PERTH, Australia – Researchers at the QIMR Berghofer Medical Research Institute in Queensland have developed a way of testing whether COVID-19 patients’ immune systems are gearing up to fight the virus that causes the disease.
The discovery could be used to identify early on which patients’ immune systems are not responding appropriately, and who might be at higher risk of becoming sick.
The findings, which were published Dec. 7, 2020, in the journal Clinical & Translational Immunology, provide a monitoring approach “for identifying SARS-CoV-2 cellular immunity and may serve as a diagnostic for the stratification of risk in immunocompromised and other at-risk individuals,” study authors said.
The prototype test detects high levels of two key chemical signals that are produced by T cells when they recognize SARS-CoV-2-infected cells and start to fight the infection.
T cells typically mount an early response even before the body starts to produce antibodies. Importantly, T cells develop a lasting memory of viral infections, enabling the immune system to respond rapidly in the event of reinfection.
Researchers examined blood donated by 44 Queenslanders who had recovered from COVID-19, said Corey Smith, study leader and the head of QIMR Berghofer’s Translational and Human Immunology Group. The goal was to find out which combination of viral peptides could be used to stimulate T cells in the lab and allow researchers to measure their response to SARS-CoV-2.
“T cells produce a range of signaling molecules when they fight viruses,” Smith said. “These signaling molecules are basically indicators of whether T cells are responding to the SARS-CoV-2 virus and are mobilizing the immune army to launch an attack.
“If we can find a way to detect whether or not they are present, then we can find out whether or not a patient’s immune system is responding as it should.”
The scientists isolated the T cells from the donated blood, exposed them to viral peptides, and measured the production of a number of different signaling molecules.
They then compared the levels produced by T cells from recovered COVID-19 patients with levels released by T cells from 20 healthy donors who had never been infected with SARS-CoV-2.
The researchers found that T cells from people who had recovered from COVID-19 produced larger amounts of the signaling molecules interferon gamma and interleukin-2, which are involved in killing virus-infected cells and encouraging other T cells to fight infection.
They then screened a range of SARS-CoV-2 peptides “to work out which combination could be used to detect a successful T cell immune response, which we can then measure by detecting these two key signaling molecules,” Smith said.
More than 67 million cases of COVID-19 have been reported worldwide, and the disease has caused more than 1.5 million deaths, according to Johns Hopkins University data. In Australia, 908 people have died from the disease, and there have been more than 27,970 reported infections.
Although Australia has been successful in controlling infection rates, a blood test for early immune response to the virus could help other countries experiencing second and third waves, said Katie Lineburg, one of the QIMR Berghofer researchers.
“Now that we’ve refined a way to detect whether or not T cells are reacting to SARS-CoV-2, we believe this information could be used to develop a blood test,” Lineburg said.
“A blood test could help doctors identify patients whose T cells have not started mounting an immune response and who are therefore not fighting the virus and are at higher risk of becoming seriously unwell. Those patients could then be monitored more closely to ensure they receive treatment early, rather than waiting until they experience severe symptoms.
“A blood test that could detect whether a patient is developing an effective immune response would be another important tool in managing how countries deal with the pandemic,” she said.
“These are the first results from this COVID-19 study, and we will follow up with as many participants as possible in [the] future, to improve our understanding of long-term immunity to the virus.”
More than 60 Queenslanders who tested positive for COVID-19 donated blood for the project, and 44 samples were used for the analysis, which included 17 men and 27 women aged between 20 and 75. The remaining samples are still being analyzed.
The researchers received a Medical Research Future Fund grant from the Australian Government to continue their study and explore immunotherapy options for the virus, in collaboration with scientists at The University of Queensland, Monash University and Mater Research.