A group of volunteers in the UK let scientists put the SARS-CoV-2 virus up their noses for research investigating why some of us naturally avoid getting COVID-19. This first-of-its-kind study opens the door to better vaccines and treatments.
While there have been plenty of studies examining everything from the mental to the physiological effects of COVID-19 on infected patients, there hasn't been any research that tracked the course of the disease from the moment the SARS-CoV-2 virus enters a person's nose to the development of illness. That has now changed with newly published research led by University College London (UCL).
Called the UK COVID-19 Human Challenge study, the research deliberately infected 36 healthy, young, willing adult volunteers through their noses with the COVID-causing virus. All of the volunteers were screened for the risk of severe disease and potential comorbidities prior to the study and were given the lowest-possible dose of SARS-CoV-2 that was still able to cause infection.
“Human challenge models are an invaluable way to build our understanding of how the body responds to infectious disease," said Shobana Balasingam, research lead in Wellcome's Infectious Disease team, who also participated in the research. "These studies enable us to closely monitor what happens from the moment of infection by allowing us to follow the immune response through to the development and severity of symptoms."
After infecting the participants, the researchers immediately began monitoring the cells in their blood and nasal linings to see what happens the instant after exposure to the virus. This detailed analysis led to a dataset of over 600,000 individual cells, which have become part of an effort to create a comprehensive reference map of all human cells known as the Human Cell Atlas.
The nose knows
In all of the participants, the researchers found that specialized mucosal immune cells in the blood were activated along with a reduction in inflammatory white blood cells whose role is typically to surround and destroy pathogenic invaders.
But in the participants who immediately cleared the virus and resisted infection, or in those who tested positive but avoided a full systemic infection, they witnessed what they described as a never-before-seen immune response.
In particular, they found high background activation of a gene called HLA-DQA2, which is a kind of first-alert system that signals the presence of a viral invader to other cells. They also found that in those who best resisted the virus, there was a quicker immune response in specialized nasal cells and a slower response in blood cells, versus those who became infected. The group that contracted COVID-19 only mounted a nasal response after five days of viral exposure, indicating that activation of these nasal cells could be a critical pathway for fighting this and potentially other coronaviruses.
Additionally, the researchers also found recurring patterns in amino acids among activated T cell receptors, the cells in the body that can target and eliminate infected cells in the body. These amino acid patterns are known as motifs.
The fact that these motifs recurred in response to pathogen exposure suggests they share the ability to recognize something in the SARS-CoV-2 virus. Identifying these motifs gave the researchers the opportunity to model the interaction between TCRs and a pathogen. The findings could help them engineer virus-specific T cells for treatment not just for COVID-19, but also potentially for a range of diseases that involve immune attack.
Marko Nikolić, senior author of the study at UCL, echoes the hope that the team's research will lead to better ways to attack pathogens in our bodies.
“These findings shed new light on the crucial early events that either allow the virus to take hold or rapidly clear it before symptoms develop," he said. "We now have a much greater understanding of the full range of immune responses, which could provide a basis for developing potential treatments and vaccines that mimic these natural protective responses.”
The research has been published in the journal Nature.
Source: Wellcome Sanger Institute
