Mapping the Serum Proteome of COVID-19 Patients; Guidance for Severity Assessment.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose outbreak in 2019 led to an ongoing pandemic with devastating consequences for the global economy and human health. According to the World Health Organization, COVID-19 has affected more than 481 million people worldwide, with 6 million confirmed deaths. The joint efforts of the scientific community have undoubtedly increased the pace of production of COVID-19 vaccines, but there is still so much uncharted ground to cover regarding the mechanisms of SARS-CoV-2 infection, replication and host response. These issues can be approached by proteomics with unprecedented capacity paving the way for the development of more efficient strategies for patient care. In this study, we present a deep proteome analysis that has been performed on a cohort of 72 COVID-19 patients aiming to identify serum proteins assessing the dynamics of the disease at different age ranges. A panel of 53 proteins that participate in several functions such as acute-phase response and inflammation, blood coagulation, cell adhesion, complement cascade, endocytosis, immune response, oxidative stress and tissue injury, have been correlated with patient severity, suggesting a molecular basis for their clinical stratification. Eighteen protein candidates were further validated by targeted proteomics in an independent cohort of 84 patients including a group of individuals that had satisfactorily resolved SARS-CoV-2 infection. Remarkably, all protein alterations were normalized 100 days after leaving the hospital, which further supports the reliability of the selected proteins as hallmarks of COVID-19 progression and grading. The optimized protein panel may prove its value for optimal severity assessment as well as in the follow up of COVID-19 patients.

Progress Identifying and Analyzing the Human Proteome: 2021 Metrics from the HUPO Human Proteome Project.

The 2021 Metrics of the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 357 (92.8%) of the 19 778 predicted proteins coded in the human genome, a gain of 483 since 2020 from reports throughout the world reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 478 to 1421. This represents remarkable progress on the proteome parts list. The utilization of proteomics in a broad array of biological and clinical studies likewise continues to expand with many important findings and effective integration with other omics platforms. We present highlights from the Immunopeptidomics, Glycoproteomics, Infectious Disease, Cardiovascular, Musculo-Skeletal, Liver, and Cancers B/D-HPP teams and from the Knowledgebase, Mass Spectrometry, Antibody Profiling, and Pathology resource pillars, as well as ethical considerations important to the clinical utilization of proteomics and protein biomarkers.

Research on the Human Proteome Reaches a Major Milestone: >90% of Predicted Human Proteins Now Credibly Detected, According to the HUPO Human Proteome Project.

According to the 2020 Metrics of the HUPO Human Proteome Project (HPP), expression has now been detected at the protein level for >90% of the 19 773 predicted proteins coded in the human genome. The HPP annually reports on progress made throughout the world toward credibly identifying and characterizing the complete human protein parts list and promoting proteomics as an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2020-01 classified 17 874 proteins as PE1, having strong protein-level evidence, up 180 from 17 694 one year earlier. These represent 90.4% of the 19 773 predicted coding genes (all PE1,2,3,4 proteins in neXtProt). Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), was reduced by 230 from 2129 to 1899 since the neXtProt 2019-01 release. PeptideAtlas is the primary source of uniform reanalysis of raw mass spectrometry data for neXtProt, supplemented this year with extensive data from MassIVE. PeptideAtlas 2020-01 added 362 canonical proteins between 2019 and 2020 and MassIVE contributed 84 more, many of which converted PE1 entries based on non-MS evidence to the MS-based subgroup. The 19 Biology and Disease-driven B/D-HPP teams continue to pursue the identification of driver proteins that underlie disease states, the characterization of regulatory mechanisms controlling the functions of these proteins, their proteoforms, and their interactions, and the progression of transitions from correlation to coexpression to causal networks after system perturbations. And the Human Protein Atlas published Blood, Brain, and Metabolic Atlases.

Why Does COVID-19 Affect Patients with Spinal Cord Injury Milder? A Case-Control Study: Results from Two Observational Cohorts.

The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well.

Why Does COVID-19 Affect Patients with Spinal Cord Injury Milder? A Case-Control Study: Results from Two Observational Cohorts

The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well.

Proteomics Insights Into the Molecular Basis of SARS-CoV-2 Infection: What We Can Learn From the Human Olfactory Axis.

Like other RNA viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in host cells, continuously modulating the molecular environment. It encodes 28 multifunctional proteins that induce an imbalance in the metabolic and proteostatic homeostasis in infected cells. Recently, proteomic approaches have allowed the evaluation of the impact of SARS-CoV-2 infection in human cells. Here, we discuss the current use of proteomics in three major application areas: (i) virus-protein interactomics, (ii) differential proteotyping to map the virus-induced changes in different cell types, and (iii) diagnostic methods for coronavirus infectious disease 2019 (COVID-19). Since the nasal cavity is one of the entry sites for SARS-CoV-2, we will also discuss the potential application of olfactory proteomics to provide novel insights into the olfactory dysfunction triggered by SARS-CoV-2 in patients with COVID-19.