A Global Mass Spectrometry Coalition To Combat COVID-19

A global coalition involving over 500 scientists, known as the COVID-19 MS Coalition, was announced earlier this week in The Lancet. The coalition aims to share data on COVID-19 that is derived from mass spectrometry experiments, particularly focusing on molecular changes in patients' blood, the discovery of new biomarkers and inferring the molecular characteristic of the virus' spike protein and other antigens.

The COVID-19 MS Coalition is coordinated from the University of Manchester and consists of many of the world's leading mass spectrometry experts. Technology Networks spoke with Perdita Barran, Professor of Mass Spectrometry at the University of Manchester to gain insights on the rationale behind creating the coalition, how the researchers are collaborating and how the data will be shared and used.

Molly Campbell (MC): Can you expand on the rationale for creating the COVID-19 Mass Spectrometry Coalition? What are your key aims/ goals?

Perdita Barran (PB): Our rationale was based on being measurement scientists in a time of great need of measurement! Collectively we spent time discussing what would be the best thing we could do, and in consultation with clinicians and virologists we decided that there were two broad areas where mass spectrometry could help: namely looking for prognostic markers from bodily fluids (serum, saliva and sebum) and mapping the structure, dynamics and interactions of the viral antigens.

We decided early on that it would be critical to use the same methods for sample collection and processing wherever possible, to have national contacts to help coordinate and to catalogue outputs in one place.

Karen Steward (KS): What do you hope will be the main outputs from this coalition?

PB: I hope that we will provide large comparable datasets from multiomics studies that will indicate the progression of disease so that prognostic marker assays can be used in hospitals to help clinicians decide how to treat individuals.

We also think these "omics" data sets will uncover the mechanisms of infectivity and, in particular, give insights as to why certain individuals are more prone to severe reactions to SARS-CoV-2. We would like to find out why some underlying conditions, for example diabetes, make people more likely to need to be admitted to hospital. We also want to see why men and Black, Asian, and minority ethnic populations appear more susceptible.

All of these outputs will help with treatment but also with public health measures to protect people from infections.

For the viral antigen work, we want to understand the dynamics of the spike protein which activates on receptor binding. We also want to look at other parts of the virus machinery. Using hydrogen deuterium exchange - mass spectrometry (HDX-MS) we will map the role of the protective sugar coating on the viral spike proteins. Initial work will focus on recombinant forms of the virus and later on inactivated forms of the actual virus.

MC: For our readers that may be unfamiliar with the technology, please can you briefly explain how mass spectrometry can be utilized in the study and fight against COVID-19?

PB: Mass spectrometry methods can identify and quantify proteins, lipids and metabolites from biological fluids. By measuring these molecules in blood samples and comparing the quantities between patients, and in each patient as the disease progresses, we will be able to determine what biochemical processes occur. By looking at these changes and adding in meta data and clinical data on the individuals, we will then determine robust biomarkers.

Structural mass spectrometry methods allow us to examine the change in conformation of the protein and protein complexes. 

MC: The consortium includes members from around the globe. How are you working together and communicating to achieve the aims of the coalition?

PB: Many countries have appointed national champions to coordinate national activities. We use email and social media to update members and, certainly in the UK, we have regular video meetings. We are updating the data catalog on our website as people send us data outputs and we are working with the EU data portal on this. 

KS: How do you think data generated can best be shared in a useable, safe way?

PB: We are encouraging people to use community data repositories, for example PRIDE for proteomics, and MetaboLights for metabolomics. The metadata will of course have to be anonymized. In the UK we are collecting meta data from patients and samples according to the ISARIC protocol (which is recommended by the World Health Organization) and we have advised everyone to do this wherever possible. We are also asking members to tell us the accession numbers and a brief summary of the data sets. 

MC: What challenges exist when utilizing mass spectrometry for the study of SARS-CoV-2?

PB: The samples will have been collected under very different circumstances and stored and processed in different ways, and so the metadata may vary in quality. As the disease becomes endemic it will be easier to work with clinical leads and combine it with the clinical omics data to try to unify this – and indeed in the UK that is what we are doing. Our goal is to move from discovery to targeted mass spectrometry methods once we have sufficient samples and data. Our approach, opting to do replication studies at pace, aims to achieve this. We are also working with the national measurement lab LGC and with mass spectrometry manufacturers.

KS: After the SARS-CoV-2 pandemic has passed, do you think there could be a role for the consortium in tackling other global disease problems?

PB: I think we will all be more driven to perform research that can prevent or minimize the harm from COVID-19 and future diseases. I am deeply worried about how it will affect people in developing countries. We need also to be collaborative on public health issues. There are many serious diseases in existence that we should try to work on, adopting a more collaborative approach as opposed to competitive, for example tuberculosis and malaria.

Perdita Barran, Professor of Mass Spectrometry at the University of Manchester, was speaking to Dr Karen Steward and Molly Campbell, Science Writers, Technology Networks.