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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.

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.

Background Scientific evidence for the involvement of human microbiota in the development of COVID-19 disease has been reported recently. SARS-CoV-2 RNA presence in human faecal samples and SARS-CoV-2 activity in faeces from COVID-19 patients have been observed. Methods Starting from these observations, an experimental design was developed to cultivate in vitro faecal microbiota from infected individuals, to monitor the presence of SARS-CoV-2, and to collect data on the relationship between faecal bacteria and the virus. Results Our results indicate that SARS-CoV-2 replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth and it is influenced by the administration of specific antibiotics. SARS-CoV-2-related peptides have been detected in 30-day bacterial cultures and characterised. Discussion Our observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2, which, to our knowledge has not been observed or described before. These results are unexpected and hint towards a novel hypothesis on the biology of SARS-CoV-2 and on the COVID-19 epidemiology. The discovery of possible new modes of action of SARS-CoV-2 has far-reaching implications for the prevention and the treatment of the disease.

Background Scientific evidence for the involvement of human microbiota in the development of COVID-19 disease has been reported recently. SARS-CoV-2 RNA presence in human faecal samples and SARS-CoV-2 activity in faeces from COVID-19 patients have been observed. Methods Starting from these observations, an experimental design was developed to cultivate in vitro faecal microbiota from infected individuals, to monitor the presence of SARS-CoV-2, and to collect data on the relationship between faecal bacteria and the virus. Results Our results indicate that SARS-CoV-2 replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth and it is influenced by the administration of specific antibiotics. SARS-CoV-2-related peptides have been detected in 30-day bacterial cultures and characterised. Discussion Our observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2, which, to our knowledge has not been observed or described before. These results are unexpected and hint towards a novel hypothesis on the biology of SARS-CoV-2 and on the COVID-19 epidemiology. The discovery of possible new modes of action of SARS-CoV-2 has far-reaching implications for the prevention and the treatment of the disease.

Background Scientific evidence for the involvement of human microbiota in the development of COVID-19 disease has been reported recently. SARS-CoV-2 RNA presence in human faecal samples and SARS-CoV-2 activity in faeces from COVID-19 patients have been observed. Methods Starting from these observations, an experimental design was developed to cultivate in vitro faecal microbiota from infected individuals, to monitor the presence of SARS-CoV-2, and to collect data on the relationship between faecal bacteria and the virus. Results Our results indicate that SARS-CoV-2 replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth and it is influenced by the administration of specific antibiotics. SARS-CoV-2-related peptides have been detected in 30-day bacterial cultures and characterised. Discussion Our observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2, which, to our knowledge has not been observed or described before. These results are unexpected and hint towards a novel hypothesis on the biology of SARS-CoV-2 and on the COVID-19 epidemiology. The discovery of possible new modes of action of SARS-CoV-2 has far-reaching implications for the prevention and the treatment of the disease.