Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients

Abstract

Background: SARS-CoV-2 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 Liquid Chromatography Surface-Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry. Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins’ profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed. Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples. Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.

Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?

“…They observed that bacterial endotoxins induced a lower rate or even inhibited viral replication [ 35 ]. Similar to our studies [ 6 , 7 ], we highlighted several toxin-like proteins in the plasma, feces, and urine of COVID-19 patients, which were produced by bacteria as a consequence of interaction with SARS-CoV-2. We have shown that these oligopeptides are derived from bacterial cultures [ 6 , 7 ] and we are testing them in mice (data in preparation).…”

“…To deepen our previous studies [ 6 , 7 ], analyses using immunofluorescence, TEM, and immunogold marking techniques were conducted. These analyses showed infection of bacteria by the SARS-CoV-2 virus after 30 days of bacterial culture, where mammalian eukaryotic cells are excluded, in agreement with current literature that excludes their survival beyond 48 h [ 20 ].…”

“…[ 5 ]. Our previous work showed that people with COVID-19 had toxin-like peptides, which were almost identical to the toxic components of animal venoms, such as conotox, phospholipases A2, phosphodiesterases, zinc metal proteinases, and bradykinins, in both blood, feces, and urine [ 6 ]. In a later study, we observed spontaneous replication of SARS-CoV-2 in bacterial cultures from patient feces for up to 30 days and beyond [ 7 , 8 ].…”

SARS-CoV-2: Reinfection after 18 Months of a Previous Case with Multiple Negative Nasopharyngeal Swab Tests and Positive Fecal Molecular Test

“…In line with previous observations [ 30 , 31 , 32 ], the oral therapy adopted was amoxicillin with clavulanic acid 3 g/day for three days and 2 g/day for another three days, associated with azithromycin 500 mg/day for six days. As supplements, he took vitamin C (2 g/day for seven days), vitamin D (25,000 I.U.…”

Biomedical Potential of the Neglected Molluscivorous and Vermivorous Conus Species

“…Furthermore, an intriguing correlation has been found between the toxin-like peptides and the samples collected from COVID-19 patients. Among all the peptides identified, conotoxin-like peptides are ubiquitous: sequences from Conus tulipa (P), Conus geographus (P), Conus marmoreus (M), Conus radiatus (V/P), Conus virgo (V), Conus quercinus (V), Conus pulicarius (V), Conus flavidus (V), Conus catus (V) and Californiconus californicus (V/M/P) have been identified in plasma, urine and fecal samples of COVID-19 patients [76]. This might explain the occurrence of many neurotic related symptoms observed in some COVID-19 patients, such as hyposmia, hypogeusia and signs typical of the Guillain-Barre syndrome.…”