Investigating cellular pathways driving severe COVID-19: Fresh insights from longitudinal plasma proteomics

Speakers:  Michael Filbin, Emergency Physician and Director of clinical research in the Department of Emergency Medicine at Massachusetts General Hospital (MGH) & Arnav Mehta, Postdoctoral Researcher in Nir Hacohen and Eric Lander’s labs at the Broad Institute of MIT and Harvard

Original Broadcast date:  November 18 2020

COVID-19 has caused more than 1 million deaths worldwide. Extraordinary research efforts are being made at the lab bench and in the clinic, aided by initiatives such as diverted funding, accelerated publication channels, increased collaboration, and open sharing of data. In order to accelerate research into the pandemic, the “COVID-19 Technology Access Framework” was set up by Harvard University, the Massachusetts Institute of Technology, and Stanford University, to pool resources and ensure that research findings and data are shared rapidly and openly to inform the public health response. Within this framework, researchers from Massachusetts General Hospital recently collaborated with Olink Proteomics to carry out one of the largest longitudinal COVID-19 studies to date. This study aimed to generate new insights into the mechanisms underlying immune responses and disease severity in infected patients by serial measurements of over 1,400 proteins in a cohort of ~400 SARS-CoV-2–infected patients and symptomatic controls. Hundreds of plasma proteins were found to be differentially expressed between COVID-19 patients and controls, as well as between those with mild and severe forms of the disease. Together with cellular and RNA expression analyses, the study also enabled a detailed dissection of both systemic and tissue-specific responses to SARS-CoV-2. This rich dataset of over 1.3 million protein measurements and essential clinical data has been made freely available to the scientific community to facilitate further investigation of pathways underlying severe disease—which may be the basis for early diagnosis of COVID-19 and subsequent clinical intervention.

This webinar covers the following points:

• How the levels of over 600 plasma proteins differ between infected patients and controls, with a “viral response signature” of multiple cytokines and other proteins identified
• Discover that more than 200 proteins also discriminate between severe and non-severe COVID-19, and that specific proteins are associated with survival or death in those with severe disease
• Discuss about the differential molecular and cellular immune responses to SARS-CoV-2 infection at the tissue and systemic level, and gain new insights into tissue-specific cell death signatures and cell-to-cell communication.

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