Why Covid-19 Patients Are Suffering From Distorted and Phantom Smells

On a perfect August night, Carol Pitz, a career consultant from Chanhassen, Minnesota, was looking forward to her 25th wedding anniversary dinner, especially because she and her family had spent much of the spring isolating after exhibiting symptoms of Covid-19. She woke up one morning in March, and couldn't smell or taste anything, then developed a mild cough and fatigue. Not sick enough to be tested at the time, she and her family later tested positive for antibodies to SARS-CoV-2.

Months later, Pitz and her husband were seated at a table overlooking the lake at her favorite restaurant. She ordered the special sea bass and Brussel sprouts, and the dish looked lovely when it arrived. But after a few bites, Pitz had to stop eating. Instead of smelling her food, she was overcome by a foul, and hard-to-describe scent. “It's a unique smell,” she says. “I don't even know what it is. It's like a combination of burnt toast, and something just icky enough to make me sick to my stomach.”

What happened to Pitz is not unique. Of more than 4,000 respondents to a multilingual, international study of people with recent smell loss published in Chemical Senses in June, 7 percent reported parosmia, or odor distortion. Facebook support groups dedicated to parosmia and phantosmia, the clinical names for specific smell disorders, have grown drastically in the past few months. Instead of a scentless world, an increasing number of people who lost their sense of smell because of Covid-19 are complaining that things just don’t smell right.

They no longer wake up and can’t smell the coffee; because of parosmia, their coffee smells like burning rubber or sewage. Parosmia is most often an unpleasant smell, a distortion of an actual odor, making many foods smell and taste revolting. Phantosmia is more random, occurring without a scent trigger, uninvited and unwanted. Phantosmias, which can be fleeting or linger, are also usually foul smells, often cigarette smoke or burning wood—or for one poster on Reddit, “everything smells like a more disgusting version of Spaghetti O’s.”

Zara M. Patel, the director of endoscopic skull base surgery at the Stanford School of Medicine, has been studying olfactory dysfunction for more than a decade. It’s not unusual, she says, for smell distortions to accompany or follow smell loss. “There are so many viruses that can cause smell loss, not only other coronaviruses, but also influenza viruses and rhinoviruses,” she says. “Many of these viruses also will lead to a parosmia and phantosmia, either as part of the initial deficit, or as the nerves try and recover, but make aberrant connections.”

Smell loss, or anosmia, is such a prevalent symptom of Covid-19 it can be used for diagnosis. A May study in the Annals of Internal Medicine found 86 percent of the Covid-positive patients experienced smell loss. Most people who suffer from sudden onset anosmia from the SARS-CoV-2 infection recover their smell quickly, within four weeks for 89 percent of those in a recent study in JAMA Otolaryngology. But the remaining 10 percent continued to experience smell loss or distortions.

Researchers worldwide have been working at warp speed to unravel the mysteries of the SARS-CoV-2 virus in a flurry of preprints and shared data, with a spotlight on the chemical senses, a niche and often overlooked area of study. Early in the pandemic, researchers found that the virus needs to latch on to two proteins, ACE2 and TMPRSS2, found in many parts of the body, including the nose. This suggested that the virus could damage the olfactory neurons which relay aroma information from nose to brain. This July in Science Advances, researchers from Harvard Medical School reported that through bulk sequencing of mouse, non-human primate and human olfactory cells, they located a source of these proteins on the sustentacular cells, which support the olfactory receptor neurons and help transport odor information through the nasal mucus.

“SARS-CoV-2 binds to ACE receptors, which are present in the basal cells, supporting cells and perivascular cells around the neurons in the olfactory epithelium,” says Patel. “So although the neuron itself is not damaged, all the support structure around it is.”

“Those cells that support the regenerative capacity are the ones that suffer,” she says. “We also know that nerves do not function very well within an inflammatory environment. So because of all those reasons, it is not surprising this virus causes smell dysfunction.”

The good news, says Nancy Rawson, vice president and associate director at Monell Chemical Senses Center, a non-profit interdisciplinary research institute in Philadelphia, is that cells in the olfactory epithelium can regenerate after they have been damaged. But that regeneration can take time—up to two years, or more. “If it's affecting mature neurons, then the immature neurons need to mature fully and connect to the olfactory bulb,” she says. “Then the next wave of neurons needs to be generated to continue that process.”

Rawson says that because the brain is receiving incomplete smell information, “when the recovery process is happening in patches, or recovery is partial in different regions, you may go through that stage of parosmia on the way to a fuller recovery.”

The foul smells that characterize parosmia and phantosmia are often triggered by certain foods or smells. According to the first large study of patients with parosmia, published in 2005, the main culprits are gasoline, tobacco, coffee, perfumes and chocolate. For Pitz, coffee, chocolate and red wine smell and taste awful.

Cincinnati resident Nick Roosa shares the same triggers. He started a Facebook Covid-19 smell loss support group after he lost his sense of smell in March. He began suffering from parosmia about two months ago and says, “any food cooked with vegetable oil such as tortilla chips, French fries, chicken wings, tater tots—basically a typical American restaurant's appetizer menu—has a good chance of triggering these smell distortions.”

As of now, doctors have little relief to offer. In the past, clinicians have deployed antipsychotic, antimigraine, and antiseizure medications, corticosteroids, transcranial stimulation and even topical cocaine for relief from phantosmia and parosmia. An international group of olfactory experts writing in Rhinology advised that no definitive evidence can be found for the efficacy of any specific medical treatment for smell disorders.

But breakthroughs may be forthcoming. Because of the prevalence of smell disorders with Covid-19, more groups are showing interest in the chemosensory sciences. A global coalition of 500-plus scientists have formed the Global Consortium of Chemosensory Researchers, dedicated to open science, data sharing and interdisciplinary research to investigate the connection between the chemical senses and Covid-19. A team at Georgia State University compiled datasets of more than 602 million individual tweets about Covid-19 symptoms since March 10 that are openly available. The Mount Sinai Center for Post-COVID Care in New York is addressing “long-hauler” smell disorders in a clinical trial of fish oil. In the United Kingdom, Jane Parker, an associate professor of flavor chemistry at the University of Reading, is studying the chemistry of parosmia triggers in a research project with AbScent, a smell loss charity.

It’s been six months since Pitz lost her sense of smell, and three months since she developed parosmia. She has started to accept the changes, but laments, “People don’t understand,” she says. “The emotional parts of it are really hard to explain … when some of your favorite parts of life, like chocolate and coffee, are now all so distorted.”