R01DC019769

Innate Immune Responses to SARS-CoV-2 Infection in the Olfactory Epithelium - Research Summary

Sudden-onset of olfactory loss has been recognized as a common COVID-19 symptom. The mechanism of COVID-19 related olfactory dysfunction is unknown. Whether the degree of olfactory deficit is indicative of any long-term neurological diseases in COVID-19 has not been evaluated.

Recent single-cell RNA-seq analyses revealed that the receptor for SARS-CoV-2, ACE2, is not expressed by olfactory sensory neurons (OSNs) but are expressed by supporting sustentacular (SUS) cells in the OE. Therefore, SUS cells may be the entry cell type for SARS-CoV-2 in the OE. SARS-CoV-2 infection in the OE needs to be further characterized.

Current observations indicate that the viral infection is sparse and localized. Widespread olfactory receptor downregulation has been reported under viral infection suggesting that there might be a distributed viral impact from localized viral infection in the OE. We hypothesize that widespread SUS cell-mediated inflammatory response, triggered by SARS-CoV-2, is responsible for COVID-19 associated olfactory loss.

In this study, we will characterize inflammatory responses to SARS-CoV-2 in the olfactory epithelium and identify SUS cell-specific cytokine expressions. We will establish a primary SUS cell culture system to examine viral recognition pathways and transcription factors involved in SARS-CoV-2 induced innate immune responses. We will further determine SARS-CoV-2 infection-induced olfactory sensory neuron functional deficits.

Through this study, we will gain mechanistic insight into COVID-19 associated olfactory loss.

Davis University Of California

TO INVESTIGATE SOLUTIONS TO PROBLEMS DIRECTLY RELEVANT TO INDIVIDUALS WITH DEAFNESS OR DISORDERS OF HUMAN COMMUNICATION IN THE AREAS OF HEARING, BALANCE, SMELL, TASTE, VOICE, SPEECH, AND LANGUAGE. THE NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS (NIDCD) SUPPORTS RESEARCH AND RESEARCH TRAINING, INCLUDING INVESTIGATION INTO THE ETIOLOGY, PATHOLOGY, DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES, PRIMARILY THROUGH THE SUPPORT OF BASIC AND APPLIED RESEARCH IN ANATOMY, AUDIOLOGY, BIOCHEMISTRY, BIOENGINEERING, EPIDEMIOLOGY, GENETICS, IMMUNOLOGY, MICROBIOLOGY, MOLECULAR BIOLOGY, THE NEUROSCIENCES, OTOLARYNGOLOGY, PSYCHOLOGY, PHARMACOLOGY, PHYSIOLOGY, PSYCHOPHYSICS, SPEECH-LANGUAGE PATHOLOGY, AND OTHER SCIENTIFIC DISCIPLINES. THE NIDCD SUPPORTS: (1) RESEARCH INTO THE EVALUATION OF TECHNIQUES AND DEVICES USED IN DIAGNOSIS, TREATMENT, REHABILITATION, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES; (2) RESEARCH INTO PREVENTION AND EARLY DETECTION AND DIAGNOSIS OF HEARING LOSS AND SPEECH, VOICE, AND LANGUAGE DISORDERS AND RESEARCH INTO PREVENTING THE EFFECTS OF SUCH DISORDERS BY MEANS OF APPROPRIATE REFERRAL AND REHABILITATION; (3) RESEARCH INTO THE DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES IN THE ELDERLY POPULATION AND ITS REHABILITATION TO ENSURE CONTINUED EFFECTIVE COMMUNICATION SKILLS; AND (4) RESEARCH TO EXPAND KNOWLEDGE OF THE EFFECTS OF ENVIRONMENTAL AGENTS THAT INFLUENCE HEARING OR OTHER COMMUNICATION PROCESSES.

93.173 - Research Related to Deafness and Communication Disorders

National Institute on Deafness and Other Communication Disorders (NIDCD) [HHS - NIH]

Davis, California 95618 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 500% from $586,386 to $3,517,083.