Toxin-like peptides in plasma,urineand faecalsamples from COVID-19 patients.

Abstract

Background:SARS-CoV-2 thatcausesCOVID-19 diseaseand led to the pandemic currently affecting the worldhas beenbroadlyinvestigated. Different studies have been performed tounderstandthe infection mechanism,andthe involved human genes, transcripts and proteins.In parallel, numerous clinicalextra-pulmonarymanifestations co-occurringwith 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 theLiquidChromatographySurface-ActivatedChemicalIonization- Cloud IonMobilityMassSpectrometry. Methods:Plasma,urineand faecalsamplesfrom COVID-19patients and controlindividualswereanalysedtostudypeptidomictoxins'profiles.Protein precipitation preparation procedure was usedfor plasma,toremovehigh molecular weight proteinsand efficiently solubilize the peptide fraction;in the case of faeces and urine,direct peptide solubilization was employed. Results:Toxin-likepeptides,almost identical to toxic components of venoms from animals,likeconotoxins, phospholipases,phosphodiesterases, zinc metal proteinases, and bradykinins,wereidentifiedin samples from COVID-19 patients, but not in control samples. Conclusions:Thepresenceof toxin-like peptidescouldpotentiallybeconnected to SARS-CoV-2 infection.Theirpresencesuggestsapossibleassociation between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals.Their involvement ina large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, likeneurologicalones, cannot be excluded. Althoughthe presence of each individual symptom is not selective of the disease, their combinationmightbe related to COVID-19bythecoexistenceofthe panel of the heredetectedtoxin-like peptides.The presence of these peptides opens new scenarios on theaetiologyof the COVID-19 clinical symptoms observed up to now, including neurological manifestations.