Long Covid Update 2025: Symptoms, Causes, and Latest Clinical Insights

It’s been a while since our last update on Long Covid. Based on the latest research and our own clinical data, this is what we are seeing today. 

Long Covid Update 

The science behind the cause of Long Covid is complex, with current research implicating several mechanisms rather than a single unified cause. The most supported hypotheses include the persistence of viral proteins (including spike protein), chronic neuroinflammation, immune dysregulation, and microvascular disease. Each mechanism may contribute to different symptom clusters, and these pathways are not mutually exclusive. It is important to note that although we have all had Covid, and many of us have received mRNA vaccines without developing prolonged symptoms, the host response must therefore play a significant role. 

Spike Protein Persistence in Long Covid 

Some studies suggest that the persistence of Covid viral fragments—especially spike protein or nucleoprotein—in tissues may act as a chronic antigenic stimulus, prolonging immune system activation long after the acute infection has resolved. This ongoing immune response may drive persistent symptoms. In my patients, most present with high levels of Spike IgG, which may be due to ongoing spike protein production. 

The recent Attomarker test can identify different subtypes of Spike IgG (Delta, Omicron, etc.), which may enable more targeted treatments depending on the subtype and quality of Spike IgG. Attomarker is also developing a blood test capable of detecting spike protein. 

Neuroinflammation in Long Covid 

Chronic neuroinflammation is strongly associated with “neuro-Long Covid.” Evidence indicates persistent activation of glial cells, dysregulated cytokine profiles, and disrupted neurotransmitter signalling that affects cognition, mood, and fatigue. This mechanism may arise from immune activation, viral protein persistence, or microvascular impairment leading to blood–brain barrier disruption. This forms the basis of our treatment using anti-inflammatories such as low-dose naltrexone and baricitinib. A natural treatment approach is the McCullough protocol, which combines curcumin with nattokinase and bromelain. 

Microvascular Disease and Long Covid Symptoms 

Microvascular dysfunction and endothelial injury are also implicated. SARS-CoV-2 can infect endothelial cells, causing small-vessel inflammation, microthrombi, and long-term impairment of blood flow. This process is believed to contribute to the neurological, cardiopulmonary, and systemic symptoms seen in Long Covid patients. In Hong Kong, we are fortunate to have easy access to venous blood gas testing. Patients with this issue often present with low venous oxygen levels, making this a useful biomarker. Treatments include natural agents such as nattokinase, as well as blood-thinning medications. 

Immune Dysregulation in Long Covid 

There is evidence of long-lasting immune abnormalities, including persistent pro-inflammatory cytokines, autoantibody production, and irregular T-cell profiles, all of which may sustain chronic symptoms and multi-organ involvement. 

Long Covid: Current Understanding and Outlook 

Current scientific consensus suggests that Long Covid is a multi-system condition, likely resulting from an interplay of spike protein persistence, chronic inflammation (including neurological inflammation), and microvascular pathology. No single pathway explains all cases, and overlapping mechanisms are probable in individual patients. This growing understanding is helping us improve treatment for those living with this chronic and disabling condition.

To learn more, visit our Long Covid Resource Centre.

References

1. Pathophysiology and mechanism of long COVID: a comprehensive review https://pmc.ncbi.nlm.nih.gov/articles/PMC9132392/ 
2. Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives https://pmc.ncbi.nlm.nih.gov/articles/PMC11429791/
   
3. Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review https://pmc.ncbi.nlm.nih.gov/articles/PMC11050596/  
4. Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms https://pmc.ncbi.nlm.nih.gov/articles/PMC10545886/  
5. The Omics Landscape of Long COVID—A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery https://pmc.ncbi.nlm.nih.gov/articles/PMC11969314/   
6. Long Covid: Untangling the Complex Syndrome and the Search for Therapeutics https://pmc.ncbi.nlm.nih.gov/articles/PMC9864843/  
7. Long COVID: mechanisms, risk factors and recovery https://pmc.ncbi.nlm.nih.gov/articles/PMC10103775/
8. Attomarker.com