Olfactory dysfunction constitutes a common impairment in the general population, affecting nearly 20 million in the USA and severely impairing quality of life. Unfortunately, this problem is often permanent, and no effective treatment is available at this time. Although many etiologies exist for olfactory loss, the underlying pathology is thought to be permanent damage to the olfactory bulb, nerves or basal cells of the olfactory system. Platelet-rich plasma (PRP) is an autologous treatment derived from a patient's own blood and has been found to have pro-nerve regenerative properties in animal and human studies. A small pilot study at the principal investigator's institution demonstrated improved olfactory thresholds in patients with partial olfactory loss who received PrP injections. In this randomized clinical trial, the investigators aim to further evaluate the ability of PRP injections to restore olfactory function in human subjects. Given the lack of effective current treatments, a therapeutic benefit of PrP would represent a crucial advancement in research and treatment of olfactory loss, which affects a large swath of the population.

Patients will be seen at the Stanford Sinus center, or at the newly added collaborating institution UCSD, and those with smell loss will be identified by the clinically validated patient directed survey: The UPSIT (University of Pennsylvania Smell Identification Test). They will undergo nasal endoscopy to exclude structural causes of smell loss including mass or tumor. Nasal endoscopy will be performed to exclude structural causes of olfactory, using topical anesthesia (1% phenylephrine \& 4% lidocaine topical spray). THESE ABOVE STEPS CONSTITUTE STANDARD OF CARE FOR EVALUATION OF OLFACTORY LOSS.

The timing of the initial research visit will depend on the evolution of the current covid-19 pandemic and adhere to Stanford guidelines regarding research visits. At the initial research visit, patients meeting inclusion criteria will be evaluated in a procedure room at the Stanford Sinus center. A baseline Sniffin' sticks smell test will be performed (see below). A small vial of blood will be drawn from the patient at the Blake Wilbur first floor laboratory. The research coordinator will walk the patient back to clinic along with the patient's blood smple. PRP will be isolated from the blood by the study investigator, following manufacturer instructions from the PurePRP preparation kit (Emcyte corporation), which will involve use of a centrifuge located in the clinic for this purpose. 0.5 mL of the PRP solution will be set aside for platelet quantification. From the remaining PRP solution, patients will then receive 1ml of autologous PrP or sterile saline (0.9% Sodium Chloride), which will be injected into the superior septum mucosa near the olfactory groove bilaterally. Patients will be blindfolded during injection to prevent identification of the injected specimen, and will previously be randomized in a 1:1 ratio via a random number generator. Patients will be monitored for side effects for 15 minutes. (We routinely perform nasal endoscopy with injection and associated procedures in our clinic, which patients tolerate very well.) Injections will then be performed twice more at 2-weeks and 4-weeks after the initial injection, for a total of 3 biweekly injections. ALL OF THE ABOVE STEPS ARE FOR RESEARCH PURPOSES.

The Sniffin' Sticks test is a validated, non-invasive assessment of olfactory function via presentation of scented felt pens to blindfolded patients. The output is the TDI score (threshold, discrimination, identification). The TDI score will be recorded at baseline (initial research visit), and then at 1-month and 3-months after the initial test, for a total of 3 tests. The first test will occur before the first injection, and the second test will be performed before the third injection. There will be no injection at the last (third) test. THE ABOVE VISITS ARE FOR RESEARCH PURPOSES.

The study time-line is summarized as follows Visit 1: 1st Sniffin' Sticks test, 1st injection Visit 2: 2 weeks after Visit 1, second injection Visit 3: 4 weeks after Visit 1, second test, third injection Visit 4: 3 months after Visit 1, third test