Australian scientists have discovered blood signatures in patients with COVID-19 similar to those found in individuals suffering from diabetes and cardiovascular disease in research which could not only assist with COVID-19 testing but also help with monitoring for long-term health effects.

The study1, which was published earlier this month, compared the blood plasma of individuals infected with COVID-19 with those who had tested negative to the virus and found that COVID positive patients exhibited different diagnostic markers that remained after they had recovered and could demonstrate the long-term effects of the disease.

Professor Jeremy Nicholson, lead author of the paper and director of Murdoch University’s Australian National Phenome Centre, said the discovery had created a new type of test for COVID-19.

“This work opens the door to a new type of test that does not depend on detection of the virus itself but that can help discriminate COVID-19 infections, especially when used in conjunction with conventional PCR testing,” he said.

Polymerise chain reaction (PCR) testing directly detects the RNA of the virus through swabbing a person’s nose and throat. In contrast, the new test looks for markers in an individual’s blood and could be used to increase the security of existing testing procedures such as those used in quarantine, Professor Nicholson said.

The test could be key to future easing of state and national lockdowns especially as the highly infectious UK COVID-19 variant spreads around the world.

“We really do not want the new variant to escape into the general population of WA or anywhere else,” he said.

“The new variant poses a much more significant infectious threat than the previous versions of the virus and although it is not significantly more virulent it is much easier to catch and that includes children.”

COVID-19 signatures using magnetic fields

In creating the new test, Professor Nicholson and his team used nuclear magnetic resonance, an analytical chemistry technique that can accurately identify what a substance is made of. In essence, NMR uses magnetic fields to determine the structure of molecules within a material such as plasma.

The researchers looked for a range of plasma lipoproteins — which are involved in the transport of materials like fat and cholesterol — as well as smaller molecules such as amino acids and glucose. Cytokines and chemokines, molecules involved in the pro and anti-inflammatory processes, were also searched for.

“COVID-19 affects multiple organ systems including cardiovascular, liver and gut, and the molecules we are measuring are altered in these pathologies,” Professor Nicholson told Lab Down Under.

Plasma was collected from 15 patients who had tested positive for COVID-19, 34 individuals who were healthy, and 35 people who had COVID-19 or influenza-type symptoms but who also tested negative.

Despite the small sample sizes, Professor Nicholson was confident in the results.

“Firstly, the models are exceptionally strong. The biochemical signature of COVID-19 is multi-system and strongly expressed. Second, we have multiple time points from a number of patients and these show an integrated through time story.

“Thirdly, we have the benefit of studying a Cambridge University and several other major cohorts which are much larger — several hundred samples through time which strongly supports these observations and of course allows us to go further. We are writing these papers up now.”

Recovered but not back to normal

The signatures from patients’ plasma remained abnormal even though the respiratory symptoms caused by COVID-19 had lessened and the individuals were found to be virus-free, Professor Nicholson said.

“This raises the possibility that some patients may not fully recover from the systemic effects of the infection and are left with other metabolic disorders that change their long-term disease risks and this is a possible concern for so-called recovered patients.”

The patterns of plasma lipoproteins in the blood of COVID-19 patients changed dramatically, becoming closer to those found in individuals with diabetes, atherosclerosis and cardiovascular disease, the researchers found.

“There were strong indications of the underlying systemic disease in the NMR data indicative of diabetes, liver dysfunction, and cardiovascular abnormalities,” they wrote in the paper.

“Long-term cardiovascular problems appear to be common for COVID-19 patients, and these may be reflected in abnormal lipoproteins after the acute respiratory symptoms have subsided, indicating a potential role for these measurements in the assessment of systemic patient recovery.”

One unknown was how reversible these changes were over time, Professor Nicholson said, noting that his team was working on examining this area at the moment.

“These metabolic changes were closely linked to the immunological parameters that drive or are associated with the lung pathology and indeed are involved in the most severe forms of the disease,” he said.

“This is consistent with our earlier findings showing that COVID-19 is a systemic disease with multi-organ effects, that can occur in addition to the better-known lung pathology.”

Refining the test for the real world

The findings outlined the importance of following up with “recovered” COVID-19 patients over the long-term, assessing health status, and trying to mitigate any long-term health effects, Professor Nicholson said.

The team was already working on more papers to refine the test, he told Lab Down Under. The next step is to get regulatory approval before it was ready to deploy in a real world setting.

“Our main application in WA would be to provide orthogonal testing capability to the widely used but imperfect PCR. This is basically to improve the safety of the biosecurity systems to minimise the chance of infected patients getting through quarantine.

“The methods can also be used to assess long-term recovery from the disease which is slow and many people, possibly 50 per cent, have problems for at least six months.”

Blood plasma was collected from patients in the Fiona Stanley and Royal Perth Hospitals. The samples were analysed using NMR machines at ANPC, which will continue this research into the long-term effects of COVID-19.

“We are now studying follow up samples from WA and UK and developing new methods to assess functional recovery and where necessary to identify patients who need further treatments to mitigate long term effects,” Professor Nicholson told Lab Down Under.

The research was funded by Spinnaker Health Research Foundation, the McCusker Charitable Foundation, and the WA Government.

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1 Lodge S, Nitschke S, Kimhofer T, Coudert J, Begum S, Bong S, Richards T, Edgar D, Raby E, Spraul M, Schaefer H, Lindon J, Leng Loo R, Holmes E, Nicholson J. NMR Spectroscopic Windows on the Systemic Effects of SARS-CoV-2 Infection on Plasma Lipoproteins and Metabolites in Relation to Circulating Cytokines. Journal of Proteome Research, January 11, 2021.

Featured image: COVID-19 test. Picture by fernando zhiminaicela from Pixabay. Used under the Pixabay Licence.

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