17 Feb, 2021

Exploring Long COVID: February 2021

We share a monthly summary of the latest Long COVID research and findings.

It's February already, and we’re in the midst of a serious resurgence of the coronavirus pandemic. Many of us are living under lockdown conditions and our lives often feel limited and confined.  

Yet, there’s a glimmer of hope for the coming year. Vaccines are being rolled out as speedily as possible in many countries and it’s heartening to know that, at the time of writing, more than 130 million COVID-19 vaccine doses have already been administered globally.

Unfortunately, 2021 may be trickier to navigate for Long COVID sufferers. “Long-haulers”, as they’re sometimes known, continue to experience perplexing and life-impacting symptoms following COVID-19 infection.

“Long-haulers” are asking for more

Long COVID guidelines for GPs and health professionals were published and signed by the National Institute for Clinical Excellence (NICE), the Royal College of General Practitioners (RCGP) and the Scottish Intercollegiate Guidelines Network (SIGN) on 18 December 2020.

COVID long-haulers, however, are saying these guidelines don’t accurately reflect their “lived experience”. The UK doctors #Longcovid support group recently published an article in the Lancet medical journal criticising the NICE guidelines. Its authors believe the guidelines are “overly focused on self-management, psychological support, and rehabilitation, resulting in the potential for ‘watered-down’ versions of NHS Long COVID clinics that do not provide thorough physical assessment of patients.” 

Long COVID isn’t going anywhere, but sufferers are increasingly self-advocating and being heard and that’s certainly a promising sign. 

This month’s research roundup explores two key areas - ongoing studies concerning loss of taste and smell following COVID-19, along with new research into immune response that could help identify those who are more susceptible to severe and Long COVID in the very early stages of infection. Read on to find out more…

Loss of taste and smell and Long COVID

Anosmia, or loss of smell, has been a largely overlooked condition until COVID-19 placed it in the spotlight last year. Recent research carried out by the Monell Chemical Senses Centre in Philadelphia found that between 44% and 77% of COVID patients experienced complete loss of smell, usually accompanied by loss of taste, during the acute stage of their illness. An analysis conducted by the Global Consortium for Chemosensory Research last year showed that smell loss was the most reliable predictor of COVID-19.

Most COVID patients regain their senses of smell and taste within a few weeks. But the loss persists in a minority of patients, with no guarantee of when the senses will return. Danielle Reed, associate director at the Monell Chemical Senses Centre recently told the Guardian newspaper “What we know today is that after two months, about half the people who lost their sense of smell with COVID-19 still have impairments, and about 5-10% of those people have a serious impairment, so total or near-total loss of smell.” 

Anosmia can be a distressing and isolating condition. Some COVID-induced anosmia patients even experience a strange phenomenon called parosmia, where they detect unpleasant phantom odours, such as ammonia, burning plastic or dead fish.

Why does COVID-19 cause anosmia?

COVID-19’s influence on smell and taste resulted in a collaboration of international specialists led by Harvard Medical School. Authors of a research publication, yet to be peer reviewed, found that some COVID-19 sufferers may lose their sense of smell because the virus damages the olfactory receptor nerve endings or supporting olfactory cells within their nose that allow smell-detecting neurons to function. 

Researchers also speculated that infection of these supporting cells might lead to inflammation when the body tries to isolate and combat the virus, which can then impact smell function. 

Why are some people affected more than others?

Simon Gane, Consultant Rhinologist and ENT surgeon at City University of London and Jane Parker, Associate Professor of Flavour Chemistry at University of Reading explain their theory in an article published in The Conversation. They believe that some people suffer long-term smell loss due to their inflammatory response to COVID-19.

“Inflammation is the body’s response to damage and results in the release of chemicals that destroy the tissues involved,” they said. “When this inflammation is severe, other nearby cells start to be damaged or destroyed by this “splash damage”. We believe that accounts for the second stage, where the olfactory neurons are damaged.

“Recovery of smell is much slower because the olfactory neurons need time to regenerate from the supply of stem cells within the lining of the nose. Initial recovery is often associated with distortion of the sense of smell known as parosmia, where things don’t smell like they used to.” 

Viral load also appears to be a significant factor in the prevalence and timeline of anosmia. Rhinology Surgeon at University College London (UCL), Peter Andrews, and ENT specialist at UCL, Alfonso Luca Pendolino, led recently published research concerning 114 healthcare workers at hospitals in London and Padua, Italy who had tested positive for COVID-19. The research found that 70% had experienced smell and taste dysfunction. Of those surveyed, 60% continued to experience problems 52 days after infection.

What can be done to help with long-term anosmia?

Our smell function is extremely complex and further research is urgently needed, but specialists are hopeful that the brain will gradually re-learn to interpret signals as the olfactory lining starts to regenerate. Speaking to the Guardian newspaper in December 2020, Dr Peter Andrews said, “You can’t truly say someone’s lost their sense of smell until we’re 12-18 months down the line. This is a very plastic system which can heal itself, so it’s still very early days.”

Dr Andrews has relaunched an olfactory smell clinic at the Royal National ENT and Eastman Dental Hospitals to further investigate smell loss following COVID-19. He will examine biopsies of damaged olfactory cells to ascertain the potential for supporting cells to be transplanted. This would enable damaged cells to regenerate and reconnect to the central nervous system.

Smell training has been highlighted by the charity AbScent as a potential therapy. Anosmia patients take a few small sniffs from bottles of essential oils like cloves, eucalyptus or lemon and focus on the scent, even though they may not actually be able to smell it. Evidence suggests that smell training can be effective, but further research is needed as to whether it will work for COVID-19 smell loss. 

Anosmia due to COVID-19 has also led to trials in new therapies. At Mount Sinai Hospital in New York, Assistant Professor of Otolaryngology, Alfred Iloreta, is leading a trial treating patients with COVID-induced anosmia using omega-3 fatty acids in fish oil. He believes this could aid the healing process in the nasal cells damaged by the virus and the olfactory neurons.

Organisations currently raising awareness, helping sufferers and advocating for further research into COVID-induced anosmia include Monell Chemical Senses Centre, AbScent, Fifth Sense, Asomnia Awareness and the Global Consortium for Chemosensory Research.

Long COVID could be predicted in early stages of infection

This month we’re revisiting the body’s immune response in relation to Long COVID. New research, published by Cambridge University, believes clues as to why COVID affects some people more than others may lie in the way our immune system responds to the virus from the very early days of infection. 

The study recruited 207 people who had tested positive for COVID-19. Participants had varying responses to COVID-19 infection, and scientists monitored them for a period of 12 weeks after symptom onset. Scientists set out to explore two key areas; how effective were patients’ immune responses and the nature and extent of their inflammation. 

Researchers found that symptom patterns mapped to changes seen in patients’ blood samples. Those experiencing mild or asymptomatic COVID had a quick and robust adaptive early immune response. But, patients who were hospitalised by the virus showed profound abnormalities in immune cell numbers across a range of different cell types, and an abnormal inflammatory immune response in the very early days of infection. 

Scientists behind the study believe this shows that an atypical inflammatory component to the immune response is present around the time of COVID diagnosis in people who then progress to severe disease. Essentially, some people could be predisposed to severe COVID from the outset. The study notes, “Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset.”

Researchers found that viral load did not correlate with progression to inflammatory disease. However, once inflammatory disease was established, viral load was associated with subsequent severity.

Cambridge study may help to explain Long COVID

Some participants in the Cambridge University study had persistent abnormalities in their immune cells weeks or months after COVID-19 infection and scientists believe a change in the body’s inflammatory response may contribute to Long COVID. 

Talking about the research on the Naked Scientists podcast, Cambridge University Immunologist Professor Ken Smith said scientists are still following the patient cohort and would soon be collating 6-month data. 

Professor Smith commented, “There’s still evidence of marked immune abnormalities in many patients at 3 months, and those immune abnormalities can be seen in patients who’ve got better and gone home. And in a subset of patients, there’s evidence of persistent inflammation, which is of a slightly different nature to that which occurred earlier in the disease. Both of those things could underpin some of the clinical features of Long COVID.”

He continued, “The immune cell abnormalities are largely a reduction in a number of a lot of the different white cells in the blood, so called leukocytes. Many different leukocyte classes are profoundly reduced, and some of those cell numbers remain very low after three months, which could be consistent with, or could lead to, an inability of good immune responsiveness to other infections or secondary infections and that’s why we have to see if those [people] recover.”

Researchers speculate that Long COVID could be a sign of a diminished immune system struggling after COVID infection to combat other milder bacterial or viral infections. Study authors acknowledge that further research of patients with long-term immune abnormalities or persistent inflammation will enable more targeted treatment of Long COVID patients. 

Share your story

Long COVID is still shrouded in so many unknowns at this stage. Sufferers endure the frustrating reality of living with symptoms that have no guaranteed end-point. However, with growing numbers comes increased awareness and a louder call for research, alongside multidisciplinary clinical support and treatment.

We hope you’ve found our latest research roundup useful. What is your experience of Long COVID? We’d love to hear your thoughts. Please get in touch with the Sano team with your comments and feedback.

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