Recent evidence has emerged suggesting that age-related macular degeneration (AMD) is a clinical risk factor for increased risk of infection and mortality. AMD has been reported to confer an increased risk of serious complications of SARS-CoV-2 infection, including respiratory failure and death (25 percent), a risk that is higher than type 2 diabetes (21 percent). ) and obesity (13 percent).
Taking these observations into account, researchers at Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and designed and ran a study that identified a new association. of the two diseases with variants in the PDGFB gene. This gene encodes a platelet-derived growth factor (Pdgf) that has a role in the formation of new blood vessels and is involved in the abnormal blood vessel changes that occur in AMD. They also found that more severe COVID-19 outcomes were associated with AMD likely arising from genetic predisposition to dysfunction involving complement proteins, as well as higher blood serum Pdgf level.
Our findings add to the body of evidence for increased risk of COVID-19 infection and mortality among patients with AMD. Our analysis lends credence to previously reported clinical studies that found that people with AMD are at increased risk of COVID-19 infection and severe disease, and that this increased risk may have a genetic basis.”
Lindsay A. Farrer, PhD, chief of biomedical genetics, co-corresponding author
The BU research team conducted a genome-wide search for variants that are co-associated with AMD and each of the three COVID-19 outcomes (infection rate, critical illness, and hospitalization) using large genetic data sets containing tens of thousands of people. These data sets were previously pooled and studied separately to determine the genetic factors that contribute to AMD risk and for each of the COVID-19 disease outcomes. The researchers then analyzed publicly available data from patients with AMD or COVID-19 and control groups to assess the association of variants in PDGFB with gene activity. Finally, they used an analytical technique that allowed them to investigate the causal relationships between PDGFB genetic variants, blood Pdgfb concentration, AMD and COVID-19 results.
According to the researchers, these findings suggest that reducing PDGFB gene activity and serum PDGF concentration may reduce the severity of COVID-19, especially among older people. “Therapeutic strategies that combine anti-VEGF therapy (a current treatment for AMD that limits the growth of blood vessels in the eye that can damage vision) with antagonists (drugs that bind to receptors) to block PDGF signaling have been considered even more effective than VEGF treatment alone and are currently under investigation in clinical trials,” added co-corresponding author Manju L. Subramanian, MD, associate professor of ophthalmology..
The researchers believe that this discovery of shared genetic risk factors will require a larger sample size for critical illness and hospitalizations to better understand the shared pathology and risk factors that contribute to worsening clinical outcomes in both disease states.