Study links blood protein changes to long COVID

Jolyon Attwooll

22/01/2024 4:47:47 PM

Researchers are hopeful that the findings could help improve diagnosis and treatment of a condition it says remains ‘poorly understood’.

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The causes of long COVID remain poorly understood, according to the study authors.

Researchers who tracked blood serum changes in long COVID patients believe their findings could reveal biomarkers that eventually improve diagnosis and treatment of the condition.
Authors of the study, Persistent complement dysregulation with signs of thromboinflammation in active long COVID, noted that causes behind the condition remain ‘poorly understood’.
Published in the journal Science, their research details findings from tracking the blood serum samples of 113 patients with confirmed acute COVID-19, alongside those of 39 healthy control patients.
With follow-ups at six months and 12 months, 48 of the COVID-19 patients were confirmed with long COVID. However, eight reported only changes in smell or taste, and were excluded from the final study.
The samples from the remaining 40 patients were used to look into the mechanisms underlying long COVID, according to the study authors.
‘Patients experiencing long COVID exhibited changes to blood serum proteins, indicating dysregulated activation of the complement system, altered coagulation, and tissue injury, suggesting ongoing thromboinflammatory responses,’ they wrote.
The complement system is described by the journal as ‘part of the innate immune system [which] contributes to immunity and homeostasis by targeting pathogens and damaged cells, among other functions’.
‘These findings provide a resource of potential biomarkers for diagnosis and may inform directions for treatments,’ the authors conclude.
David Lynn, a professor of systems immunology at Flinders University, said the Swiss-funded study used advanced methods and has some notable findings.
‘These analyses indicate that a key component of our innate immune system, called the complement system, is dysregulated in individuals with long COVID,’ he said.
‘Importantly, this finding was replicated in an independent cohort in the USA.’
However, he suggests more research is needed to fully understand the causes of long COVID, and develop treatments.
‘While these findings are exciting and important, it is important to note that this publication is one of several high-profile publications published in the last year or two showing that different aspects of the immune system are dysregulated in long COVID,’ he said.
‘Much work remains to be done to unify the different mechanisms that have been proposed in these different studies and more importantly to develop novel treatments based on these findings for patients suffering from this debilitating chronic condition.’
Professor Jeremy Nicholson, the director at the Murdoch University’s Australian National Phenome Centre, agrees that further research is required.
‘This paper gives new insights into the complement protein perturbations but still does not explain the diversity of the long COVID symptoms or their differential expression between individuals,’ he said.

‘In fact, the work revolves around proteomic data on a relatively small number of patients so in itself is unlikely to explain everything.
‘There are also other factors [also poorly understood] in long COVID – like the disruption of the microbiome relating to gastrointestinal effects – which are also likely to influence immune regulation and control in their own right.’

He said more comprehensive studies will be needed using greater numbers of people.
‘Sadly, there is no shortage of long COVID patients to study,’ Professor Nicholson noted.
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