiring immunologists to investigate how the immune system may act similarly to cause these conditions.
The Power of Immunology Research
Over the last five years, immunology research has not only impacted on the COVID-19 response but also increased our understanding of the immune system. New technologies and new information gleaned from the pandemic can now be applied beyond COVID-19, progressing science and changing lives in areas like cancer and chronic disease. Immunologists have played an integral part to this important research that unravels the interactions between the body’s immune response, viral infections, and more.
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