One of the most intriguing features of COVID-19 infection is the wide range of outcomes the disease is capable of causing—from no symptoms at all to severe pneumonia and acute respiratory distress syndrome, which can ultimately lead to death. The fast and furious COVID-19 research being performed around the world is revealing that an individual’s outcome is highly dependent on their immune system.
“As it is often the case for pathogenic infections, the host immune system is a key player in viral clearance and resolution of disease,” explained Lisa Ng, a Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), and Infectious Diseases Laboratories (ID Labs). “In this case, an imbalance between inflammation and protection leads to the progression to more severe disease.”
The problem is we still don’t know exactly which immune cells drive this progression. In early March 2020, Ng and a team of researchers, in collaboration with clinicians at the National Centre for Infectious Diseases in Singapore, began a search to find a marker of disease severity. Their study pointed to changes in specific subtypes of lymphocytes and neutrophils—two types of white blood cells.
Using a technique called high-dimensional flow cytometry, the researchers were able to efficiently study more than 50 types of immune cells in COVID-19 patients with varying symptoms in the early stages of the disease. They found that COVID-19 infection reduced the number of T cells expressing CD8 and VD2 proteins. Conversely, it increased the number of immature neutrophils, rather than total neutrophils as shown by other studies.
Noting that these patterns were more pronounced in severe cases, the researchers looked at the link between disease severity and the ratio of immature neutrophils to T cells expressing CD8 or VD2. They found that these ratios were both strong indicators and predictors of severe respiratory symptoms, with the ratio of immature neutrophils to VD2 T cells outperforming the ratio of total neutrophils to lymphocytes or CD8 T cells proposed by other studies.
“We hope that our findings will allow for rapid triage possibilities in heavily burdened hospitals,” said Ng, adding that the ratios can be used to predict whether a patient will develop severe COVID-19 symptoms, allowing them to receive early pre-emptive treatment if needed.
Ng and her team are now studying the immune systems of symptomatic and asymptomatic patients to identify potential differences. “Hopefully, this can help guide therapies and inform vaccine or treatment design,” she said.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN) and Infectious Diseases Laboratories (ID Labs) and the Infectious Disease Horizontal Technology Center.