A Shared Interest

COVID-19 still threatens the lives of millions around the globe. Although chronic conditions such as obesity, hypertension, and kidney disease have long been established as clinical risk factors for severe outcomes, new research suggests that AMD is also a cause for concern (1). Because of the condition’s association with a higher likelihood of COVID-19 complications than type 2 diabetes or obesity, researchers from The Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 may share some common genetic risk factors.

To identify these genetic determinants, the researchers evaluated genetic correlations between AMD and COVID-19 using cross-phenotype meta-analysis (pleiotropy analysis). Obtaining summary statistics from large databases – including an AMD early genome-wide association study that included over 16,000 cases – they identified a novel association between both conditions and PDGFB gene variation. The gene, which encodes for a platelet-derived growth factor (PDGF-BB), plays a signficant role in the formation of new blood vessels and, subsequently, the abnormal blood vessel changes that occur in AMD.

As well as meta-analysis, researchers also used Mendelian randomization to investigate the relationships between PDGFB variants, Pdgfb concentrations in blood, AMD, and COVID-19 outcomes. These studies identified a causal relationship between complement pathway dysfunction in AMD and subsequent infection by – and hospitalization due to – COVID-19.

These findings suggest that lowering PDGFB expression and serum PDGF-BB concentrations may reduce the severity of COVID-19, particularly in patients aged 40 years and up. Despite the growing body of evidence that points to increased risk of COVID-19 infection and mortality in AMD patients, further research that extends into other populations is still needed. Study author Lindsay Farrer states that the next steps for this research include studies in engineered cells and animal models to get a better understanding of the mechanism behind the statistical associations.