Long COVID, its symptomatology and the role of family doctors in its management

Paul KM Poon 潘國明, Samuel YS Wong 黃仰山

HK Pract 2023;45:64-69

Summary

摘要

Introduction

It is still not completely clear why certain patients develop Long COVID while others recover quickly from the acute infection, without obvious sequelae. Although more severe acute infection is a risk for patients to develop Long COVID, some patients with mild or even asymptomatic infection have also suffered from Long COVID.¹ A meta-analysis² showed that female sex, poor pre-pandemic mental or general health, asthma, and obesity/overweight are also risk factors for developing Long COVID. Other risk factors include distinct gut microbiome³, hospitalisation, aged 35-69, living in a deprived area and working in healthcare, social care or education sector.^{1, 4-7} On the other hand, it is observed that Long COVID is less prevalent among fully vaccinated patients⁷ and the non-white population.8 The underlying pathogenesis of Long COVID is not fully known. Proposed mechanisms include chronic lowgrade inflammation⁹, immunothrombosis and endothelial dysfunction^10,11, autoimmune responses¹², and direct viral invasion of neurological tissues particularly to the autonomic nervous system.^6,13

Long COVID can be devastating and may lead to difficulties in activity of daily living, poor exercise tolerance, inability to work and study, loss of income, loss of social interaction, poor mental health, and decreased quality of life.^14,15 The disease course of different patients vary from constantly improving - to relapsing and remitting¹⁶, and are unpredictable. Studies showed that around two-thirds of COVID patients can be expected to recover by 12 weeks¹ but those who fail to get well at 12 weeks may reach a plateau with relapses or exacerbations triggered by physical or psychological stress.^7,9,17 Around one-third of symptomatic COVID patients seen in the outpatient settings reported not being able to take care of themselves and became dependent, to certain extent, on others at 3 months.¹⁸

Definitions

Long COVID generally refers to persistent or prolonged symptoms after acute SARS-CoV-2 infection and the symptoms are not explained by alternative diagnoses. There are multiple terms or definitions being adopted by different organisations including “post COVID-19 syndrome” adopted by the National Institute for Health and Care Excellence (NICE)¹⁹ and “post-COVID conditions” by the Centers for Disease Control and Prevention of the United States (US CDC).²⁰ The World Health Organization (WHO) has adopted “Post COVID-19 condition” in its International Classification of Diseases (ICD), which bears the following clinical case definition²¹:

Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others, which generally have an impact on everyday functioning. Symptoms may be new onset, following initial recovery from an acute COVID-19 episode, or persist from the initial illness. Symptoms may also fluctuate or relapse over time.

(A separate definition may be applicable for children.)

Symptomatology of Long COVID

A local study conducted in 2022 revealed that the most commonly reported Long COVID symptoms at six months were fatigue, poor memory, hair loss, anxiety and difficulty in sleeping.³ Another study in the United Kingdom showed that the most common ongoing symptoms at 4 months were fatigue, muscle ache, shortness of breath and headache.²² Meta-analyses showed that fatigue, dyspnoea, cough, sleep disturbances, anxiety, depression, cognitive impairment, and difficulty concentrating were the common symptoms.^23,24 Over 200 symptoms have been reported. Due to the limitations of space, only a selection of some specific of these will be discussed here in this article. In the following paragraphs, a number of common or special Long COVID symptoms will be discussed. For those readers who are interested in other possible symptoms, please refer to the comprehensive list in the reference section of this article for further reading.

(1) Fatigue

Fatigue is a subjective report of markedly reduced energy levels especially upon exercise or during daily activities, and the rate of energy depletion is not proportional to the level of exertion. Studies showed that over half of the hospitalised COVID patients experienced persistent fatigue at 2 months from onset of the first symptom.^25,26 Fatigue may cause marked impairment with work, study, exercise or even basic activities of daily living. Studies showed that fatigue also has detrimental effects on cognitive function, quality of life, social participation and employment.^27,28 Some patients can have their exercise tolerance significantly reduced and may develop a condition called post-exertional symptom exacerbation (PESE).

(2) PESE

PESE, also known as post-exertional malaise (PEM), is defined as worsening of symptoms (e.g., fatigue) after physical or mental exertion, typically 12-72 hours after exertion. The worsening of symptoms can last for days or rarely weeks. The triggering exertions can be of minimal intensity or the exertion levels were previously well tolerated by the patients.²⁹ PESE is an important factor to consider in the rehabilitation process of Long COVID patients especially with exercise prescriptions³⁰ as increased activity can be harmful if it leads to PESE.³¹ PESE is also an important cause of the unpredictable trajectory and episodic deteriorations of Long COVID symptoms and patients’ functional status.^16,32

(3) Orthostatic intolerance

Orthostatic intolerance manifests itself as fluctuations of heart rate and/or blood pressure particularly when the patient is in an upright position. There may also be excessive sweating, dizziness, or even syncope.³³ It is the results of autonomic dysregulation and overlaps to a certain extent with fatigue or PESE which are believed to have similar pathophysiological mechanisms.³⁰ For instance, PESP patients can also have serious chronotropic incompetence. On the other hand, some PESE patients may not have any orthostatic hemodynamic changes.

(4) Exertional dyspnoea and desaturation

Marked shortness of breath during exertion can be a sign of exertional desaturation. Exertional desaturation can be assessed by simple exercise testing (e.g., 1 minute sit to stand test³⁴), and a drop in oxygen saturation of 3–4% or to ≤ 94% on pulse oximetry is considered positive.³⁵ It is more commonly reported in COVID patients who were hospitalised during their acute infection.³⁶ Exertional desaturation requires further investigation to exclude new underlying pulmonary (e.g., pulmonary embolism) or cardiac (e.g., myocarditis) pathologies.³⁷ Exclusion of underlying pathologies is important for safe rehabilitation particularly prescription of exercise therapy.³⁴

(5) Brain fog

The term “brain fog” is often used to refer to the cognitive impairments after COVID infection including poor short-term memory, poor concentration, poor problem solving and executive functions. Studies showed that Long COVID is associated with impairments in alertness, concentration, memory, speech, and executive function.^38,39 A large cohort study in the United States showed that COVID patients who needed intensive care and had encephalopathy were more common to have substantial neurological and psychiatric morbidity at 6 months after the acute infection.²³ It is noteworthy that subjective cognitive concerns may be associated with emotional distress rather than objective cognitive dysfunctions in formal cognitive testing, and this should be borne in mind in managing these patients as emotional support may be what they actually need.³⁰

(6) Post-viral olfactory dysfunction (PVOD)

PVOD after COVID may be a partial or a total loss of smell (hyposmia or anosmia), distorted smell (parosmia), olfactory hallucination (phantosmia), or olfactory perseveration ("smell lock") that persist at 4 weeks after the acute infection.⁴⁰ PVOD can lead to the loss of enjoyment of food, reduced alertness to dangerous gas leak, and psychological distress.

Management of Long COVID and the role of family doctors

Currently, the mainstay of management of Long COVID is supportive and holistic care focusing on symptom control and, sometimes, treatment for treatable complications. While research on specific medications for Long COVID are ongoing, some common drugs can be used for symptom control e.g., paracetamol or nonsteroidal anti-inflammatory drugs for pain relief, and steroid spray for olfactory dysfunction. Preliminary data showed that COVID vaccines may also help lessen Long COVID symptoms but the improvement may be small and may conversely lead to a worsening in certain patients.^41,42 Besides, probiotics may be a potential and promising therapeutic option. Preliminary clinical studies including a randomised controlled trial in India showed that supplementation of Bacillus species with systemic enzymes improved both the physical and mental fatigue for COVID patients, and another randomised controlled trial in Mexico showed that probiotic formula of Lactiplantibacillus and Pediococcus species could shorten their clinical symptom duration.⁴³

Other than drugs, indeed most of the Long COVID symptoms (e.g.,cognitive impairment, olfactory dysfunction, fatigue, PESE, orthostatic intolerance, muscle and joint pain) can be effectively managed via a rehabilitative approach. For instance, rehabilitation management of cognitive impairment has been reported by patients to be helpful.³⁰ It may include cognitive exercises (e.g., task-specific training, cognitive/behavioural feedback, and caregiver-mediated exercises), self-management training, and adjustment (e.g., simplifying tasks into smaller components, use of assistive devices, environmental modifications, and recognising own limits).⁴⁴ Olfactory training, which has been shown to be effective in olfactory loss after infections of other coronaviruses⁴⁵, is another example. It is usually performed by repeated challenges to the nose with a number of known odorants (e.g. rose, clove, lemon) 2 times daily for 3 months.⁴⁵

Fatigue is also mainly managed by educating patients to work or function within their own energy limits including planning, pacing, building rest periods during activities.⁴⁶ Carefully titrated rehabilitation is another important intervention. Advice on pacing early in the rehabilitative process is reported by Long COVID patients to be useful.³⁰ It is important to forewarn patients of the unpredictable and fluctuating nature of the recovery course as well as the importance of sleep and rest.^16,32 Psychological support and cognitive behavioural therapy may also be considered in distressed patients.²⁹ Resumption of activities and exercises should be progressive with adaptations to the patients’ energy limits. Fixed incremental increase in activity level or graded exercise can be tried but they are not suitable for patients with PESE.²⁹ For patient with PESE, careful monitoring of symptoms to identify triggers, fareups, or relapses is important and an activity diary may be helpful. Similarly, exertional desaturation should also be ruled out before commencing exercise training which increase oxygen demand and can precipitate acute decompensation.³⁰ Identifying triggers and treat underlying new pathology together with pacing and modification to rehabilitation are needed to successfully manage patients with PESE or exertional desaturation.²⁹

Similarly, rehabilitative interventions are important in managing orthostatic intolerance. These include education to avoid symptom triggering factors like hot showers, straining, large meals, and standing up quickly from a supine/seated position. Environmental modifications like using a shower stool may be helpful. Skills or simple manoeuvres to relieve symptoms like tensing up their thighs or folding arms and legs can be taught to patients.47 If exercise is planned, training in a non-upright position e.g., using a recumbent bike, may be a good start for these patients.

Given the need for a holistic, coordinated and multidisciplinary care for Long COVID patients, family doctors can be the anchor for the overall management process. In addition, many patients may not be aware of the potential complications. Family physicians are the best healthcare professionals who can listen to the patients’ story, perform individualised assessments to outline the impact on the patients’ functioning, social life and mental health, build patients’ skills for rehabilitation and self-management, manage comorbidities, develop personalised rehabilitation plan, provide a continuity of care, refer patients to appropriate resources (e.g. physiotherapist, occupational therapists, etc.), and share patients’ worries linked to prognostic uncertainties.⁴⁸ Family doctors are also well-positioned to conduct a full history and physical examinations to identify alternative diagnosis or complications, and to screen and take action against red flags. Currently, there is no defined set of tests for all Long COVID patients because of the diversity in symptoms and severity. Family doctors should receive proper training in order to be able to identify red flags⁴⁹ (Table 1) and to provide counselling on life-threatening complications such as pulmonary embolism or myopericarditis.³⁰ Referral to secondary care or specialists should be made whenever warranted. (Table 2)

In addition, Long COVID may be under-reported or under-presented due to the lack of awareness of patients or the lack of training of healthcare professionals. PESE, exertional dysnoea and orthostatic intolerance may not be volunteered by patients and picked up by doctors without targeted and careful evaluations. Family doctors can actively look for these conditions that have marked implications on pacing for the rehabilitation process.

Way forward amid uncertainties

As of mid-November 2022, Hong Kong recorded 2 million COVID cases, and this number is believed to represent only a portion of the iceberg.⁵⁰ Over 90% of all the COVID cases recorded since the 5th local wave, these were believed to be caused by the omicron variants. Though evidence is still evolving, prevalence of Long COVID is reported to be similar for the omicron BA.² and the earlier dominant delta variant.⁷ A global systematic analysis estimates that around 10- 20% of COVID patients develop lingering symptoms²¹, however, there is still no official statistics on the number of Long COVID cases in Hong Kong.

Government-led designated Long COVID clinics have been set up in some countries including the United Kingdom, Germany, Belgium, Australia, Canada and Thailand.⁵¹ These clinics provide onestop services and aimed to improve coordination and increase efficiency for the needed multi-level and multidisciplinary Long COVID care. There are over 90 Long COVID clinics in England with general practitioners playing a key role with funding being allocated to the professional training of the primary care teams.⁵¹ In Hong Kong, Long COVID cases are mainly taken care of by the existing public healthcare system under different specialties but there are also some specific initiatives for Long COVID patients e.g. Special Chinese Medicine Outpatient Programme for COVID-19 infected persons of the Hospital Authority, a university-led one-stop COVID Recovery Clinic in a private hospital, a “3R Rehabilitation Programme” led by another local university. Since there is the need of coordinated multidisciplinary care pathways and agglomeration of resources on medical management, rehabilitative service, social service, psychological support, etc., a centralised government-led designated programme may be one of the best ways to tackle the Long COVID challenge on the healthcare system.

Besides, there is no gold standard with Long COVID management as uncertainties still prevail in many areas. For instance, there is no solid evidence for the rehabilitation management of cognitive impairment in Long COVID and current recommendations are based on studies among diverse patient populations with other causes of cognitive impairment.⁴⁴ Similarly, the current recommendations on managing PESE in Long COVID mainly follow guidelines on PESE in other health conditions⁵², and recommended interventions for orthostatic intolerance in Long COVID are mainly based on expert opinions only.³⁰ Despite the lack of a standardised protocol or guidelines, training of healthcare workers involving in Long COVID management is critical (e.g. in identifying red-flags). It has also been shown that the uncertainties and lack of training can precipitate healthcare workers burnout.⁵³ Strengthening healthcare manpower and increasing resource allocations to both relevant services and research are also imperative.

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