A recent multicenter study from the University of Zurich is causing a stir in the media. The researchers have found possible blood biomarkers for diagnosing Long COVID. In this blogpost, Altea gives a summary of the findings. More Updates on the implications of this study will follow.
The researchers followed 113 COVID-19 patients for up to 1 year. Participants were confirmed to have acute SARS-CoV-2 infection through PCR tests and were assessed at 6- and 12-months post-infection. Additionally, 39 healthy adults served as controls. The patients were categorized into different groups based on the severity and duration of their symptoms.
1. Patient Groups:
- 33% of COVID-19 patients had a severe disease course.
- 58% fully recovered, while 42% reported persistent symptoms at 6 months (referred to as 6-month Long COVID).
- Serum samples from 40 patients with 6-month Long COVID were used for further investigation.
2. Serum Proteome Analysis:
Serum proteins in patients’ blood were assessed during acute COVID-19 and at 6-month follow-up.
- Differences in serum protein levels were observed between severe and mild COVID-19 cases and between patients with or without 6-month Long COVID.
- Enriched biological pathways related to complement cascade and immune system were identified.
3. Complement System Dysregulation:
The complement system is a part of the human immune system. It consists of a group of proteins that work together to defend the body against infections, particularly by enhancing the immune response.
The proteins in the complement system are designated by numbers and letters. Some of the key components include the complement proteins: C1 to C9. The proteins in the complement system work together in forming complexes that can attack and eliminate pathogens. In healthy individuals, the complement system is highly regulated to prevent unnecessary activation and damage to the body's own cells.
- The study noted dysregulation of the complement system in 6-month Long COVID patients, particularly affecting the complement protein 7 (C7).
- C7 complexes were consistently reduced in active Long COVID at 6-month follow-up but normalized upon recovery.
4. Thromboinflammatory Responses:
Thromboinflammatory molecules play a role in both inflammation and blood clotting (coagulation). The interplay between inflammation and coagulation is complex and involves various factors. Thromboinflammation is often associated with pathological conditions where there is an abnormal activation of both the immune and coagulation systems.
- Long COVID patients exhibited signs of thromboinflammatory responses, including increased levels of the factor vWF (von Willebrand factor), coagulation factors, and platelet-activating factor acetylhydrolase.
- Elevated monocyte–platelet aggregates were found in Long COVID patients, particularly those progressing to 12-month Long COVID.
5. Antibody Associations:
The study also assessed autoantibodies and antiviral antibodies.
- Long COVID patients had increased antinuclear antibodies (ANA) and alterations in anti-chemokine antibodies.
- IgG (antibodies produced by plasma cells in the blood) titers against herpesviruses were proportionally increased in Long COVID patients, with specific associations observed for enterovirus B and human herpesvirus 5 (CMV).
- No overall difference in CMV or Epstein-Barr virus (EBV) infection prevalence was found between patients with and without 6-month Long COVID.
Overall, the study identified dysregulation in the complement system, thromboinflammatory responses, and specific antibody associations in Long COVID patients, providing insights into potential mechanisms underlying persistent symptoms. The findings suggest that especially complement and thromboinflammatory proteins could serve as biomarkers for Long COVID diagnoses.
