Differing immune responses in varying COVID-19 cases, study finds

A new study in the United Kingdom identified differences in the immune response to the novel coronavirus (COVID-19), between people with no symptoms compared to those suffering a more serious reaction to the virus, according to research published in the journal Nature Medicine.

For the study, researchers from the Wellcome Sanger Institute, Newcastle University, University College London, University of Cambridge, EMBL's European Bioinformatics Institute, and their collaborators within the Human Cell Atlas initiative, analyzed blood from 130 people with COVID-19. These patients came from three different U.K. centers, Newcastle, Cambridge, and London, and ranged from asymptomatic to critically severe.

The team performed single-cell sequencing from roughly 800,000 individual immune cells, along with detailed analysis of cell surface proteins and antigen receptors found on immune cells in the blood. They revealed differences in multiple types of immune cells that are involved in the body's response to COVID-19.

The COVID-19 pandemic has caused millions of deaths and many more infections worldwide. Symptoms vary widely in severity and can range from a mild cough to severe respiratory distress, blood clots and organ failure. Several previous studies have highlighted a complex immune response in the blood, but the full coordinated immune response and how this differs between symptomatic and asymptotic patients had not been investigated in detail.

In those with no symptoms, the researchers found increased levels of B cells that produce antibodies that are found in mucus passages, such as the nose. These antibodies may be one of our first line of defense in COVID-19. However, these protective B cells were missing in people with serious symptoms, indicating the importance of an effective antibody-associated immune response at the nose and other mucus passages.

The researchers also discovered that whereas patients with mild to moderate symptoms, had high levels of B cells and helper T-cells, which help fight infection, those with serious symptoms had lost many of these immune cells, suggesting that this part of the immune system had failed in people with severe disease. In contrast, people with more serious symptoms leading to hospitalization had an uncontrolled increase in monocytes and killer T-cells, high levels of which can lead to lung inflammation. Those with severe disease also had raised levels of platelet-producing cells, which help blood to clot.

The researchers found raised levels of specific immune cells in asymptomatic people. They also showed people with more serious symptoms had lost these protective cell types but gained inflammatory cells. These differences in the immune response could help explain serious lung inflammation and blood clotting symptoms and could be used to identify potential targets for developing therapies, the researchers said.

While it is not yet understood how the infection stimulates these immune responses, the study gives a molecular explanation for how COVID-19 could cause an increased risk of blood clotting and inflammation in the lungs, which can lead to the patient needing a ventilator. This also uncovers potential new therapeutic targets to help protect patients against inflammation and severe disease. For example, it may be possible to develop treatments that decrease platelet production or reduce the number of killer T-cells produced, however more research is required.

In the future, the authors said research may identify those who are more likely to experience moderate to severe disease by looking at levels of these immune cells in their blood.

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