Solving a crime often leads detectives to interrogate those who were involved to uncover the truth. With each lead they follow, the once-foggy details come into sharper focus, painting a more accurate picture of the events that took place.
Scientists have been on the tail of SARS-CoV-2 viruses to solve how some infections can trigger severe symptoms, like cytokine storms, which cause patients to go into respiratory stress and multiorgan failure. Despite the recent surge of infections in younger populations, the mechanisms behind severe illness in this group—particularly in those who have no pre-existing medical conditions—remain elusive.
Although studies are investigating organ-specific immune responses, Laurent Rénia, a Senior Fellow and Principal Investigator at A*STAR Infectious Diseases Labs (ID Labs), emphasises the need to delve deeper into the resident cells to gain an accurate understanding of how the disease develops.
“If you know the mechanisms involved in lethal SARS-CoV-2, you can develop specific therapeutic approaches,” said Rénia.
Teaming up with Lisa Ng, Executive Director of ID Labs; Akhila Balachander and Subhra Biswas from A*STAR’s Singapore Immunology Network (SIgN); and other collaborators from the National Centre for Infectious Diseases and the Health Sciences Authority in Singapore, Rénia led a study that utilised a novel tissue profiling technique the team developed called iSPOT. The researchers analysed autopsy samples from five young patients who succumbed to COVID-19 despite having no underlying medical conditions.
“iSPOT is a multiplex approach that allows to look for multiple markers at once and also look for spatial interactions between different cells in a particular tissue,” explained Rénia.
This highly sensitive technique enabled the team to analyse the stromal cells that maintain organ architecture, immune cell populations and cytokine levels in the tissues of the lungs, heart and small intestine.
The researchers discovered that all patients had a lower immune cell count and that lung and small intestine tissues displayed significant structural damage. The lungs and heart showed severe hyperinflammation, with high levels of the cytokine tumour necrosis factor alpha (TNF-α) and varying levels of interleukin 6 (IL-6), interleukin 10 (IL-10), and interferon-gamma (IFN-γ) among the five subjects.
These findings highlight that combining different cytokine-targeting therapies can help control the cytokine storms and prevent fatal SARS-CoV-2 infections. Since their study, the team has patented the iSPOT technology and is currently refining it to better understand not only COVID-19 but also other diseases.
“The iSPOT technique is currently being improved by adding more immune and cell markers,” said Rénia. “This will allow us to refine the analyses for COVID-19 and other diseases such as cancer, where the mechanisms of immunopathogenesis remain poorly understood.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Infectious Diseases Labs (ID Labs) and the Singapore Immunology Network (SIgN).
