Pandemic Proteomics

One of the major challenges we face in the fight against COVID-19 is a lack of knowledge surrounding host responses. Some are asymptomatic; others die – but what biological mechanisms underscore this chasmic disconnect?

Christoph Messner and colleagues are unraveling the mystery (1). Having spent the last few years developing an MS-based, high-throughput proteomics platform at the Francis Crick Institute, the team can quantify over 200 proteins per sample in less than 10 minutes. “It was obvious that our proteomics platform could be used as a powerful tool to study the plasma proteins of patients infected with SARS-CoV-2,” Messner says. “We set out to assess protein-level host responses with the hope of identifying markers for disease severity.”

And that’s just what they did. Samples from the first COVID-19 patients hospitalized at the Charité University Hospital in Berlin were subjected to MS-based proteomics by applying Sequential Window Acquisition of All Theoretical Mass Spectra. Interestingly, the platform uses a standard-flow ultra-high-performance LC system, rather than the usual nano-LC, to reduce run-to-run time and increase robustness. Coupled with semi-automated sample preparation, which allows the preparation of four 96-well plates in parallel, the team can analyze hundreds of samples per day.

“We found 27 biomarkers that classify mild and severe forms of COVID-19, some of which may represent therapeutic targets,” Messner says. “These proteins highlight roles for complement factors, the coagulation system, and inflammatory mediators (including proinflammatory signaling molecules up- and downstream of interleukin-6) in the SARS-CoV-2 host response.” The hope now is that these markers could be targeted in routine tests, allowing doctors to earmark patients at increased risk of critical illness.

The researchers are currently advancing their work in larger, longitudinal patient cohorts to refine the identified biomarkers and build models to predict COVID-19 progression. At the same time, they are developing multiple reaction monitoring assays to guide treatment decisions in hospitals.

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