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Article ; Online: A new absolute quantitative method for peptide and metabolite detection.

Brogna, Carlo / Cristoni, Simone

2023 Volume 59, Issue 1, Page(s) e4991

Abstract: Mass spectrometry is widely employed in various analytical fields for both compound identification and quantification. While in the case of compound identification, the high-resolution instrument has increased selectivity and characterization efficiency; ...

Abstract	Mass spectrometry is widely employed in various analytical fields for both compound identification and quantification. While in the case of compound identification, the high-resolution instrument has increased selectivity and characterization efficiency; in the case of quantitative analysis, some critical tasks actually remain. In particular, different compounds exhibit different ionization efficiency, and this introduces the need to have a calibration standard for each analyte. In this paper, we present a new elaborative data technology, which makes it possible to standardize calibration between different instruments and molecules, making it absolute. The method was applied to data acquired by means of liquid chromatography mass spectrometry by means of an ion trap analyzer. The approach is based on the correlation of the ion trap space charge effect and the analyte concentration. The method was validated in the analysis of compounds having different polarity: hydrossitirosol, arginine, thyodiglicolic acid, and a peptide mixture of bacteria cultures derived the human gut microbiome where was found poliovirus. Moreover, it was used to obtain the absolute quantitation of peptides originating from the tryptic digestion of bacterial proteins in the fecal samples. It was therefore possible to identify and quantify different derived bacterial proteins of the poliomyelitis virus coded in bacteria derived from the gastrointestinal tract.
MeSH term(s)	Humans ; Research Design ; Arginine ; Bacterial Proteins ; Calibration ; Peptides
Chemical Substances	Arginine (94ZLA3W45F) ; Bacterial Proteins ; Peptides
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1221763-3
ISSN	1096-9888 ; 1076-5174
ISSN (online)	1096-9888
ISSN	1076-5174
DOI	10.1002/jms.4991
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Article ; Online: The importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2.

Brogna, Carlo / Viduto, Valentina / Fabrowski, Mark / Cristoni, Simone / Marino, Giuliano / Montano, Luigi / Piscopo, Marina

Gut microbes

2023 Volume 15, Issue 1, Page(s) 2244718

Abstract: Zhou et al. study nicely traces a significant topic in COVID-19 infection: the persistence of the virus within the intestinal tract. Many pathological mechanisms have been noted in the current literature about the mode of infection and propagation of ... ...

Abstract	Zhou et al. study nicely traces a significant topic in COVID-19 infection: the persistence of the virus within the intestinal tract. Many pathological mechanisms have been noted in the current literature about the mode of infection and propagation of SARS-CoV-2 in the human body. Nevertheless, there are still many concerns about this: only some things seem well understood. We present a different point of view by illustrating the importance of the gut microbiome in the pathogenesis of COVID-19 disorders.
MeSH term(s)	Humans ; SARS-CoV-2 ; Gastrointestinal Microbiome ; COVID-19
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2244718
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Article ; Online: A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

Brogna, Carlo / Montano, Luigi / Zanolin, Maria Elisabetta / Bisaccia, Domenico Rocco / Ciammetti, Gianluca / Viduto, Valentina / Fabrowski, Mark / Baig, Abdul M / Gerlach, Joachim / Gennaro, Iapicca / Bignardi, Elio / Brogna, Barbara / Frongillo, Aquilino / Cristoni, Simone / Piscopo, Marina

Journal of medical virology

2024 Volume 96, Issue 3, Page(s) e29507

Abstract: The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral ... ...

Abstract	The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.
MeSH term(s)	Humans ; Anti-Bacterial Agents/therapeutic use ; COVID-19/prevention & control ; Rifaximin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Retrospective Studies ; Anti-Inflammatory Agents, Non-Steroidal ; Adrenal Cortex Hormones
Chemical Substances	Anti-Bacterial Agents ; Rifaximin (L36O5T016N) ; COVID-19 Vaccines ; Anti-Inflammatory Agents, Non-Steroidal ; Adrenal Cortex Hormones
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29507
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Article ; Online: Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification.

Brogna, Carlo / Costanzo, Vincenzo / Brogna, Barbara / Bisaccia, Domenico Rocco / Brogna, Giancarlo / Giuliano, Marino / Montano, Luigi / Viduto, Valentina / Cristoni, Simone / Fabrowski, Mark / Piscopo, Marina

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been ... ...

Abstract	SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients' blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19 ; RNA ; Bacteriophages/genetics ; Amino Acids ; Proteomics ; Viruses/genetics ; Microscopy, Fluorescence
Chemical Substances	RNA (63231-63-0) ; Amino Acids
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043929
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Article: Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?

Brogna, Carlo / Brogna, Barbara / Bisaccia, Domenico Rocco / Lauritano, Francesco / Marino, Giuliano / Montano, Luigi / Cristoni, Simone / Prisco, Marina / Piscopo, Marina

Vaccines

2022 Volume 10, Issue 5

Abstract: SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal ... ...

Abstract	SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen (
Language	English
Publishing date	2022-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines10050708
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Article: A Metabolomic Analysis to Assess the Responses of the Male Gonads of

Lettieri, Gennaro / Marinaro, Carmela / Brogna, Carlo / Montano, Luigi / Lombardi, Martina / Trotta, Alessio / Troisi, Jacopo / Piscopo, Marina

Metabolites

2023 Volume 13, Issue 12

Abstract: In recent years, metabolomics has become a valuable new resource in environmental monitoring programs based on the use of bio-indicators such ... ...

Abstract	In recent years, metabolomics has become a valuable new resource in environmental monitoring programs based on the use of bio-indicators such as
Language	English
Publishing date	2023-11-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13121168
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Article: Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2-New Data for a Possible Role in the Long COVID Pattern.

Brogna, Carlo / Cristoni, Simone / Brogna, Barbara / Bisaccia, Domenico Rocco / Marino, Giuliano / Viduto, Valentina / Montano, Luigi / Piscopo, Marina

Biomedicines

2022 Volume 11, Issue 1

Abstract: It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra- ... ...

Abstract	It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson's disease (PD) or Alzheimer's Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.
Language	English
Publishing date	2022-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11010087
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Article ; Online: SARS-CoV-2: Reinfection after 18 Months of a Previous Case with Multiple Negative Nasopharyngeal Swab Tests and Positive Fecal Molecular Test.

Brogna, Carlo / Brogna, Barbara / Bisaccia, Domenico Rocco / Giuliano, Marino / Montano, Luigi / Cristoni, Simone / Petrillo, Mauro / Piscopo, Marina

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 5

Abstract: This short communication describes the reinfection after nearly 18 months of the same patient who was previously infected with coronavirus disease 2019 (COVID-19) and who showed multiple negative real-time quantitative reverse transcriptase-polymerase ... ...

Abstract	This short communication describes the reinfection after nearly 18 months of the same patient who was previously infected with coronavirus disease 2019 (COVID-19) and who showed multiple negative real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) results by nasal swabs for severe acute respiratory syndrome coronavirus (SARS-CoV-2) but positive results on a fecal sample. We previously noted how, in the presence of symptoms suggestive of pneumonia, visible on a chest computed tomography (CT) scan and confirmed by fecal molecular testing, it was possible to draw the diagnosis of SARS-CoV-2 infection. One year later, the same patient was again affected by SARS-CoV-2. This time, the first antigenic nasal swab showed readily positive results. However, the patient's clinical course appeared to be more attenuated, showing no signs of pulmonary involvement in the radiographic examinations performed. This case shows a novelty in the pulmonary radiological evaluation of new SARS-CoV-2 infection.
MeSH term(s)	COVID-19/diagnosis ; Feces ; Humans ; Nasopharynx ; Reinfection ; SARS-CoV-2
Language	English
Publishing date	2022-05-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58050642
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Article ; Online: Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms.

Brogna, Carlo / Cristoni, Simone / Marino, Giuliano / Montano, Luigi / Viduto, Valentina / Fabrowski, Mark / Lettieri, Gennaro / Piscopo, Marina

Proteomics. Clinical applications

2023 Volume 17, Issue 6, Page(s) e2300048

Abstract: Purpose: The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein ...

Abstract	Purpose: The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer. Experimental design: Mass spectrometry examination of biological samples was used to detect the presence of specific fragments of recombinant Spike protein in subjects who received mRNA-based vaccines. Results: The specific PP-Spike fragment was found in 50% of the biological samples analyzed, and its presence was independent of the SARS-CoV-2 IgG antibody titer. The minimum and maximum time at which PP-Spike was detected after vaccination was 69 and 187 days, respectively. Conclusions and clinical relevance: The presented method allows to evaluate the half-life of the Spike protein molecule "PP" and to consider the risks or benefits in continuing to administer additional booster doses of the SARS-CoV-2 mRNA vaccine. This approach is of valuable support to complement antibody level monitoring and represents the first proteomic detection of recombinant Spike in vaccinated subjects.
MeSH term(s)	Humans ; COVID-19 Vaccines ; SARS-CoV-2/genetics ; Proteomics ; Spike Glycoprotein, Coronavirus/genetics ; COVID-19/prevention & control ; RNA, Messenger/genetics ; Vaccination
Chemical Substances	COVID-19 Vaccines ; spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; RNA, Messenger
Language	English
Publishing date	2023-08-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2261788-7
ISSN	1862-8354 ; 1862-8346
ISSN (online)	1862-8354
ISSN	1862-8346
DOI	10.1002/prca.202300048
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Article ; Online: Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients.

Brogna, Carlo / Cristoni, Simone / Petrillo, Mauro / Querci, Maddalena / Piazza, Ornella / Van den Eede, Guy

F1000Research

2021 Volume 10, Page(s) 550

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	COVID-19 ; Feces ; Humans ; Pandemics ; Peptides ; SARS-CoV-2
Chemical Substances	Peptides
Language	English
Publishing date	2021-07-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.54306.2
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