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May 29, 2024

New research brings hope for understanding and treating long COVID

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Jan 23, 2024

Long COVID, where COVID-19 symptoms persist for months or years after the initial infection, has remained a complex and mysterious illness. But two new studies published this week are providing clues into its mechanisms and potential treatments.

Blood protein signatures point to immune system involvement

Researchers from the University of Zurich have identified signature changes in blood proteins of long COVID patients, indicating immune system activation may be driving ongoing symptoms [1]. The findings point to a state of chronic inflammation and ongoing cellular damage.

Over 5000 proteins were analyzed using mass spectrometry blood tests from over 200 patients with long COVID and healthy controls. The team discovered a distinct inflammatory signature dominated by signs of complement system activation. The complement system is part of the innate immune response and drives elimination of pathogens, but unchecked activation can damage host tissues.

“It looks like in some people with long COVID, the complement system remains activated, potentially inflicting damage that reaches many organ systems,” explained study leader Onur Boyman.

Patients with long COVID symptoms Healthy controls
↑ complement proteins Normal levels
↑ inflammatory signals
Signs of cellular damage

This analysis also revealed markers of neurological tissue injury, fatigue, and post-exertional malaise – all hallmark symptoms of long COVID.

“The findings indicate that long COVID is caused by an overactive immune response that fails to shut off after the initial infection is over,” summarized Eric Topol, Scripps Research professor of molecular medicine [2].

New biomarker to identify long COVID patients

Not only do these findings provide clues to disease mechanisms in long COVID, researchers suggest this protein signature could serve as a much-needed biomarker to identify patients. Difficulty diagnosing this collection of nebulous symptoms has posed a major barrier to researching and treating what’s estimated to impact up to 30% of COVID-19 survivors [3].

“A proteomic signature may not only help diagnose long COVID but also discriminate it from ME/CFS,” said Boyman, referring to myalgic encephalomyelitis/chronic fatigue syndrome with significant symptom overlap. His team is now working to validate their results in additional patients and streamline testing methods to be amenable to widespread clinical use.

Commercial labs are also jumping on board these findings – SomaLogic just announced development of a diagnostic test based on the Zurich group’s results, slated to launch later this year [4].

Targeting the complement system as treatment

In addition to diagnostic potential, these molecular insights may uncover therapeutic inroads for this disabling condition estimated to have affected over 100 million people worldwide [5].

“Targeting the complement system could be a promising strategy,” explained Boyman. His group found a subset of patients with autoantibodies blocking complement regulation, leading to excess activity. Specialized therapies modulating overactive complement pathways already exist for other diseases and could be repurposed. More research is underway.

An accompanying commentary written by immunologists John Ioannidis of Stanford and Reto Auer of the University of Zurich praised these important steps towards solving long COVID while also citing limitations in the study’s design [6].

“We have to make sure cause and effect are really connected here,” said Ioannidis. “Does complement activation actually happen before long COVID symptoms arise or vice versa?” The correlational data leaves questions around directionality. Randomized interventional trials targeting the complement system will be important next steps.

Post-vaccination lower incidence of long COVID offers more clues

In aligned news this week, a large observational study from Washington University researchers found people vaccinated prior to contracting COVID-19 had a 15-25% lower risk of developing long COVID compared to the unvaccinated [7]. Analyzing private insurance records of nearly 2 million Americans, this study accounted for over 3,000 potential confounding variables.

“Post-vaccination long COVID is more rare, symptom burden is reduced, and disability time is shortened,” explained senior author Ziyad Al-Aly, Washington University clinician and epidemiologist.

The researchers hypothesize vaccines dampen uncontrolled immune reactions to the SARS-CoV-2 virus, reducing risk of persistent collateral inflammation. This supports models from the Zurich group citing overexuberant complement activity and lack of immune regulation. Al-Aly suggests these mechanistic insights could inform development of therapeutics and vaccines specifically targeting long COVID. Clinical trials testing this hypothesis have recently been approved [8].

Lingering questions and need for awareness

While these studies provide early clues, glaring questions remain around the range of biological pathways active in long COVID as well as the disease’s scope and trajectory at a population level [9]. Symptoms are diverse, severity varies greatly between patients, and kids aren’t spared either.

Public health experts cite urgent need to direct attention and resources towards understanding long COVID in order to stem the incoming wave of disability already estimated to eclipse that caused by cancer, heart disease and diabetes combined [10].

While this week’s findings provide initial steps, London School of Hygiene and Tropical Medicine professor Peter Openshaw issued sober advice: “We are still a long way from having diagnostic tests or treatments for long COVID.” [11]

In summary, groundbreaking studies this week provide early evidence validating sufferers’ experience and bringing hope that science and medicine may find ways to diagnose and treat this crushing illness. But there is still a long road ahead.

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AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.

By AiBot

AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

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