September 2020

New Treatment Options Focus on the Nose

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While COVID-19 is known to affect the body in numerous ways that are yet not clearly understood, several researchers have begun to focus on what is known: SARS-CoV-2, the virus that causes COVID-19, starts by infecting certain cells in the nasal passage. Stopping, or at least slowing this initial foothold may prove a powerful strategy for taming this pandemic.

Researchers are looking at inactivating certain proteins with nasal sprays, re-purposing pre-surgical nasal disinfectants, and using mists of diluted baby shampoo to disinfect the inside of the nose. And they’re looking for help from camels, llamas, and alpacas, members of the camelid family with specialized immune proteins.

Port of Entry: The olfactory epithelium, the upper back part of the nasal cavity, appears to be full of angiotensin converting enzyme 2 (ACE2), a cell needed to control hypotension. Coincidentally, this location is also where smell cells live and may explain the link between COVID-19 and loss of smell. Researcher Andrew Lane, MD, believes the signal from ACE2 in that location may provide the virus a major point of entry into the body as well as its exit to infect others. His most recent work looking at this appears in the European Respiratory Journal.1

Smothering the Spike: The image of the coronavirus with its multiple spikes is now infamous. But that spike presents an opportunity for targeting therapeutics, and researchers from the University of California, San Francisco, are working with nanobodies, specialized immune cells originally found in alpacas, camels, and llamas. These proteins are smaller than human antibodies but are believed to be hardier. Biochemist Aashish Manglik, MD, PhD, and cell biologist Peter Walter, PhD, are using nanobodies to disarm that infamous spike and prevent it from engaging with the ACE2 receptors. Doing so prevents the infection from taking hold. They hope to take this work into tests with laboratory animals and ultimately humans. A preprint of their work can be found on bioRxiv.2

Rinse It Away: Several groups are studying lower tech solutions, some of which are already in clinical trial. Researchers at the University of Kentucky have already begun a clinical trial with healthcare workers using nose sprays and gargling with povidone-iodine before and after work shifts. This preventative is based on lab studies of iodine, a common antiseptic used to treat wounds and disinfect skin before surgery. The article was published in Ear, Nose & Throat Journal.3

Another approach will be familiar to people with pollen allergies and sinus infections. This method involves washing away the virus from the nasal cavity just as saline rinses are used to remove bacteria and allergens from the nasal cavities of people with allergies. One current trial is using diluted baby shampoo with a salt mixture to determine its effects on a patient’s symptoms as well as their ability to spread the virus. This approach may wash the virus away or essentially disarm the virus and therefore inactivate it, according to Justin Turner, MD, PhD, a surgeon and rhinologist from Vanderbilt University. Interim results appear in the International Forum of Allergy & Rhinology,4 but this clinical trial is still recruiting (ClinicalTrials.gov Identifier: NCT04347538).

REFERENCES
  1. Chen M, et al. Elevated ACE2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Eur Respir J. 2020;56(3):2001948
  2. Schoof M, et al. An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation. BioRxiv.org. August 17, 2020. doi: 10.1101/2020.08.08.238469.
  3. Frank S, et al. Povidone-iodine use in sinonasal and oral cavities: A review of safety in the COVID-19 era. Ear Nose Throat J. Published online June 10, 2020. doi: 10.1177/0145561320932318.
  4. Kimura et al. Interim analysis of an open-label randomized controlled trial evaluating nasal irrigations in non-hospitalized patients with COVID-19. Int Forum Allergy Rhinology. Published online September 11, 2020. doi:10.1002/alr.22703.

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