There is growing evidence that age-related macular degeneration (AMD) is a clinical risk factor for higher mortality and infection rates. AMD has been reported to a higher chance of developing serious complications of SARS-CoV-2 infection-, such as respiratory failure and mortality (25%)—a risk that is higher than that of Type 2 diabetes (21%) and obesity (13%).
Based on these findings, researchers from Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and carried out a study that discovered a novel association between the two diseases and variants in the PDGFB gene.
This gene encodes a platelet-derived growth factor (Pdgf), which is involved in the abnormal blood vessel changes that occur in AMD. They also discovered that more severe COVID-19 cases were linked to AMD, most likely due to a genetic predisposition to complement protein dysfunction, as well as a greater quantity of Pdgf in the serum.
"Our findings add to the body of evidence for the increased risk of infection and mortality from COVID-19 among AMD patients. Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis," explained co-corresponding author Lindsay A. Farrer, Ph.D., chief of biomedical genetics.
Using huge genetic databases containing tens of thousands of individuals, the BU research team conducted a genome-wide search for variants that are jointly related with AMD and each of three COVID-19 outcomes (infection rate, serious illness, and hospitalization). These datasets were previously collected and investigated separately for genetic variables associated with AMD risk and each of the COVID-19 disease outcomes.
Then, the researchers reviewed publically accessible data from patients with AMD or COVID-19, as well as control groups, to assess the correlation of PDGFB variants with gene activity. Finally, they used an analytical technique to look into the relationships between PDGFB gene variants, PDGFB levels in blood, AMD, and COVID-19 results.
According to the study, these findings suggest that reducing PDGFB gene activity and serum PDGF levels may reduce the severity of COVID-19, especially in elderly adults.
"Therapeutic strategies combining anti-VEGF therapy (a current treatment for AMD that limits blood vessel growth in the eye that can harm vision) with antagonists (drugs that bind to receptors) for blocking PDGF signaling have been considered even more effective than the single VEGF treatment and are currently under investigation in clinical trials," added co-corresponding author Manju L. Subramanian, MD, associate professor of ophthalmology.
The researchers believe that the discovery of common genetic risk factors will require a bigger sample size for critical illness and hospitalizations in order to better understand the shared pathology and risk factors that lead to worsened clinical outcomes in both disease states.
Reference: Jaeyoon Chung et al, Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes, Journal of Clinical Medicine (2022). DOI: 10.3390/jcm12010109