“Long-Spike” Theory Links Persistent Antigenemia from COVID-19 Infections to Long COVID
Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 18, 2026 39 minutes ago
Scientists are investigating whether SARS-CoV-2 proteins that remain in the body long after an acute infection could help explain why some people develop persistent, multisystem symptoms known as Long COVID.
Persistent SARS-CoV-2 antigens detected months after infection are being investigated as one possible
contributor to Long COVID
The review was conducted by Elifcan Aladag and Ibrahim Celalettin Haznedaroglu of the Hematology Department, Faculty of Medicine, Hacettepe University, Ankara, Turkey, and Ugur Nadir Karakulak of the Cardiology Department, Faculty of Medicine, Hacettepe University.
Why persistent spike protein matters
The SARS-CoV-2 spike protein is best known for allowing the virus to enter human cells by interacting with the ACE2 receptor. However, experimental research indicates that spike may also influence endothelial cells lining blood vessels and activate inflammatory and coagulation-related pathways.
Studies have shown that spike exposure can increase vascular permeability and promote inflammatory signaling. Researchers have also linked spike-related signaling experimentally to endothelial activation, complement activity and platelet responses, potentially contributing to the interconnected processes involved in microvascular injury and immunothrombosis.
Importantly, the authors caution that some laboratory experiments used spike concentrations substantially higher than levels detected in human circulation. This means such experiments demonstrate biological plausibility but cannot establish that the much lower concentrations measured in patients directly cause vascular damage.
Viral antigens detected more than a year later
One of the most intriguing findings highlighted in this
Thailand Medical News report concerns evidence of persistent SARS-CoV-2 antigens after infection.
Using highly sensitive testing, researchers in an earlier study detected circulating full-length spike protein in a subset of people with post-acute COVID-19 symptoms, sometimes more than 12 months after their original infection.
Another investigation detected one or more SARS-CoV-2 antigens in approximately one-quarter of participants at one or more testing points extending as far as 14 months after infection.
Researchers have additionally found persistent viral material in tissues outside the lungs, strengthening the possibility that tissue reservoirs could provide a continuing source of viral antigens in some people.
Could persistent antigens sustain Long COVID?
The researchers propose a conceptual framework they call the “Long-Spike” hypothesis. Under this theory, persistent or dysregulated spike-related antigen exposure could potentially sustain endothelial activation, immune dysregulation, platelet hyperreactivity, complement activation and microvascular dysfunction.
Together, these interconnected abnormalities could potentially contribute to cardiovascular, hematological, neur
ological and autonomic manifestations associated with Long COVID. The review’s diagram on page 8 illustrates this proposed network, connecting persistent spike exposure with vascular injury, immune abnormalities, microvascular thrombosis and organ-specific effects.
However, there is an important limitation: persistent antigenemia is not detected in every person with Long COVID. Simply finding viral antigens also does not demonstrate that they are biologically active or responsible for an individual’s symptoms.
Conclusions
The “Long-Spike” hypothesis offers a potentially important explanation for how persistent SARS-CoV-2 antigens could contribute to chronic symptoms in a subset of people after infection. However, researchers emphasize that the theory remains unproven and Long COVID likely involves several overlapping mechanisms. Prospective studies linking antigen levels, tissue reservoirs, immune abnormalities and specific clinical symptoms over time will be essential for determining whether persistent antigenemia is a cause, contributor or simply a marker of underlying disease processes.
The study findings were published in the peer reviewed journal: Biomedicines.
https://www.mdpi.com/2227-9059/14/9/2090
Read Also:
https://www.thailandmedical.news/articles/long-covid 
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