A team of international researchers has developed a comprehensive computer model capable of predicting an individual’s capacity to recover from COVID.
The study, published 31 January 2023 in Nature Immunology, revealed distinct ‘systemic recovery’ profiles, with specific progression and recovery of the inflammatory, immune cell, metabolic and clinical responses to COVID.
Their data suggested that a limited number of pathophysiologic processes impacted many of the parameters which emerged together during the early phase of infection with SARS-CoV-2 and were the best predictive indicator of a poor recovery.
The findings were the result of a three-year partnership between Dr Hélène Ruffieux and Professor Christoph Hess from the University of Cambridge University, the Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR), the BioResource COVID Collaboration, and the Australian National Phenome Centre (ANPC) research facility at Murdoch University.
The team followed the course of the disease in 215 patients for up to a year after infection with the original Wuhan strain, measuring a range of immune system cells and metabolic parameters in blood plasma to estimate the probabilities of unvaccinated patients making a full recovery from the disease.
Professor Jeremy Nicholson, Pro-Vice Chancellor for Health Sciences and Director of the ANPC, said the research exemplifies the type of breakthroughs possible when powerful technologies and effective clinical collaboration come together.
“We have taken advantage of very well collected and curated patient blood samples from Cambridge University’s Addenbrookes Hospital and combined our state-of-the-art technology at the ANPC to produce a uniquely detailed individual mapping of the disease progression and outcomes,” Professor Nicholson said.
“The research highlights multiple new features of the disease, which is highly variable in terms of severity and persistence: importantly, the interplay between the immune system and the blood metabolic profiles gives deep insights into how individuals vary and how that variation impacts on long-term outcomes, including long-COVID or even death.”
His colleague and Deputy Director of the ANPC, Professor Julien Wist, explained that the model emphasised the importance of the frequency of different types of immune cells and how specific amino acid and lipoprotein pathways are disturbed because of the inflammatory effects of COVID.
“NK cells play a central role in antiviral immunity through the secretion of pro-inflammatory cytokines and cytotoxic activity and had the largest weight in the first predictive signature, with low absolute counts associated with poor outcomes,” Professor Wist said.
“This reduction of NK cells in peripheral blood from individuals with unresolving CRP suggests an inflammation-driven perturbation of the NK cell compartment, however the precise contribution of NK cell function to SARS-CoV-2-related acute and post-acute pathology remains unresolved.
“Pro-inflammatory cytokines activate the kynurenine pathway through induction of indoleamine 2,3-dioxygenase (IDO-1), and it is plausible that abnormal levels of kynurenine-pathway intermediates, coupled with a significant reduction of serotonin abundance, contribute to the neurological sequelae (for example, fatigue, weakness, chronic pain) of long-COVID, whereas pathologic smell and taste may be related to more direct nerve sheath damage.”
“What is worrying, is that the long-term disease trajectory appears to be set very early during infection, which means that for unvaccinated patients, urgent action would be needed to mitigate the long-term negative consequences of the disease,” Professor Nicholson added.
“Our next task is to operationalise this model by reducing it down to the most critical parameters and ones that can be measured rapidly ideally using only one analytical tool, and that is what we are working on now.”
WA’s Chief Scientist, Professor Peter Klinken, said that through such international collaborations the ANPC and WA science continued to have an impact on the world stage in critical areas of unmet medical need.
“COVID remains a global problem and here the ANPC, a WA-based national science facility working with Cambridge, has made a major contribution to understanding the complex disease process that will have new clinical translational impacts for real people,” he said.
“COVID is not the last emergent disease threat that we will face, and we are fortunate to have a defensive weapon in the form of the ANPC research facility at Murdoch University.”
The research is currently being augmented and validated by thousands of blood plasma samples collected by Harvard University, who are also working closely with ANPC to predict long-COVID outcomes.
“We have published the data and the mathematical model developed with Cambridge – currently for research use only – and it is available online to anyone who wants to examine how the different parameters interact,” Professor Wist said.
“Our study does not reflect the current epidemiological situation, which is a limitation, but importantly however, our statistical framework is transferable to new cohorts (vaccinated, treated), facilitating systematic comparative work.”
Those interested can find out more by following the link below:
http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app/