The analysis, published in the journal Frontiers in Immunology, noted that the mucosal immune system is the largest component of immunity, but hasn’t been a focus of much of the research on COVID-19 to date.
“We think it is a serious omission to ignore the mucosal immune response to SARS-CoV-2, given its initial sites of infection,” said Michael W. Russell, a co-author from the University at Buffalo in the US.
“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,” Russell added.
He said the initial focus of COVID-19 research was on cases of severe disease when the virus descends into the lower respiratory tract, especially the lungs.
In the lungs, the scientists said the cellular immune responses exacerbate the inflammation rather than fight the infection.
But since the upper respiratory tract, including the nose, tonsils and adenoids are the initial point of infection for the SARS-CoV-2 virus, they said the immune responses that are triggered there are of special interest.
The researchers believe the high rate of asymptomatic transmission of COVID-19 is another reason why mucosal immunity is so important.
“Given that many infected people remain asymptomatic, and that a large number of those who develop symptoms suffer only mild to moderate disease, this suggests that something, somewhere, does a fairly good job of controlling the virus,” said Russell.
The scientists called for more studies to determine the nature of mucosal secretory immunoglobulin A (SIgA) antibody responses over the course of infection — including those which are asymptomatic or pre-symptomatic — on both mild and moderate cases of COVID-19 disease.
They added that the mucosal immune responses may vary across different age groups and populations.
A focus on mucosal immunity might also make it possible to develop a type of vaccine, such as a nasal vaccine, that could be easier to store, transport and administer, the scientists noted.
Russell said these vaccines might not have special temperature requirements and might be more palatable for large swaths of the population, especially children, because they would not require an injection.
“The potential advantage of a mucosal vaccine is that it should induce immune responses, including SIgA antibodies, in the mucosal tracts, in this case especially the upper respiratory tract, where the coronavirus makes first contact,” explained Russell, adding that injected vaccines usually do not do this.
The researchers believe more molecular studies on IgA antibodies and their relationship to the disease stage of COVID-19 could shed more light on the unknowns.
“As mucosal immunologists with several decades of experience behind us, we have been perturbed at the lack of attention to this, and we hope to draw attention to this glaring omission,” said Russell.
“After all, the mucosal immune system is by far the largest component of the entire immune system, and it has evolved to protect the mucosal surfaces where the great majority of infections arise,” he added.