Abstract
The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/. Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.
Highlights
This study explored the changes in protein expression between four disease groups where patients were either controls or had mild, severe or critical symptoms of COVID-19
Over 75% of proteins measured in this study are significantly perturbed in COVID-19 cases compared to COVID-19 negative controls of similar age groups
The results of this study indicate that astrocytic activation and/or injury (GFAP) may be a common feature in mild and severe stages of COVID-19, while neuronal injury (NfL) occurs later in the disease process and mainly in patients with critical symptoms[8]
Summary
The patients in this study originates from a previous published study, with this study including more patients and generating additional d ata[8]. Fifty-nine patients with confirmed COVID-19 and 28 healthy, agematched controls were included. Samples were collected at diagnosis and repeated when possible. Patients were divided into three groups related to systemic disease severity: 26 patients with mild (i.e., not requiring hospitalization) 9 with severe (hospitalized and requiring oxygen supplementation), and 24 with critical disease (admitted to intensive care unit [ICU] and placed on mechanical ventilation [n = 23] or not considered a candidate for ICU treatment and with fatal outcome [n = 1]). Follow-up samples on patients with critical COVID-19 were collected when they were still in ICU
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