If all goes according to plan, Penn State University students who opt for an on-campus experience this fall will start in-person classes on Aug. 24 under the banner of a “Mask Up or Pack Up” campaign.

By returning to campus, students are agreeing to wear masks, adhere to social distancing practices and submit to random testing for COVID-19.

But “Mask Up or Pack Up” also offers a less traditional, more proactive approach to virus containment: the smell test.

“Our message is, ‘If you have sudden-onset smell loss, in the absence of other explanatory history like a head injury, the chance of you being infected is high,’” said John Hayes, a professor in the department of food science at Penn State and director of the Sensory Evaluation Center in the College of Agricultural sciences. “This is about raising awareness that smell loss is an early symptom of COVID-19.”

Hayes’ department plans to send scented scratch-and-sniff postcards to students, asking them to monitor their sense of smell. There will be other reminders throughout campus, such as flower arrangements that invite people to “smell the roses” before entering a lecture hall.

Bottom line, said Hayes: “We’re telling our community if you lose your sense of smell, you should self-isolate and immediately get tested.”

It’s advice that might help people throughout the world contain the spread of the COVID virus.

According to Danielle Reed, associate director of the Monell Chemical Senses Center in Philadelphia, the loss of the sense of smell is one of the best and earliest indicators of COVID-19.

“More COVID patients have loss of sense of smell than have a fever,” Reed said. “Yet fever is often first on the checklist of COVID symptoms and sense of smell is at the bottom, like an afterthought. We think it should be near or at the top.”

A recent study based on a worldwide survey of 25,000 patients by the Global Consortium for Chemosensory Research found that COVID-19 is more strongly associated with smell and taste than with fever, cough or shortness of breath, though the latter are the “cardinal symptoms currently highlighted by the US Centers for Disease Control and Prevention (CDC).” The study has not yet been peer-reviewed.

Several other studies have linked the loss of smell to the virus. Researchers at the Mayo Clinic reported in June that patients with COVID-19 were 27 times more likely to lose their sense of smell than people without the virus, while less than three times as likely to report fever and/or chills. Another analysis of medical records by Mayo researchers suggested that routine screening for those changes “could contribute to improved case detection in the ongoing COVID-19 pandemic.”

Proteus Duxbury, former chief technology officer for the Colorado health insurance exchange, now lives in Northern Ireland and heads service delivery for a National Health Service trust. Suffering from what seemed a mild cold in early March, Duxbury noticed he couldn’t smell or taste his meal. Luckily, a colleague passed along the then-brand-new hypothesis that COVID affected these senses, and Duxbury isolated, though he had no other disease symptoms.

“I didn’t have cough, headache, fever or shortness of breath,” said Duxbury. “But everything tasted like cardboard. The first thing I did every morning was put my head in the coffee jar and take a real deep breath. Nothing.”

Two weeks later, his sense of smell began to return; three months after that, he had a positive antibody test. Today, nearly six months after his recovery from COVID-19, Duxbury reports his senses are back but slightly dulled.

Scientists have hypothesized that the loss of smell is caused by damage to olfactory sensory neurons. The COVID virus actively attacks neighboring cells in the nasal cavity that express ACE2, a protein that acts as a receptor for the virus. In doing so, the olfactory cells may also become inflamed and “paralyzed.” Thus, the sudden inability to smell.

Because the loss of smell is an early symptom, it may be helpful in screening otherwise asymptomatic and pre-symptomatic COVID carriers, according to researchers. It is often the only symptom present in people who otherwise feel fine and don’t think of themselves as sick, leading them to unwittingly spread the virus. Though only 50% of COVID-19-positive patients list smell loss as a complaint, specific questioning leads to a significantly higher rate of around 70% to 75%, according to a study recently submitted by the Monell research team to the NIH.

Loss of smell has been tied to other upper respiratory ailments in the past, so it is not a foolproof exercise. Still, E. John Wherry, chair of the department of systems pharmacology at the University of Pennsylvania and director of the university’s Institute for Immunology, is cautiously optimistic about the potential for smell tests to help in the fight against COVID — while noting results can be misinterpreted.

“The idea is very attractive because we need testing any way we can get it and there’s just not enough to go around,” Wherry said. “The other side of the equation is that people who wake up with allergies or a hangover and can’t smell the coffee as well as they did yesterday might panic and run to urgent care for a test. It would be good to understand the costs.”

That’s why researchers stress that the loss of smell associated with COVID is not subtle. “It’s not a matter of degrees of discrimination,” Reed said. “This isn’t something you miss.”

The smell loss associated with COVID-19 is swift and utter. It could involve waking up one morning and not being able to smell your shampoo, aftershave or coffee. And it may be disorienting because it’s not typically accompanied by nasal congestion, which is how most people have experienced smell reduction in the past.

It’s also an extremely strong indicator, so there should be no second-guessing. Anyone who experiences an abrupt, unexplained loss of smell should take it seriously: Self-isolate and get tested for COVID-19.

Johan Lundström, a Swedish-based biologist with the Monell Chemical Senses Center, is using the evidence uncovered by the global consortium report to help track incipient COVID-19 outbreaks before they take hold.

Working with the Edith Wolfson Medical Center and the Weizmann Institute of Science, both in Israel, Lundström created smelltracker.org — a website that provides users with a simple daily smell test they can self-administer using five household items. Once they have chosen their set of odorants — such as cinnamon, peanut butter, mustard and coffee — respondents rate the odors with respect to pleasantness and strength.

Rather than collect personal data, smelltracker.org aggregates the responses in a neighborhood, region or city, so researchers see only trends. When an increasing number of people in those areas report they have a reduced, impaired or no sense of smell, public officials can move in with widespread PCR testing.

“This test is quick and very cheap, people like doing it, and it gives them some awareness and reassurance about their own health,” Lundström said. “It’s also very good at helping public health officials decide how and where to spend their resources to implement widespread testing using the proper COVID regime.”

Currently, smelltracker.org is being used by health officials in regions of Israel and in Italy, where citizens are encouraged to sign up. But the website is available worldwide, with instructions in 15 languages. Interest from other countries is beginning to grow.

No one is recommending that smell tests replace traditional swab or saliva testing. But Reed, Hayes and Lundström all believe that better education around this unique COVID-19 symptom will lead to greater engagement and care on the part of people who don’t feel sick themselves.

Perhaps the best part of smell testing is that it doesn’t involve discomfort or stigma, and it can easily be turned into a game. Soon, Reed said, instead of being zapped with a digital thermometer, individuals who are entering a meeting or store may be handed a card with three peel-off stickers and asked which one has a scent.

“I’m an optimist and I believe people do not want to spread this disease,” Hayes said. “Our students don’t want to. If we give them the tools to know when they might be sick, they’ll help us keep our campus safe.”

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