Mechanisms of long-term taste loss in post-acute sequelae of COVID-19

PROJECT SUMMARY SARS-CoV-2 has infected >340 million people worldwide, including >70 million Americans. Roughly 40-45% of these patients have reported taste abnormalities. While taste function is restored quickly in many patients, recent studies show that about 10-20% of patients suffer from sustained taste loss that lasts longer than 6 months. Long-term taste loss significantly impacts health - decreasing quality of life and contributing to malnutrition, anxiety, and depression. Currently, the mechanism of long-term taste loss associated with COVID-19 infection is poorly understood, and there is no effective treatment for it. In order to develop treatment strategies, it is necessary to determine what factors contribute to long-term taste loss. Multiple antiviral mechanisms have evolved to protect us from the vast number of viral pathogens. However, these mechanisms can be weakened by genetic or environmental factors. Recent studies show that inborn genetic errors in some antiviral genes contribute to the severity of COVID-19, but whether these genetic errors also contribute to severe, long-term taste loss is unknown. In this study, we will use animal models to simulate patients with inborn genetic errors in antiviral pathways to specifically investigate whether and how these genetic defects contribute to long-term taste loss after acute COVID-19. We will further determine whether and which inflammatory factors in host immune responses inhibit taste bud regeneration and thus contribute to sustained taste loss. Mechanisms identified in this study may also apply to long-lasting symptoms in other organ systems and help to develop treatments for long-term chemosensory loss.