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How COVID-19 sparked an explosion in smell-loss research

Loss of sense of smell has become one of the issues most associated with COVID-19. Three years on, around 700,000 people in the UK alone are believed to have total smell loss (anosmia) caused by the virus, with around six million still experiencing some olfactory dysfunction.

So, it is easy to forget that loss of smell was not officially listed as a symptom until several weeks after the first cases emerged.

This month, those who were at the forefront of raising the alarm spoke at the Royal Society of Medicine about the battle for recognition in early 2020 and what we have learnt from the subsequent explosion in olfactory research.

“First there was a trickle and then there was a flood,” said Chrissi Kelly, who founded the UK smell-loss charity AbScent after losing her sense of smell in 2012. In the early months of 2020, when COVID-19 was becoming a global pandemic, a proliferation of online searches for smell loss drove increasing numbers of people to AbScent’s online resources. They now have 85,000 active users.

This surge in public interest – well before smell loss (anosmia) was officially recognised as a COVID-19 symptom – was also noticed in clinical settings. Professor Claire Hopkins, consultant ear, nose and throat (ENT) surgeon at Guy's Hospital and Professor of Rhinology at King's College London, said: “Sitting in a clinic one Monday morning in the middle of March [2020], four patients in a row walked in with sudden onset anosmia.

“Within days, on discussion boards across the UK, France, US, we all started to see the same pattern emerge.”

There followed what Professor Hopkins described as a “race to publish” in an area of research that had, until then, largely been neglected. She said: “One of the silver linings from the pandemic was suddenly this huge increase in the rate of publications.

“There is an explosion of research, recruitment of new researchers in the field and a huge increase in funding available, so this will likely yield novel treatments in years to come.”

Those early research projects produced some startling results. Using PCR tests, researchers were able to show that nine out of 10 people who presented with sudden onset smell loss ended up testing positive for COVID-19. When presented with the evidence, the UK government was initially reluctant to include anosmia as a symptom of COVID-19, believing it did not add anything to existing diagnostic criteria.

Undeterred, the team embarked on a public information campaign. A letter sharing the evidence, distributed on 19 March 2020, became a global media story. Professor Hopkins said: “I had no idea that, overnight, that letter would travel around the world more quickly than the virus.

“I woke up on Saturday morning to find myself on the front page of almost every newspaper around the world.”

Likewise, a ‘10-minute consultation’ written for the British Medical Journal (BMJ) was read 120,000 times within six months.

The team believe that this early communication with clinicians and an information-hungry public helped to slow transmission by encouraging those with smell loss to isolate, even before it was listed as a symptom. Then, as more results emerged, the evidence became overwhelming: “Finally, two months after the onset of the pandemic, we persuaded the government to change,” said Professor Hopkins.

Just as patients speaking up online and in clinics had first alerted researchers, ongoing relationships with those experiencing smell loss became a vital part of the puzzle. Hundreds of research papers have been produced with the involvement of patients and, through AbScent and fellow charity Fifth Sense, resources have been provided directly to patients free of charge.

Chrissi Kelly said: “When researchers come back and give us an update, everyone feels very happy. Patients want to be heard and understood.”

Professor Hopkins added: “Do not underestimate the ability of our patients to take on a huge volume of knowledge in this field.”

Besides anosmia, many more people are still living with some other olfactory dysfunction as a result of COVID-19 – most notably, a distorted sense of smell, known as parosmia. Simon Gane, consultant ENT surgeon at the Royal National Throat Nose and Ear Hospital, described this as when certain smells – commonly, roasted meat, coffee, onions, garlic, red wine, bacon and cola - become unbearably disgusting. The impact on the usually harmonious olfactory system is, he said, akin to the presence of a vuvuzela in an orchestra. Sharing his research identifying parosmia triggers on a molecular level, the expert on the condition said: “People are finding the same things disgusting if they have parosmia and that’s going to mean something.”

The treatment options for olfactory dysfunction currently on the table and those on the horizon were analysed in the final talk of the event, by Professor Thomas Hummel, Professor of Otorhinolaryngology at the University of Dresden Medical School in Germany.  Promising lines of enquiry for treatments, he summarised, include sodium citrate and other calcium chelators, vitamin A, omega 3, and platelet rich plasma.

Ending her talk with a message of hope for the future, Professor Hopkins suggested the greatest gift for researchers is time: “We know that two years isn't the end, and we need to be looking at patients five, 10 years from now. There is good evidence of ongoing recovery up to and beyond two years. So even our long-haul patients should remain hopeful and we should never shatter that by telling them that their loss is permanent.

“We've learned much about the pathophysiology of smell loss that will then generate new treatments.”

‘Treatments and advances in olfactory dysfunction’ was held at the Royal Society of Medicine on Friday 3 February 2023. It was organised by the RSM Laryngology and Rhinology Section, whose President Professor Peter Andrews hosted and chaired the session.

The RSM is grateful for the support of KARL STORZ Endoscopy (UK) Ltd and Medtronic Limited, annual sponsors for the Section’s 2022/23 academic programme.

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