Targeting the Nose

Targeting the nose: Sleeper, Woody Allen, 1973

Tuesday, April 10, 2022

In COVID news, the focus is on the nose: the promise of a nose spray to prevent COVID, spraying virus into volunteers’ noses to GIVE them COVID, and looking at how COVID makes you lose your sense of smell. So let’s take a look at the nose news.

According to a recent article in the Scientific American, eight nasal sprays are in development right now and three are in advanced trials. As with the vaccines, various versions of the viral antigens are used to elicit an immune response, such as spike proteins, virus-vectored vaccines, or live attenuated virus. While spraying fluid up your nose may sound simpler than a series of shots in the arm, developing a safe and effective nasal spray has its challenges.

1. The immunological responses of the nasal mucosa are not as well understood as the response of antibodies formed in the circulatory system induced by a vaccination in the arm.
2. The immunological barriers are harder to penetrate. The nasal mucosa is designed to keep foreign intruders out, and it does a good job.
3. The nasal passages are close to the brain, raising the concern of neurological damage.

On the other hand, IN (intranasal) vaccines have distinct advantages. By targeting the point of entry (i.e. the nose), nasal vaccines may be more effective than injections at preventing post-vaccination infection and spreading of COVID. The vaccines designed by Codagenix and Meissa use a live-attenuated virus, resulting in a broader immune response which can be effective against viral variants, as opposed to vaccines based on specific spike proteins. The IN vaccines are easier to store and administer than the current IM (intramuscular) vaccines.

Oxford-Astrazeneca’s IN vaccine is in phase I clinical trials, both as a sole source of immunity and as a booster after an initial injection dose of vaccine.

How soon can we have these IN vaccines? How long do they last? I couldn’t pin these down. The clinical trials are just getting underway, so my best guess is that it will be a year or two before we know.

When volunteers offer to get COVID for research purposes, where do they plant the virus? Up their nose, of course. But the researchers administer a 10-micron droplet through a small tube instead of a spray. Starting in March 2021, 36 volunteers between 18-30 were inoculated with virus and monitored 24 hours a day. 18 developed COVID, two of whom had no symptoms. Five volunteers lost their sense of taste and smell for six months and one still had those senses diminished after 9 months.

These studies at the Imperial College of London are producing information about viral load, when testing turns positive, and the effect of virus on blood and tissue samples taken over time. The research team plans further studies using the Delta Variant and vaccinated volunteers.

COVID Smell Disorders, from 13WTHR (link below)

Loss of taste and smell has become a familiar symptom of COVID, both early and late. The actual cause has been traced to neurological and vascular disfunction in the olfactory bulb at the base of the brain. The University of Maryland study published in JAMA in April, 2022, correlated the patients’ reported sense of smell and taste with post-mortem studies of their olfactory bulb. Since viral particles were not found in the brain tissue, the neurological and microvascular damage appear to be due to inflammation caused by the disease, rather than from direct viral infection.

The extent of the damage did not correlate with age of the patient nor with length or severity of the disease. In some cases, the damage was severe enough to be considered permanent. As with the volunteer studies above, further studies are planned to evaluate the effects of the Delta and Omicron variants.

The knowledge we’re gaining is valuable, but always with the caveat that we’re aiming at a moving target. All the initial studies mentioned above started with cases that predated the Delta variant, which peaked in the fall of 2021, and the Omicron variant, which peaked in January-February, 2022. We have the same situation with the vaccines which were in clinical trials before Delta was at its peak in the fall of 2021 and were being administered in the spring of 2021.

By the time research studies on Delta and Omicron are completed, new variants will be displacing the known ones. Testing new vaccines or studying the effects of COVID in volunteers work in real time. And so does the virus.

Today’s Notable Headlines

“‘That meatball tastes like gasoline’ | Months after getting COVID, thousands develop strange smell and taste disorders,” 13WTHR, April 29, 2021. https://www.wthr.com/article/news/investigations/13-investigates/that-meatball-tastes-like-gasoline-months-after-getting-covid-thousands-develop-strange-smell-and-taste-disorders-coronavirus-13-investigates-indiana/531-e1e994c2-1f2d-4b52-bea8-57aedea4fb5a

“Nose Spray Vaccines Could Quash COVID Virus Variants,” Scientific American, May 3, 2022. https://www.scientificamerican.com/article/nose-spray-vaccines-could-quash-covid-virus-variants/

“34 Volunteers Chose to Get Covid. Here’s What Scientists Learned.” Washington Post, May 7, 2022. https://www.washingtonpost.com/business/34-volunteers-chose-to-get-covid-heres-what-scientists-learned/2022/05/07/70de3f10-cdff-11ec-b7ee-74f09d827ca6_story.html

“First human challenge trial shows how COVID-19 strikes,” Medical Xpress, April 1, 2022. https://medicalxpress.com/news/2022-04-human-trial-covid-.html

“Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19,” JAMA Neurology. April 11, 2022. https://jamanetwork.com/journals/jamaneurology/fullarticle/2790735

Additional Sources

“COVID-19 vaccine tracker and landscape,” World Health Organization, May 5, 2022. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

“Codagenix Intranasal COVID-19 Vaccine Shows Potent Cellular Immune Response Against Conserved Viral Proteins, Indicating Potential for Immunogenicity Against Omicron and Future Variants in Phase 1 Data,” Codagenix Press Release, March 17, 2022. https://codagenix.com/codagenix-intranasal-covid-19-vaccine-shows-potent-cellular-immune-response-against-conserved-viral-proteins-indicating-potential-for-immunogenicity-against-omicron-and-future-variants-in-phase-1-dat/

“Codon Deoptimization for Live Attenuated Vaccine Candidates,” Meissa, https://www.meissavaccines.com/technology

https://www.biopharma-reporter.com/Article/2021/10/26/Could-AstraZeneca-s-COVID-19-vaccine-be-just-as-effective-via-intranasal-delivery?utm_source=copyright&utm_medium=OnSite&utm_campaign=copyright

Why am I doing this?

The pandemic hit like a tsunami and the ripple effect will be felt for decades. World upheavals, deglobalization, housing shortages, the Great Resignation, supply chain disruptions–we’re navigating changes not entirely caused by the pandemic, but accelerated by it. Since March 11, 2020, this blog has examined the modern pandemic experience in the media and in everyday life, drawing on my experience as a medical technologist, a historian, and an ordinary person living through extraordinary times.