BOULDER, Colo., December 16, 2020 — An international consortium led by Medical Research Council (MRC) researchers in the UK working with SomaLogic performed the largest genetic discovery of host proteins involved in SARS-CoV-2 infection or severe COVID-19. The results are being shared via an open access platform to help investigators around the world prioritize protein targets for new or repurposed drugs to treat COVID-19. The information may also help medical researchers identify patients who are more likely to develop a serious case of COVID-19.
“The SomaScan® Assay enabled us to rapidly test for protein differences thought to be relevant for COVID-19 in samples from over 10,000 Fenland study participants, and we’re making this information freely available to help identify new or existing drugs that can be used to treat or prevent infection with SARS-CoV-2,” said Dr. Claudia Langenberg from the MRC Epidemiology Unit at the University of Cambridge, UK who led the study. “Even before our work was officially published, papers appeared on preprint servers that made use of our findings. This is exactly what we hoped to achieve.”
Viruses such as SARS-CoV-2 infect humans by binding to and hijacking host cells. For some COVID-19 patients, the body’s own defense system attacks healthy tissue causing damage to the lungs, heart and other organs. Host proteins that interact with the virus or that cause an overactive immune response can be targeted by drugs to block viral entry, inhibit viral proliferation or dampen damaging host inflammatory responses.
The study, published today in Nature Communications, describes common variations in the human genome linked to 179 proteins shown to be involved in SARS-CoV-2 infection or severe COVID-19 illness. These 179 proteins were identified with the aid of the SomaScan Assay, the most comprehensive proteomic technology available.
The team assessed these COVID-19 relevant proteins in more than 10,000 healthy participants in the Fenland study to identify genetic variants that regulate the way that they interact with SARS-CoV-2 or that may contribute to severe COVID-19 symptoms.
The Fenland Study is a cohort whose participants were born between 1950 and 1975 and lived in Cambridgeshire, UK, at the time they were recruited, and who have undergone detailed genetic profiles as well as objective measurement of resting metabolic rate, cardio-respiratory fitness, physical activity energy expenditure and body composition. The recruitment of relatively young individuals before chronic disease onset was designed to investigate early processes and pathways to metabolic disease unaffected by therapy or co-existing disease.
The team identified 220 genetic variants that associated with 97 of the 179 investigated host proteins. Among the 97 proteins, 38 are targets of existing drugs that could potentially be used to treat the virus. The researchers also established for the first time, a link between proteins related to excessive blood clotting and genetic risk of COVID-19 respiratory failure that is related to specific blood types. Anticoagulation treatment has already been shown to improve prognosis of patients with severe COVID-19.
In addition to helping prioritize drug targets and gaining deeper insights into the pathophysiology of COVID-19, the results may help medical researchers identify patients at risk of developing severe disease, so they can get the help they need earlier. The data will allow other groups to stratify populations, by blood type for example, to more quickly identify effective interventions.
Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C. “Genetic architecture of host proteins involved in SARS-CoV-2 infection,” Nature Communications 11, 6397 (2020). DOI: 10.1038/s41467-020-19996-z
Laura S. Mizoue, Ph.D.
SomaLogic seeks to deliver precise, meaningful, and actionable health-management information that empowers individuals worldwide to continuously optimize their personal health and wellness throughout their lives. This essential information, to be provided through a global network of partners and users, is derived from SomaLogic’s precise, proprietary, and personalized measurement of important changes in an individual’s proteins over time. For more information, visit www.somalogic.com and follow @somalogic on Twitter.