Longitudinal proteomic profiling provides insights into host response and proteome dynamics in COVID‐19 progression

Abstract

In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify potential early prognostic protein markers and to expand understanding of proteome dynamics during clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early potential prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. Our findings provide some new insights into host response to SARS-CoV-2 infection, which are valuable for understanding of COVID-19 disease progression. This study also identified potential biomarkers that could be further validated, which may support better predicting and monitoring progression to severe COVID-19.

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

“…Findings suggest a role for PON1 against atherosclerosis and obesity and protective capacity against bacterial, parasitic, and viral infectious diseases (59). Regarding COVID-19, PON1 has been shown to increase in protein levels from nonsevere to severe patients (22) and we found the protein underrepresented in nonsevere and recovered patients, thus suggesting a biomarker for disease recovery. CPB2 appears to have a role in innate immunity through inactivation of complement component C5a, which can induce inflammatory pathways via C5aR receptor (41,61).…”

“…characterize host response to SARS-CoV-2 infection in different cohorts from asymptomatic individuals to severe patients. Due to the complexity of COVID-19 symptomatology, this approach contributed to a better understanding of disease mechanisms and symptoms with possible medical complications at different levels and the identification of potential diagnostic/prognostic biomarkers and drug targets (22)(23)(24)(25). The results corroborated previous findings in COVID-19 studies and highlighted how the representation of dysregulated serum proteins and associated BPs increases with COVID-19 disease symptomatology from asymptomatic to severe cases (4-6, 8-13, 18, 22-25).…”

“…Other novel prognostic biomarker proteins related to COVID-19 disease symptomatology were identified (Table 1 and Figure 7) (22,68). These biomarkers included potential prognostic tools for SARS-CoV-2 infection, disease symptomatology, progression and recovery, and reduction in thyroiditis.…”

“…However, due to the complexity of COVID-19 symptomatology, it is important to characterize host response to SARS-CoV-2 infection in different cohorts from asymptomatic individuals to severe patients to better understand disease mechanisms and symptoms with possible medical complications at different levels, and the identification of potential diagnostic markers and drug targets (22)(23)(24)(25). Quantitative proteomics approaches alone or in combination with other omics technologies are key to achieve this goal (24)(25)(26)(27).…”

Application of omics technology to combat the COVID‐19 pandemic

“… 185 , 186 , 187 In addition, there are certain proteomic analysis studies of exosomes and plasma samples, and found that a variety of cytokines including CRP, lactate dehydrogenase (LDH), procalcitonin (PCT), SAA, angiotensinogen (AGT), IL‐12, PTX3, IGLV3‐19, BNC2, CKAP4, and so on are remarkably upregulated or downregulated during the disease progression, which could serve as potential predictors of progression and mortality, although some cytokines are nonspecific and still need further confirmation. 188 , 189 , 190 , 191 , 192 , 193 , 194 Compared with nonsevere COVID‐19 patients, dysregulation of a variety of apolipoproteins (APOA1, APOA2, APOC1, etc.) in critically ill patients was discovered based on proteomic profiling, although the relationship between these proteins and the disease process needs further explanation.…”