Detection of toxins-likes peptides in plasma, urine and faecal samples from COVID-19 patients

RATIONALE: SARS-CoV-2 virus that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the SANIST-Cloud Ion Mobility Mass Spectrometry (SANIST-CIMS) technology.

METHODS: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study toxins profiles. SANIST-CIMS instrumental parameters were selected to discriminate the ion cloud containing low and high molecular weight compounds. SANIST-Disc module was employed to investigate the differentially expressed molecules.

RESULTS: Toxin-like peptides, almost identical to toxic components of venoms from animals like conotoxins, phospholipase A2, phospholipase A1, activating prothrombotic factors, phosphodiesterases, zinc metal proteinases, and bradykinins, have been identified. As they were found only in samples from COVID-19 patients, their presence is considered somehow connected to SARS-CoV-2 infection. The presence of these peptides can potentially explain a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like myalgia, headache, encephalopathy, dizziness, dysgeusia, and anosmia. Even if the presence of each individual symptom is not selective of the disease, their combination could be related to COVID-19 in the presence of the panel of detected toxin-like peptides.

CONCLUSIONS: The data reported here suggest an association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.