Metabolite, protein, and tissue dysfunction associated with COVID-19 disease severity

Abstract

Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.

NucEnvDB: A Database of Nuclear Envelope Proteins and Their Interactions

“…Overall, clustering and enrichment results are in agreement with what is known about SARS-CoV-2 influencing the host’s processes, i.e., targeting and disrupting gene transcription host mRNA facilitation and transcription factor activity (Clusters 3 and 4) [ 59 ], disruptions in metabolite production (Cluster 1) [ 69 ], and hijacking the cell’s vesicle transport system (Cluster 6). What is more, they provide a potential molecular basis for these effects, as they seem to be primarily focused on the NE-localized proteins of the virus.…”

Untangling the link between the human gut microbiota composition and the severity of the symptoms of the COVID‐19 infection

“…This result is in accordance with the above taxonomical analysis and the increase of species related to putrefactive dysbiosis. Remarkably, several public studies highlighted the possible correlation between COVID‐19 disease severity and the alteration of systemic amino acid metabolism (Masoodi et al, 2022 ; Paez‐Franco et al, 2021 ; Rahnavard et al, 2022 ). In particular, the enrichment of specific amino acids, such as arginine and proline, could contribute to excessive systemic inflammation and a consequent increase in the severity of the disease (Rahnavard et al, 2022 ).…”

“…Remarkably, several public studies highlighted the possible correlation between COVID‐19 disease severity and the alteration of systemic amino acid metabolism (Masoodi et al, 2022 ; Paez‐Franco et al, 2021 ; Rahnavard et al, 2022 ). In particular, the enrichment of specific amino acids, such as arginine and proline, could contribute to excessive systemic inflammation and a consequent increase in the severity of the disease (Rahnavard et al, 2022 ). Therefore, the increased protein metabolic capability of the intestinal microbiome observed in this study could suggest the intestinal bacterial communities' contribution to systemic inflammation.…”

“…In fact, the reduction of these short-chain fatty acid-producing bacteria could increase oxidative stress and ROS production that affect the regulation of the intestinal barrier and contribute to the systemic inflammation (Wang et al, 2021). These observations were mainly obtained through the 16S rRNA gene sequencing analysis (Chen et al, 2022;Mazzarelli et al, 2021;Romani et al, 2022;Wang et al, 2021;Xu et al, 2021), whose main limit is to allow a taxonomic profiling of the microbial communities down to genus level while being inaccurate at the species level and preventing the reconstruction of functional impact of the microbiome.…”

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches

“…Compared to the non-COVID-19 and healthy groups, the 15-HETE levels identified in the COVID-19 individuals were significantly depleted. The lack of anti-inflammatory signals brought on by the reduction of 15-HETE may be a factor in the increased inflammation observed during COVID-19 infection [ 172 ]. A targeted metabolomic study analyzed and identified AMP, dGMP, sn-glycerol-3-phosphocholine, and carnitine metabolites that were dysregulated in patients with COVID-19 [ 173 ].…”