key: cord-0976336-rljbrven
authors: Patton, Lauren L.
title: Long-COVID and the practice of Oral Medicine
date: 2021-11-06
journal: Oral Surg Oral Med Oral Pathol Oral Radiol
DOI: 10.1016/j.oooo.2021.10.025
sha: 31c1e8135db97cf39a060b3f149b3e7488aece15
doc_id: 976336
cord_uid: rljbrven

nan

Once we are beyond the life and death concern, the scariest aspect to me of getting coronavirus disease 19 (COVID-19) is the prospect of long-term consequences that create disability and affect quality of life. In particular when facing the long-haul or long-COVID syndrome, there is possible prolonged duration of change in smell and taste, chronic fatigue, cognitive difficulties, and other unknown durable sequelae. Being surrounded by stories of taste changes, from my 13-year-old niece who reported her sudden taste loss to her mother that precipitated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, to my dental assistant who reported it was like a "taste switch" was turned off where her taste was fine at breakfast and acutely was altered by lunchtime, to my dental resident who initially experienced complete loss of taste and smell and still today, 11 months after acute COVID-19 recovery has altered taste/smell sensations described as an unusual, not particularly pleasant, singular taste/smell for all foods. Those in the practice of dentistry and particularly oral medicine may be sought out as consultants and care providers for a growing population with lingering effects of COVID-19 infection. Cases are now being reported of persisting parosmia and dysgeusia phenomenon, not fully recovered at 15 months after onset. 1 The terminology is still evolving to label those who have had COVID-19 and have persistent symptoms for longer than 3-4 weeks. Names for this condition were initially varied and termed post-acute COVID-19, post-acute sequelae of COVID-19 (PASC), chronic post-COVID, long-haul COVID and more recently shortened to long-COVID. Our ability to understand this condition or any new disease starts with consensus around a case definition. For long-COVID, the definition is still fluid and may change as does our understanding of this condition. The U.S. Centers for Disease Control and Prevention (CDC) 2 offers this current case definition: "Post-COVID conditions are a wide range of new, returning, or ongoing health 3 problems people can experience four or more weeks after first being infected with the virus that causes COVID-19. Even people who did not have COVID-19 symptoms in the days or weeks after they were infected can have post-COVID conditions. These conditions can present as different types and combinations of health problems for different lengths of time." The CDC post-COVID symptom list includes "change in smell or taste". 2 The U.S. government in July 2021, added long-COVID to the list of disabilities under the Americans with Disabilities Act, Section 504, and Section 1557 if a person with long-COVID condition's or any of its symptoms is a physical or mental impairment that substantially limits one of more major life activities. 3 The World Health Organization (WHO) 4 Our understanding of COVID-19 and its chronic debilitating sequelae is rapidly increasing with identification of previously unknown longer-term risks as time passes since the initial cases were identified. We still do not fully understand who might develop long-COVID, how long each of the symptoms last, and whether COVID-19 prompts the presentation of chronic diseases. With so many unknowns remaining to be addressed by scientific discovery, Dr. In a large pragmatic primary care study from the United Kingdom (U.K.) using patientreported outcomes and electronic health record data collected from August 2020 to January 2021, Jones and colleagues reported long-COVID (symptoms persisting beyond 4 weeks) to occur in about 10% of respondents who were self-diagnosed, clinician-diagnosed, and/or tested. 6 Risk predictors for long-COVID were age over 40 years, female sex, frailty, visit to hospital emergency department, and hospital admission for COVID symptoms. The impact of persistent 5 taste loss (reported by 44.5%) is a significant health burden, with almost every long-COVID sufferer (95.2%) reporting associated loss of appetite. 6 Appetite is essential to assure adequate nutritional intake. Taste is essential to preserve appetite and enjoyment of food and drink along with avoiding ingestion of spoiled or tainted unhealthy food items.

Age seems to matter with older patients being more susceptible to long-COVID. In a University of Washington longitudinal prospective cohort study, conducted between August and November 2020, of 177 mostly outpatients with mild or no presenting symptoms, 32.7% of outpatients and 31.3% of hospitalized patients reported at least one persistent symptom between 3 and 9 months after illness onset. 7 Persistent symptoms were slightly more common in older patients with reports by 26.6% aged 18-39 years, 30.1% aged 40-64 years, and 43.3% aged ≥65 years. Loss of sense of smell or taste and fatigue (both reported by 13.6% of patients) were the most common lingering symptoms. 7 We are learning that reports of anosmia and dysqeusia can persist for months after acute COVID resolves and serve as a marker of past infection. In a large retrospective Mass General Brigham electronic health record cohort study, involving over 96,000 patients tested between March 2020 and June 2021 for SARS-CoV-2 but not hospitalized, Estiri and coworkers identified that one of the 5 phenotypes documented with high confidence in the 3-6 month temporal window after PCR testing as indicating COVID infection was anosmia and dysgeusia. 8 In a study of 1031 Egyptian patients with COVID related olfactory and gustatory dysfunctions, Teaima and coworkers found that most improved in the first two weeks and by 6-month followup 66% had completely recovered, 22% partially recovered, but 12% had persistent dysfunction. 9 These dysfunctions were subclassified as: 50%, ageusia and anosmia; 23% hypogeusia and hyposmia in; 18%, anosmia alone; 18% phantosmia; and 28% parosmia. 9 6 Sufficient primary data has now been published to support a systematic review of short and long term rates of post-acute sequelae of SARS-CoV-2 infection giving us better estimates of disease burden. Groff and coworkers classified symptoms as short term (occurring 1 month after COVID-19 diagnosis or discharge), intermediate (2 to 5 months) and long term (6 months). 10 In their review of 57 studies published through March 2021 including over 250,000 COVID-19 survivors, researchers found that over half (54%) of survivors experienced at least one symptom 6 months after recovery with most common being pulmonary, neurologic (including anosmia and ageusia/dysgeusia), mental health, functional mobility impairments and general and constitutional symptoms of chest imaging abnormality, difficulty concentrating, general anxiety disorder, general functional impairments, and fatigue or muscle weakness. 10 Investigators included loss of taste/smell under the neurologic category of symptoms due to assumed mechanism of loss being a consequence of the effect of the virus on cranial nerve 1 (olfactory nerve) for smell and cranial nerves VII (facial), IX (glossopharyngeal nerve), and X (vagal nerve) for taste. Anosmia and dysgeusia both appear to have been reported on average, including first to third quartiles, with frequency between 8-18% in the included studies. 10 There is also an ongoing living systematic review protocol out of the U.K. to keep scientists, patients, and policy makers updated on this rapidly developing condition. 11 Overcoming vaccine hesitancy is a first step in preventing becoming a long-COVID sufferer. The importance of vaccination for decreasing risk of long-COVID was emphasized recently by a report of a large U.K. adult prospective, community-based, nested, case-control study of COVID symptoms, test positivity, and vaccination status self-reported by over 1.5 7 million users in a mobile phone study app between March 2020 and July 2021. 12 Antonelli and coworkers found that among those with COVID infection, the odds of adults having symptom duration of 28 or more days was reduced by almost half among those who had received two vaccine doses compared to unvaccinated adults. 12 Oral medicine providers engaged in promoting and/or administering COVID-19 vaccinations can help in this disease prevention effort.

In general, research to date has failed to identify detailed causes of long-COVID symptoms, aspects that impact their severity, or how long they will last and what is the potential recovery trajectory. It is essential that we identify the mechanisms underlying the diverse symptoms that can affect survivors so that the long-term health consequences of COVID-19 can be prevented and/or treated effectively. Several hypotheses around cause of COVID-related anosmia have been proposed, with the angiotensin-converting enzyme 2 (ACE-2) being a major player. 13 These include olfactory cleft obstruction, local inflammation in the olfactory epithelium Can we develop and implement therapeutic approaches to improve or reset long-COVID taste/smell loss or dysfunction? Current treatment options being explored for anosmia include olfactory training exercises, intranasal or oral corticosteroids, and intranasal sodium citrate, with several promising novel therapeutic options including tissue engineering/gene therapy and stem cell therapy under development. 13 Other therapeutics suggested for management of smell and taste loss include neuroprotective (Omega-3), anti-inflammatory and depolarizing agents including corticosteroids (intranasal fluticasone; oral triamcinolone paste), phosphodiesterase inhibitors (pentoxifylline), and intranasal insulin. 14 Chabot and Huntwork propose ingestion of one 1000mg dose of a (curcumin) turmeric supplement, thought to be beneficial for various oncologic and autoimmune ailments, may help restore long-COVID related taste and smell. 15 As Oral Medicine specialists conducting research in other medically complex patient cohorts, such as head and neck cancer patients who experience qualitative changes in taste/smell as a result of chemotherapy and radiation therapy, we will need to account for possible long-COVID dysgeusia/anosmia confounding our qualitative outcomes. Unfortunately, we currently lack robust validated objective biomarkers and have limited tools to aid in diagnosis and to quantifiably measure the state and quality of anosmia and dysgeusia specific to long-COVID in clinical and research settings. More objective chemosensory (olfactory and taste) function testing 9 tools are needed to provide more details about the changes of parosmia and dysgeusia throughout both the acute COVID experience and long-COVID periods of recovery.

With 244 million global (45 million in the U.S.) COVID-19 infections reported to date by WHO 16 and an estimated 8-18% experiencing long-COVID related prolonged taste/smell dysfunction, 10 we can anticipate having more than 20-44 million survivors globally (3.6-8.1 million in the U.S.) potentially seeking help to manage their possibly chronic taste/smell sensory disability. Has long-COVID created a gap in care that Oral Medicine specialists can help fill?

Persistent chemosensory dysfunction in a young patient with mild COVID-19 with partial recovery 15 months after the onset

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Office of Civil Rights. Guidance on "Long COVID" as a Disability Under the ADA, Section 504, and Section 1557. Content last reviewed

World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus

National Institutes of Health. NIH launches new initiative to study "Long COVID

Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients

Sequelae in adults at 6 months after COVID-19 infection

Evolving phenotypes of non-hospitalized patients that indicate long COVID

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review

What are the long-term symptoms and complications of COVID-19: a protocol for a living systematic review

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study

Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments

Potential pharmacologic treatments for COVID-19 smell and taste loss: A comprehensive review

Turmeric as a Possible Treatment for COVID-19-Induced Anosmia and Ageusia

World Health Organization. WHO Coronavirus (COVID-19) Dashboard