Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients.
Sasso, Etianne Martini, Muraki, Katsuhiko, Eaton-Fitch, Natalie et al. · Molecular medicine (Cambridge, Mass.) · 2022 · DOI
Quick Summary
This study examined a specific ion channel called TRPM3 in immune cells from patients with ME/CFS and long COVID, comparing them to healthy people. Researchers found that both ME/CFS and long COVID patients had similar problems with how this ion channel functions. The findings suggest that broken ion channels might be part of why these conditions cause long-lasting fatigue and other symptoms.
Why It Matters
This research provides molecular evidence that post-COVID-19 and ME/CFS may share a common biological mechanism involving ion channel dysfunction. Identifying shared pathophysiology could accelerate development of diagnostic tests and targeted treatments for both conditions, and may help clinicians understand why some COVID-19 patients develop long-term illness.
Observed Findings
TRPM3 currents activated by pregnenolone sulfate were significantly reduced in ME/CFS patients compared to healthy controls (p=0.0048)
TRPM3 currents activated by pregnenolone sulfate were significantly reduced in post-COVID-19 patients compared to healthy controls (p=0.0039)
No significant difference was found between ME/CFS and post-COVID-19 patients in TRPM3 current amplitude (p>0.9999)
NK cells from both ME/CFS and post-COVID-19 patients showed resistance to the TRPM3 antagonist ononetin, differing significantly from healthy controls (p<0.0001)
Inferred Conclusions
Post-COVID-19 patients exhibit impaired TRPM3 ion channel function similar to that seen in ME/CFS patients
Impaired TRPM3 channel activity may lead to defective ion mobilization, compromising natural killer cell function and contributing to chronic post-infectious symptoms
ME/CFS and post-COVID-19 condition may share common pathophysiological mechanisms related to ion channel dysfunction
TRPM3 function represents a potential diagnostic marker and therapeutic target for both conditions
Remaining Questions
Does TRPM3 dysfunction occur in other cell types and tissues beyond natural killer cells in these patient populations?
What This Study Does Not Prove
This study does not prove that TRPM3 dysfunction causes ME/CFS or long COVID—it only shows an association in a small sample of patients. The findings are limited to one specific immune cell type (NK cells) and may not reflect what happens throughout the entire body. Furthermore, the study cannot determine whether TRPM3 problems are a primary driver of illness or a secondary consequence of the disease process.
Is TRPM3 dysfunction a cause or consequence of ME/CFS and post-COVID-19, and does restoring TRPM3 function improve symptoms?
What upstream factors trigger TRPM3 dysfunction in these conditions, and how does it relate to the post-infectious trigger in both ME/CFS and post-COVID-19?
Can larger, prospective studies confirm whether TRPM3 dysfunction could serve as a clinically useful biomarker for diagnosis or prognosis?