4.7 Article

Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients

Journal

MOLECULAR MEDICINE
Volume 28, Issue 1, Pages -

Publisher

SPRINGER
DOI: 10.1186/s10020-022-00528-y

Keywords

Post COVID-19 condition; Coronavirus; Myalgic encephalomyelitis; chronic fatigue syndrome; Transient receptor potential melastatin 3; Natural killer cells; Whole-cell patch clamp electrophysiology; SARS-CoV-2

Funding

  1. Stafford Fox Medical Research Foundation [489798]
  2. National Health and Medical Research Council [1199502]
  3. McCusker Charitable Foundation [49979]
  4. Henty Lions Club [4880]
  5. Mason Foundation [47107]
  6. Alison Hunter Memorial Foundation [4570]
  7. Change for ME Charity [4575]
  8. Mr Douglas Stutt, Blake Beckett Trust Foundation [4579]
  9. Ian and Talei Stewart, Buxton Foundation [4676]
  10. Henty Community [4879]

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This study found that patients with post COVID-19 condition may have impaired TRPM3 ion channel function and similarities with ME/CFS.
Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic condition associated with post-infectious onset, impaired natural killer (NK) cell cytotoxicity and impaired ion channel function, namely Transient Receptor Potential Melastatin 3 (TRPM3). Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has resulted in neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations recently recognised as post coronavirus disease 2019 (COVID-19) condition. The symptomatology of ME/CFS overlaps significantly with post COVID-19; therefore, this research aimed to investigate TRPM3 ion channel function in post COVID-19 condition patients. Methods Whole-cell patch-clamp technique was used to measure TRPM3 ion channel activity in isolated NK cells of N = 5 ME/CFS patients, N = 5 post COVID-19 patients, and N = 5 healthy controls (HC). The TRPM3 agonist, pregnenolone sulfate (PregS) was used to activate TRPM3 function, while ononetin was used as a TRPM3 antagonist. Results As reported in previous research, PregS-induced TRPM3 currents were significantly reduced in ME/CFS patients compared with HC (p = 0.0048). PregS-induced TRPM3 amplitude was significantly reduced in post COVID-19 condition compared with HC (p = 0.0039). Importantly, no significant difference was reported in ME/CFS patients compared with post COVID-19 condition as PregS-induced TRPM3 currents of post COVID-19 condition patients were similar of ME/CFS patients currents (p > 0.9999). Isolated NK cells from post COVID-19 condition and ME/CFS patients were resistant to ononetin and differed significantly with HC (p < 0.0001). Conclusion The results of this investigation suggest that post COVID-19 condition patients may have impaired TRPM3 ion channel function and provide further evidence regarding the similarities between post COVID-19 condition and ME/CFS. Impaired TRPM3 channel activity in post COVID-19 condition patients suggest impaired ion mobilisation which may consequently impede cell function resulting in chronic post-infectious symptoms. Further investigation into TRPM3 function may elucidate the pathomechanism, provide a diagnostic and therapeutic target for post COVID-19 condition patients and commonalities with ME/CFS patients.

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