Noninvasive nasopharyngeal proteomics of COVID-19 patient identify abnormalities related to complement and coagulation cascade and mucosal immune system

Ayass, Mohamad Ammar; Cao, Wanying; Zhang, Jin; Dai, Jun; Zhu, Kevin; Tripathi, Trivendra; Griko, Natalya; Pashkov, Victor; Abi-Mosleh, Lina

doi:10.1371/journal.pone.0274228

Cited by 8 publications

(4 citation statements)

References 81 publications

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“…Patients with COVID-19 have been reported to have significant alterations in oral (tongue-coating) and gut microbial diversity [ 21 – 23 ], as well as alterations in the expression level of proteins from fecal microbiomes [ 24 , 25 ], plasma human proteomes [ 26 ], nasopharyngeal swabs [ 27 – 29 ] and semen samples [ 30 ]. Proteome profiling of nasopharyngeal swabs from COVID-19 patients further revealed alterations in proteins implicated in the innate immune response, viral assembly, and exocytosis [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Moreno,

Ciordia,

Fátima

et al. 2024

Clin Proteom

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Background Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. Methods We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). Results By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. Conclusion Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Moreno,

Ciordia,

Fátima

et al. 2024

Clin Proteom

View full text Add to dashboard Cite

show abstract

“…Patients with COVID-19 have been reported to have significant alterations in the oral (tongue-coating) and gut microbial diversity [21][22][23], as well as alterations in the expression level of proteins from fecal microbiomes [24,25], plasma human proteomes [26], nasopharyngeal swabs [27][28][29] and semen samples [30]. Proteome profiling of nasopharyngeal swabs from COVID-19 patients further revealed alterations in proteins implicated in innate immune response, viral assembly, and exocytosis [31].…”

Section: Discussionmentioning

confidence: 99%

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Olmo,

Ciordia,

Santos

et al. 2023

Preprint

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The information on the microbiome’s human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied samples collected from April to June 2020 from unvaccinated patients. We compared 10 infected and hospitalized patients with severe (n=5) and moderate (n=5) Coronavirus Disease (COVID-19) with 10 uninfected individuals, including Non-COVID but susceptible individuals (n=5) and Non-COVID and non-susceptible healthcare workers with repeated high-risk exposures (n=5). By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤0.05) out of 2721 unambiguously identified proteins (false discovery rate ≤1%). Major differences were observed between the Non-COVID vs the non-susceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with saliva of SARS-CoV-2 infected patients (p-value ≤0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression level of two human proteins related to protein transport in the cytoplasm, named DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that are overrepresented in the infected group. Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility although further studies in larger cohorts will be necessary.

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“…TOP is expressed by various tissues/organs, including the lungs [103]. TOP has been proposed to be involved in COVID-19 disease [5,104,105] due to its role in converting angiotensin I to angiotensin 1-7, being able to offset the harmful effects of angiotensin II in favor of the antiinflammatory and lung protective effects of angiotensin 1-7. Thus, the potential involvement of TOP and EV-associated TOP in pathological roles in COVID-19 disease would be worthwhile to investigate.…”

Section: Extracellular Vesicles Neprilysin and Thimet Oligopeptidase ...mentioning

confidence: 99%

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

LIU,

KASPER,

CHOI

2024

BIOCELL

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Extracellular vesicles (EVs) are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions. Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells or microorganism-infected and noninfected cells.Coronavirus disease 2019 (COVID-19) disease is caused by infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of host cells in the respiratory system and various extra-pulmonary tissue/organs, resulting in complications of multiple organ systems. As the cell surface receptor, angiotensin-converting enzyme 2 (ACE2) mediates cellular entry of SARS-CoV-2 into the host cells in patients with COVID-19. Recent studies have found that ACE2 can be released with EVs, which have been shown to interfere with the entry of the virus into host cells and thus may be involved in COVID-19 pathophysiology. In addition, ACE2, neprilysin (NEP), and thimet oligopeptidase (TOP) are the key enzymes that regulate angiotensin metabolism by converting angiotensin II or angiotensin I to angiotensin 1-7, the latter of which has protective effects in counterbalancing the harmful effects of angiotensin II in COVID-19 disease. This review summarizes the recent research progress regarding EV-associated ACE2, NEP, and TOP and the perspectives of their potential involvement in the pathophysiology of COVID-19 disease.

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Noninvasive nasopharyngeal proteomics of COVID-19 patient identify abnormalities related to complement and coagulation cascade and mucosal immune system

Cited by 8 publications

References 81 publications

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

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