Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection

Several elements have an impact on COVID-19, including comorbidities, age and sex. To determine the protein profile changes in peripheral blood caused by a SARS-CoV-2 infection, a proximity extension assay was used to quantify 1387 proteins in plasma samples among 28 Finnish patients with COVID-19 with and without comorbidities and their controls. Key immune signatures, including CD4 and CD28, were changed in patients with comorbidities. Importantly, several unreported elevated proteins in patients with COVID-19, such as RBP2 and BST2, which show anti-microbial activity, along with proteins involved in extracellular matrix remodeling, including MATN2 and COL6A3, were identified. RNF41 was downregulated in patients compared to healthy controls. Our study demonstrates that SARS-CoV-2 infection causes distinct plasma protein changes in the presence of comorbidities despite the interpatient heterogeneity, and several novel potential biomarkers associated with a SARS-CoV-2 infection alone and in the presence of comorbidities were identified. Protein changes linked to the generation of SARS-CoV-2-specific antibodies, long-term effects and potential association with post-COVID-19 condition were revealed. Further study to characterize the identified plasma protein changes from larger cohorts with more diverse ethnicities of patients with COVID-19 combined with functional studies will facilitate the identification of novel diagnostic, prognostic biomarkers and potential therapeutic targets for patients with COVID-19.

Automated summary

Using a proximity extension assay, the study quantified 1387 proteins in plasma samples from 28 Finnish patients with COVID-19 and their controls to determine the protein profile changes caused by SARS-CoV-2 infection. The findings revealed altered immune signatures in patients with comorbidities and the identification of novel elevated proteins, anti-microbial activity proteins, and extracellular matrix remodeling proteins. Additionally, downregulation of RNF41 was observed in patients compared to healthy controls. These plasma protein changes provide insights into SARS-CoV-2 infection and potential biomarkers for diagnosis, prognosis, and therapeutic targets.