A major new study published this week has uncovered important new evidence about what causes lingering symptoms in people with long COVID. Researchers analyzed blood samples from over 200 patients and identified signature changes in levels of proteins related to activation of the immune system.
Blood protein changes point to immune system involvement
The study, published in the journal Science on January 18th, was led by scientists at University Hospital Zurich in Switzerland. They compared blood samples from patients reporting long COVID symptoms to healthy controls and COVID-recovered patients without long term issues.
Using advanced proteomic profiling techniques, they identified a distinct signature of proteins in long COVID patients indicating prolonged activation of immune pathways, especially the complement system involved in inflammation. As senior author Onur Boyman put it:
“We found abnormal levels of some plasma proteins in people with long COVID. These proteins are linked to viral recognition, inflammation, activation of complement, and cellular stress.”
Table 1: Key findings of long COVID blood protein study
| Finding | Details |
|---|---|
| Immune activation | Increased levels of proteins for recognizing viruses, inflammation signaling, immune cell recruitment |
| Complement involvement | Overactivity of complement system which tags cells for removal |
| Cell damage | Presence of intracellular proteins in blood indicating cell breakdown |
The researchers concluded that inappropriate ongoing immune activation, rather than the virus persisting, seems the most likely cause of long COVID issues. Treatments targeting the complement pathway may be beneficial.
Potential for diagnostics and better treatment
This large proteomic analysis provides confirmation that long COVID represents a form of post-viral autoimmunity. While the immune system plays an important role in initially fighting off COVID-19, in some people it fails to properly switch off, leading to systemic inflammation and symptoms that won’t resolve.
As Dr. Topol commented on Twitter, this is “The first substantial biological explanation for #LongCovid –persistent complement activation driving symptomatology”. Finding a distinct molecular signature is also an important step towards diagnostic tests and targeted immunomodulatory therapies.
Dr. Angela Maas, who heads the Dutch long COVID observational study, highlighted the potential for “Better recognition of patients & development of therapy”.
Ongoing research efforts
In conjunction with the blood protein study, researchers from Australia also published multi-omics data on Thursday identifying potential tissue-specific biomarkers for diagnosing long COVID.
Several research groups presented further findings at a Long Covid summit held at Imperial College London on Friday January 20th. Dr. Olli Polo from Helsinki University Hospital showcased results demonstrating neurological impacts like brain fog, headache and fatigue. Meanwhile Dr. Isabelle Vonderheyden of University Hospital Aachen discussed cardiovascular issues that develop in up to 25% of long COVID patients.
Calls for more support
Long COVID continues to disable nearly 150 million people worldwide who had COVID-19. At a congressional hearing on Tuesday January 17th, representatives from several US long COVID advocacy groups called for expanded medical leave protections and disability benefits.
As Rep. Ayanna Pressley affirmed in a tweet, long COVID “disproportionately impacts the disabled, women & BIPOC. We must center equity in our policymaking.” Ongoing research to understand long COVID biology and development of diagnostics remain crucial to provide patients struggling with these lingering symptoms the care and support they need.
What’s next?
While much progress has been made, there is still significant work ahead to translate these research findings into tangible improvements for long COVID patients. Larger longitudinal studies following patients over time are underway and will provide more definitive data.
Researchers also caution that the heterogeneity of long COVID symptoms means there could be multiple mechanisms driving different manifestations of the condition. As Dr. Amy Proal, an expert in post-infectious disease, told Bloomberg:
“This study provides evidence that there’s an association between long Covid and activation of the complement system. But long Covid itself is multifactorial — many things can cause similar symptom clusters.”
Continuing global, collaborative efforts between clinicians, researchers, and advocates is key to unraveling the mysteries of long COVID. This week’s developments represent important steps on that path to better diagnosing, managing and one day curing this complex medical condition impacting millions worldwide.
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