COVID-19: Why We Need More Than Just the Vaccine

Edahiro, R., Shirai, Y., Takeshima, Y. et al. Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity. Nat Genet 55, 753–767 (2023). https://doi.org/10.1038/s41588-023-01375-1

One of the key challenges of the COVID-19 virus is its wide ranges of severities, from asymptomatic infection to fatal failure of the respiratory system and organs. While the COVID-19 vaccines have helped to fight the pandemic through prevention of spread, there is still a great need for treatments for severe COVID-19 infections.

Using a type of analysis called single-cell-RNA-sequencing researchers found that problems with creating an effective immune response in blood circulating in the body (peripheral blood) impacted the severity of COVID-19 infection. Additionally, an uncontrolled interferon response can lead to a more severe COVID-19 infection. Interferons are substances that help the immune system battle infection, which is why when it is unregulated, the push to fight off disease may not be strong enough, leading to more severe infection. Additionally, the number of T cells (type of white blood cell), B cells (type of protein), monocytes (a type of white blood cell), antigen-presenting cells (cells that process antigens, molecules that trigger an immune response), and natural killer cells (a cell that can kill cancer cells and other sick cells) in the body also affect the severity of infection.

When analyzing COVID-19 patients, it was found that an immune cell called nonclassical monocytes decreased in number. Also, the switch from classical monocytes to nonclassical monocytes also decreased. Classical monocytes create an initial inflammatory response whereas the nonclassical conocytes are anti-inflammatory. As the nonclassical monocytes decrease, the body is more subject to infection due to the presence of less white blood cells. As a result, COVID-19 becomes more severe in these cases. In fact, according to the genome-wide-association-studies, genes were now linked to the development of COVID-19. In particular, the gene named IFNAR2 impacted the gene expression occurring in monocytes, preventing it from producing its protein.

In a separate study on COVID-19, the trend seen was increasing B cells and plasmablasts (an early antibody response) while it was decreasing in severe COVID-19 infection. When dysregulated interferon response occurs, there are less interferons answering the call for help from the immune system, making the innate immune cells crucial since they help fight off diseases. Overall, in an experiment of nearly 7,000 neighborhoods, around 1,000 reported significant data in which there was measurable levels of B cells and plasmablasts. The amount of nonclassical monocytes and classical monocytes both decreased, more often in cases of moderate to severe COVID-19.

Overall, more research still needs to be conducted about new medicines that can help treat severe COVID-19 past just the vaccine. However, recent research on genetics is helping answer some of the questions needed to find better treatment, such as why COVID-19 can be more severe in some cases than others.

By Jeannine Yu