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

Abstract

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.

The human host response to monkeypox infection: a proteomic case series study

“…The plasma proteome has similarly been shown to distinguish between different degrees of disease severity in other viral infections, including ebola [47] and COVID-19 [15][16][17]19,20]. To investigate to which degree this classification is due to a similar or divergent set of protein markers, we compared the MPX proteome response to that of an age-and sex-matched group of patients with moderately symptomatic COVID-19 (hospitalized, but without need of supplemental oxygen).…”

“…Mass-spectrometry-based proteomics is one of the emerging technologies in this regard, which due to the technical and analytical advances during the last years is increasingly moving into clinical application [11][12][13][14]. In the early phase of the COVID-19 pandemic, proteomic analyses provided rapid insights into the nature of the human response to SARS-CoV-2 and captured hallmarks of its immune evasion strategies and pathophysiology, including its impact on the complement system, coagulation cascade, and inflammatory and nutritional response machinery [12,[15][16][17][18][19]. Furthermore, proteomic signatures turned out to accurately classify disease severity in COVID-19 and allow for outcome prediction weeks in advance [19][20][21].…”

“…In the early phase of the COVID-19 pandemic, proteomic analyses provided rapid insights into the nature of the human response to SARS-CoV-2 and captured hallmarks of its immune evasion strategies and pathophysiology, including its impact on the complement system, coagulation cascade, and inflammatory and nutritional response machinery [12,[15][16][17][18][19]. Furthermore, proteomic signatures turned out to accurately classify disease severity in COVID-19 and allow for outcome prediction weeks in advance [19][20][21]. Recently, we were able to show the strength of mass-spectrometry-based proteomics for rapid translation to medical care by generating a routine-applicable proteomic biomarker panel which predicted COVID-19 severity and outcome in a multi cohort study [22].…”

The human host response to monkeypox infection: a proteomic case series study

“…In the early phase of the COVID‐19 pandemic, proteomic analyses provided rapid insights into the nature of the human response to SARS‐CoV‐2 and captured hallmarks of its immune evasion strategies and pathophysiology, including its impact on the complement system, coagulation cascade, and inflammatory and nutritional response machinery (D'Alessandro et al , 2020; Messner et al , 2020; Shen et al , 2020; Demichev et al , 2021; Overmyer et al , 2021; Nuñez et al , 2022). Furthermore, proteomic signatures turned out to classify disease severity in COVID‐19 and allow for outcome prediction weeks in advance (Völlmy et al , 2021; Demichev et al , 2022; Nuñez et al , 2022). Recently, we were able to show the strength of mass spectrometry‐based proteomics for rapid translation to medical care by generating a routine‐applicable proteomic biomarker panel which predicted COVID‐19 severity and outcome in a multicohort study (Wang et al , 2022a).…”

“…Mass spectrometry‐based proteomics is one of the emerging technologies in this regard, which due to the technical and analytical advances during the last years is increasingly moving into clinical applications (Liotta et al , 2001; Messner et al , 2020; Struwe et al , 2020; He et al , 2022). In the early phase of the COVID‐19 pandemic, proteomic analyses provided rapid insights into the nature of the human response to SARS‐CoV‐2 and captured hallmarks of its immune evasion strategies and pathophysiology, including its impact on the complement system, coagulation cascade, and inflammatory and nutritional response machinery (D'Alessandro et al , 2020; Messner et al , 2020; Shen et al , 2020; Demichev et al , 2021; Overmyer et al , 2021; Nuñez et al , 2022). Furthermore, proteomic signatures turned out to classify disease severity in COVID‐19 and allow for outcome prediction weeks in advance (Völlmy et al , 2021; Demichev et al , 2022; Nuñez et al , 2022).…”