COVID-19 studies have neglected to focus on mucosal immunity, researchers argue

By Sarah MooreNov 27 2020Reviewed by Emily Henderson, B.Sc.

Researchers at the University of Buffalo (UB) suggest that COVID-19 studies should begin focusing on how mucous membranes in the mouth and nose develop immunity to the SARS-CoV-2 virus.

Image Credit: Cristian Moga/Shutterstock.com

According to the researchers, given that the virus is easily detected in the nose and mouth, the current body of research has neglected to explore the mucosal immune system, which is, by far, the immune system’s largest component. Future studies into this area will potentially be invaluable to preventative, diagnostic, and therapeutic advances in the fight against COVID-19.

Studies should refocus on the upper respiratory tract

In a paper published this month in the journal Frontiers in Immunology, the researchers at UB stress that the behavior of the mucosal immune system in relation to COVID-19 has not been thoroughly studied.

The paper’s senior author, Michael W. Russell, Ph.D., emeritus professor, Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB, highlights the issue, “We think it is a serious omission to ignore the mucosal immune response to SARS-CoV-2, given its initial sites of infection,”.

Clearly the response of the systemic immunoglobulin G antibody [the most abundant circulating antibody] is important - we do not deny that - but on its own it is insufficient.”

Initially, research focused on gaining further insight into how the virus descends to the lungs, which leads to the most severe cases of the infection. In the beginning, this made sense as it helps scientists understand how to possibly prevent these more life-threatening cases. Now, the UB researchers suggest, studies should be focusing on the upper respiratory tract.

Firstly, this is the location of the initial point of infection. Secondly, a high rate of asymptomatic transmission has been recorded, highlighting the need to understand the nature of immunity in the mucous membranes of the upper respiratory tract, as for many, the immune system is doing a good job of protecting them from the virus.

UB researchers theorize that early mucosal immune responses may be responsible for containing and eliminating the infection, resulting in a high percentage of people being asymptomatic.

A potential nasal vaccination

The paper’s researchers suggest that mucosal secretory immunoglobulin A (SIgA) antibody responses may help to explain the nature of the body’s response to COVID-19 infection. The difference between asymptomatic, mild, and moderate cases may be explained by differences in mucosal secretion. These differences may also vary depending on populations.

The paper explains that studies focussing on mucosal immunity may be essential to the development of a nasal vaccine, which is currently theoretical. However, if achieved, the development of such a vaccine would allow more people to have access to vaccination, given that current vaccinations are injected, and are required to be kept at special temperatures, making access to them more difficult in the developing world.

The team explains that a potential mucosal vaccine, particularly one that is intranasal, would theoretically be able to activate immune responses in the upper respiratory tract, the location where COVID-19 makes the first contact. Injected vaccines, on the other hand, do not normally do this.

To help a nasal vaccine become possible, the team at BU suggests that studies into the relationship between IgA antibodies and the disease stage of COVID-19 would be incredibly useful. Studies investigating the characteristics of cells known to secrete IgA antibodies induced by either infection or vaccination could also be invaluable.

In publishing their latest paper, the BU researchers hope to shine a light on these areas of study which have been neglected but may be vital to controlling the pandemic.