Identifying Long COVID Biomarkers

For millions of people suffering from the lingering effects of a SARS-CoV-2 infection, the lack of a definitive diagnostic test has been a major hurdle. Doctors currently rely on a process of exclusion to diagnose Long COVID, which often leaves patients feeling unheard or invalidated. However, recent breakthroughs in blood protein analysis are changing this narrative. New studies suggest that specific biomarkers in the blood can distinguish Long COVID patients from those who have fully recovered, paving the way for the first objective diagnostic tool.

The Breakthrough in Blood Protein Analysis

The most significant recent advancement comes from a study published in the journal Science by researchers at the University of Zurich. The team, led by immunologist Onur Boyman, identified a specific “signature” in the blood serum of patients with active Long COVID symptoms.

This research focused on the complement system. This is a part of your immune system that typically helps fight off infections and then goes dormant once the threat is gone. In patients with Long COVID, the study found that this system remains in a state of high alert long after the initial virus has cleared.

Key Findings from the Zurich Study

  • The Cohort: The researchers analyzed blood samples from 113 COVID-19 patients and followed them for up to one year. They compared these against 39 healthy control subjects.
  • The Biomarkers: They identified distinct changes in blood serum proteins. Specifically, they noticed an imbalance in proteins related to the complement system. This dysregulation causes tissue damage and inflammation.
  • Accuracy: The protein signature allowed the researchers to distinguish patients with Long COVID from those who recovered with a high degree of accuracy.

Why the Complement System Matters

To understand why this test is effective, you must understand what the complement system does. It is part of the innate immune system. When a virus enters the body, the complement system activates proteins that punch holes in the pathogen or tag it for destruction by other immune cells.

In healthy recoveries, this system resets. In Long COVID cases, the study suggests that “active Long COVID” is essentially an autoimmune-like state where the body continues to attack itself via these blood proteins.

This creates a tangible, physical trail of evidence. It moves the diagnosis away from subjective symptom reporting (like fatigue or brain fog) and toward hard biological data.

Other Promising Biomarker Candidates

While the complement system is a leading candidate, other institutions are finding different pieces of the puzzle. The complexity of Long COVID means there may be multiple “subtypes” of the condition, each requiring different tests.

Researchers at Yale, led by Akiko Iwasaki, conducted a study focusing on hormonal imbalances. Their research indicated that patients with Long COVID had cortisol levels roughly half those of healthy individuals. Cortisol is the body’s primary stress hormone and plays a vital role in regulating inflammation and energy. A simple blood panel checking for significantly depressed cortisol levels could serve as another diagnostic layer.

Mount Sinai: T-Cell Exhaustion

Another avenue of research involves T-cells. Studies out of Mount Sinai have observed “exhausted” T-cells in patients months after infection. These immune cells appear worn out and function poorly, which correlates with the persistent fatigue reported by patients.

The Path to a Commercial Test

Identifying these biomarkers in a research lab is step one. Getting a standardized test into a clinic is step two. Currently, there is no FDA-approved blood test for Long COVID available at commercial labs like Quest Diagnostics or Labcorp. However, the identification of these protein signatures accelerates the timeline for development.

Steps Remaining Before Public Availability

  1. Validation: Larger clinical trials are needed to verify these findings across diverse populations. The initial studies often have small sample sizes (under 300 people).
  2. Standardization: Labs must agree on exactly which proteins to measure and what the “cutoff” levels are for a positive diagnosis.
  3. Machine Learning Integration: Because the blood signature involves ratios of multiple proteins rather than just one “positive/negative” marker, AI and machine learning models are being developed to interpret the blood panels quickly.

Impact on Treatment and Insurance

The arrival of a blood test will do more than just provide a name for the illness. It will fundamentally change the financial and medical support available to patients.

Currently, many insurance providers deny disability claims for Long COVID due to a lack of “objective medical evidence.” A validated blood protein test would provide the concrete proof required for short-term and long-term disability claims. Furthermore, if doctors know specifically that the complement system is overactive, they can prescribe existing drugs that target that specific pathway, rather than just treating general symptoms.

Frequently Asked Questions

Is there a blood test for Long COVID available right now? No, there is currently no commercially available blood test approved by the FDA for diagnosing Long COVID. The tests described above are still in the research and validation phases.

What is the main biomarker researchers have found? The most prominent recent finding involves proteins associated with the complement system, a part of the immune system that causes inflammation. Other studies point to low cortisol levels and Epstein-Barr virus reactivation markers.

When will a test be available to the public? While exact dates are difficult to predict, the rapid pace of publication in major journals like Science and Nature suggests that diagnostic tools could enter clinical trials or limited commercial use within the next 12 to 24 months.

Can standard blood tests detect Long COVID? Generally, no. Standard blood panels (CBC, metabolic panels) usually come back normal for Long COVID patients. This is why specialized testing for specific protein signatures is required.

Who is leading this research? Major contributions are coming from the University of Zurich (Onur Boyman), Yale School of Medicine (Akiko Iwasaki), and the Icahn School of Medicine at Mount Sinai.