Dr Harsha Master, Dr Ashish Chaudhry, Dr Nicholas Gall, Dr Louise Newson, Dr Sarah Glynne, and Dr Paul Glynne present their experiences of diagnosing, managing, and referring patients with long COVID and associated conditions

Read this article to learn more about:

  • the definition, prevalence, and symptoms of long COVID
  • exclusion of alternative diagnoses, and identification of red-flag symptoms
  • the authors’ experiences of managing long COVID and its complications.

A two-page summary of key takeaways is also available to download at the bottom of this article.

Expert commentary by Professor Trisha Greenhalgh

Read this article online at: GinP.co.uk/456989.article

Reflect on your learning after reading this article with our reflective template at: GinP.co.uk/454221.article

Reflective templatecpd logo

Reflection is important for continuous learning and development, and a critical part of the revalidation process for healthcare professionals. Reflect on what you have learned after reading this article with our interactive template.

Currently, an estimated 2 million people in the UK are living with long COVID,1 and around 90 NHS long COVID clinics have been set up to support these patients.2 However, the management of patients with long COVID is complex, and requires coordination between primary, community, and secondary care. The slow emergence of high-quality evidence has resulted in a cautious approach to national guidance, and the optimum pathway design in long COVID clinics has yet to be determined. This has led to variation in the care and services for long COVID offered across the UK, with some areas not offering any post-COVID care at all.

Expert opinion may help to bridge this gap. Written by clinicians with lived experience of managing long COVID across these interfaces, this article aims to share our observations, and presents an overview of some of our findings in relation to the recognition, diagnosis, and management of long COVID and its associated conditions. We will discuss the emerging evidence on the condition, and provide helpful tips and resources that can be applied in any clinical setting. Practitioners should refer to the information and recommendations in individual summaries of product characteristics for all pharmacological therapies discussed in this article.

What we know so far

Definition, prevalence, and potential causes

Long COVID is defined as signs and symptoms consistent with COVID-19 that continue or develop for more than 12 weeks after acute COVID-19, and that are not explained by an alternative diagnosis.3 Up to one in three patients will go on to develop long COVID after contracting COVID-19.4  

The aetiology of long COVID is, as yet, unknown. Suggested causes include viral persistence,5 dysregulation of the immune system,5 autoantibodies,5,6 reactivation of latent viruses such as Epstein–Barr virus,7 aberrant mast cell activation,8,9 and microclots,10 all of which are plausible pathogeneses that may underlie the condition.

Presentation and course

Patients experiencing long COVID often present with complex symptoms across multiple organ systems (see Figure 1).3,11–14 Pre-existing illnesses may get worse, and conditions such as type 2 diabetes,15 hypertension16 and, in our experience, sleep apnoea are more commonly diagnosed after COVID-19. An increased incidence of autoimmune diseases, such as arthritis and vasculitis, has also been reported following COVID-19.17

Long COVID Figure 1

Figure 1: Some of the common symptoms of long COVID3,11–14

PoTS=postural orthostatic tachycardia syndrome; PEM=post-exertional malaise

© Dr Louise Newson, Dr Sarah Glynne, and Dr Paul Glynne. Creation by Newson Health Menopause Society and stock usage ©WinWin.artlab via Canva.com. Reproduced with permission.

The illness is characterised by an unpredictable, relapsing–remitting pattern with fluctuating symptoms (dubbed the ‘corona coaster’).3,18 Significant associated conditions can often appear weeks to months into the disease course.18 Without effective treatment, recovery is typically very slow; in fact, many patients remain symptomatic up to 2 years after the initial infection.1

Rehabilitation and recovery

Barriers to recovery from long COVID include stress,12 poor sleep,19 poor gut health,20 and menstrual hormone imbalance in women.13 Overexertion (both mental and physical) may cause an exacerbation of symptoms,12 termed the ‘boom-and-bust’ phenomenon (see the Holistic management of long COVID section below). We have observed that intercurrent infection can also trigger flares of long COVID symptoms.

A multidisciplinary approach that is tailored to the individual, involving medical assessment, investigations, treatment, and rehabilitation, is essential to facilitate a faster recovery.

Diagnosing long COVID

Long COVID is a diagnosis of exclusion—clinicians should consider and rule out other conditions,3,21 such as malignancy, ischaemic heart disease, infection, sleep apnoea, and perimenopause or menopause, and treat or refer via the usual pathways before considering referral to a long COVID clinic.

Clinical assessments that can be conducted to exclude alternative diagnoses are shown in Box 1.3,21

Box 1: Clinical assessments to rule out alternative diagnoses3,21

  • Take a medical history, and look for red flags
  • Measure the patient’s blood oxygen saturation at rest and on exertion (consider the 1-minute Sit-to-Stand Test)
  • Measure the patient’s blood pressure (lying and standing)
  • Take the patient’s pulse (lying and standing)
  • Take the patient’s temperature
  • Perform a physical examination according to the presenting symptoms
  • Order the following investigations:
    • blood tests
      • FBC, U&E, LFTs, CRP, TFTs, haematinics, and HbA1c; remember that D-dimer level is not always reliable for excluding thromboembolism
      • consider other tests, such as an early morning cortisol test, bone studies, a magnesium level test, and autoimmune tests, if indicated
      • consider BNP if the patient is short of breath and PoTS is suspected
      • consider oestradiol, testosterone, and SHBG in women (to calculate Free Androgen Index)
    • CXR
    • ECG
    • consider a home postural heart rate test/the NASA Lean Test to assess for orthostatic intolerance
    • in women, consider asking them to complete a menopause symptom questionnaire—an example is available on the balance website[A] and on the balance app.[B]

[A] balance website. Menopause symptom questionnaire. balance-menopause.com/uploads/2021/10/Menopause-Symptoms-Questionnaire-1.pdf

[B] balance website. balance app. www.balance-app.com

FBC=full blood count; U&E=urea and electrolytes; LFT=liver function test; CRP=C-reactive protein; TFT=thyroid function test; HbA1c =glycated haemoglobin; BNP=brain natriuretic peptide; PoTS=postural orthostatic tachycardia syndrome; SHBG=sex hormone binding globulin; CXR=chest X-ray; ECG=electrocardiogram; NASA=National Aeronautics and Space Administration

It is important to avoid the assumption that all symptoms are related to long COVID (termed ‘COVID bias’). Clinicians should consider the possibility of dual pathology, which may appear incidentally and may or may not be related to COVID-19. It is important to work through the usual symptoms and differentials while being aware of COVID bias.

Red flags

When reviewing patients with long COVID symptoms, it is vital to actively consider and exclude an acute pathology,3,21 which may not have presented in the acute phase of COVID-19. Clinicians should keep in mind that symptoms may be vague yet progressive in nature, and are at risk of being dismissed by both patients and clinicians as a result of COVID bias. Equally, patients may have multiple confounding symptoms, and may not prioritise a cardiac, respiratory, or neurological red-flag symptom when consulting a GP.

Red flags to look out for in patients with long COVID symptoms are listed in Box 2.3,4,11,21–23

Box 2: Red-flag symptoms3,4,11,21–23

  • Acute and progressive dyspnoea
  • Blood oxygen saturation <94% at rest
  • Desaturation on exertion
  • Deterioration in mental health
  • Exertional chest pain
  • Tachycardia at rest or on minimal exertion
  • Exertional syncope
  • Focal weakness
  • Expressive dysphasia
  • New-onset confusion.

Cardiovascular complications

Clinicians should remember to ask about exertional chest pain (even in younger patients), tachycardia at rest or on minimal exertion, and exertional syncope, because these symptoms may be ischaemic in nature.3,4,21 Early data also suggest that rates of myocarditis and pericarditis are increased in patients with long COVID;24 both of these conditions are recognised as presentations with post-viral or autoimmune aetiologies.25,26 In a large, retrospective cohort study of 718,365 patients with COVID-19, almost 5% developed myocarditis, and 1.5% developed pericarditis.27 Typical symptoms include pleuritic pain, which is improved by leaning forward and worse when lying flat, and arrythmia. If cardiovascular complications are suspected, electrocardiography (ECG) should be undertaken, followed by discussion with the local acute medical team, who may organise troponin testing, echocardiography, or even cardiac magnetic resonance imaging.21

Respiratory complications

Symptoms such as acute and progressive dyspnoeaa blood oxygen saturation lower than 94% at rest, and desaturation on exertion warrant discussion with the local acute medical team, and exclusion of pulmonary embolism (PE) and consideration of D-dimer testing or further imaging in a hospital setting.3,11,21,28 Factors that contribute to respiratory complications include an ongoing hypercoagulable state and pulmonary endothelial dysfunction, hospitalisation, and reduced mobility.29 If symptoms are suggestive of a PE, consider an acute referral, as D-dimer is not always a reliable indicator of PE after COVID-19.28 Anecdotally, we have seen that a small number of patients with a negative D-dimer test result can have positive imaging results. Once an acute pathology has been excluded, further investigations for ongoing breathlessness may include pulmonary function tests, brain natriuretic peptide testing, echocardiography, and high-resolution computed tomography.

Neurological complications

A variety of mechanisms, including virus-induced hypercoagulable states, direct central nervous system infection, and post-infectious immune-mediated phenomena are known to account for cerebrovascular accidents and transient ischaemic attacks, encephalopathy, and meningitis in patients with COVID-19.22 Clinicians should screen for expressive dysphasia, new-onset confusion, and focal weakness,11 and admit patients to an acute setting for assessment and neurological imaging as per local pathways.

Psychological complications

Finally, clinicians should consider the psychological distress that patients with long COVID experience as they develop new, unexplained, and disabling symptoms and potentially face a wait for care. This will have a significant impact on their psychological and social wellbeing. Primary care healthcare professionals should screen as normal for deteriorations in mental health and functioning,3,21 and for red flags such as an increased risk of self-harm, suicide, substance abuse, and psychosis.3

Long COVID clinics

Once alternative diagnoses have been excluded, patients should be referred to a long COVID clinic managed by a specialist multidisciplinary team. However, as yet, there is no recommended pathway for managing patients with long COVID. The Hertfordshire Community NHS Trust (HCT) Assessment and Rehabilitation Service was one of the first local pathways to be set up, and went live in August 2020. The pathway was established at pace amid considerable uncertainty; subsequently, it has developed and evolved in response to patient need.

Our experiences with the HCT Long COVID Assessment and Rehabilitation Service may serve as a guide for the development of similar services and are shown in Box 3.30  

Box 3: Learning points from the HCT Long COVID Assessment and Rehabilitation Service

  • Because long COVID is a diagnosis of exclusion, it is important that patients are first assessed by their own GP, undergo appropriate investigations if indicated, and have an acute pathology ruled out before being referred to a long COVID clinic
  • A jointly led service (between AHPs and GPs) that offers a combination of medical assessment and rehabilitation seems to work best in facilitating recovery
  • It is beneficial to appoint a specialised rehabilitation coordinator to triage patients at first entry—this ensures that an early holistic assessment of need is completed in order to organise a personalised package of care that includes medical review, if needed, and coordinated rehabilitation and support
  • It may be helpful to use a questionnaire such as the COVID-19 Yorkshire Rehabilitation Scale30 to document symptoms, symptom severity, and functional disability; it is also useful to do a comparison of a patient’s pre- and post-COVID functioning to assess the impact of long COVID on their daily life
  • Patients with complex symptoms should be discussed at a regular multidisciplinary team meeting; this will also enable shared clinical decision making, and allow for further learning and reflection
  • The multidisciplinary team should include, but not be limited to, a GPwSI in COVID-19, specialists in pulmonary rehabilitation and chronic fatigue, an occupational therapist, a physiotherapist, a speech and language therapist, an IAPT practitioner, and a psychologist
  • Ongoing unexplained symptoms warrant further review—a GPwSI in COVID-19 can offer a more detailed holistic medical assessment and coordinate a patient’s care; patients can also be referred for further investigations, such as CT scans, lung function tests, 24-hour cardiac monitoring, echocardiography, stress testing, MRI, and for further specialist review
  • As well as the physical implications, clinicians must consider the functionalemotionalpsychological, and financial impacts of COVID-19—clinics should work in an integrated way with secondary care, mental health services, social care, occupational health, and the voluntary sector
  • Early review by specialists in pulmonary rehabilitation can identify and treat disordered and dysfunctional breathing patterns—this can help to improve breathlessness, cough, fatigue, and anxiety
  • A slow-stream rehabilitation approach has been found to work best—patients often struggle with fatigue and brain fog, and can feel overwhelmed if referred to multiple teams at the same time
  • The cause of brain fog can be multifactorial, and performing cognitive tests too early is not always beneficial—fatigue services, occupational therapists, and psychologists are well placed to assess both cognition and fatigue after other causes (such as sleep apnoea and perimenopause or menopause) have been ruled out and associated conditions addressed
  • Exercise should be re-introduced cautiously, and only once an acute pathology has been ruled out—doing too much too soon can trigger a relapse.

HCT=Hertfordshire Community NHS Trust; AHP=allied health professional; GPwSI=GP with a special interest; IAPT=Improving Access to Psychological Therapies; CT=computed tomography; MRI=magnetic resonance imaging

Holistic management of long COVID

When planning the care of patients with long COVID, it is important to address key barriers to recovery, which include stress,12 overexertion,12 poor sleep,19 and poor gut health.20 In our experience, lifestyle measures such as minimising stresssleep optimisation, pacing, and improving diet are imperative to recovery, and can help to avoid an exacerbation of symptoms and post-exertional malaise.

Sleep optimisation

Sleep deficits can prolong recovery from COVID-19 and therefore must be addressed.12 We advise patients to pay careful attention to sleep hygiene by adopting consistent daily wake and sleep times, avoiding blue light from electronic screens for at least 1 hour before going to bed, and minimising alcohol and caffeine intake. Pharmacological intervention may also be required, to which the authors take a stepwise approach. The initial approach consists of a combination of 500 mg magnesium and 2–4 mg melatonin slow release once nightly (note: prescribing of melatonin is off-licence in individuals aged less than 55 years). If sleep disruption persists, a trial of low-dose amitriptyline (10–20 mg) once nightly could be considered.

Pacing and the boom-and-bust cycle

As a result of fluctuating symptoms, patients typically describe having ‘good and bad’ days. On ‘good’ days, more activity is often undertaken. However, this can then cause a ‘bad’ day, where symptoms worsen, and more rest is needed. This is known as the boom-and-bust cycle (see Figure 2).

Boom and bust cycle

Figure 2: The boom-and-bust cycle

© Dr Kim Morsley, Consultant Clinical Psychologist, and Sue Phelan, Clinical Specialist Occupational Therapist, Activate, Kingsway Health Centre, Stevenage. Reproduced with permission.

Pacing is an active self-management strategy whereby individuals, using knowledge of themselves and their condition, balance time spent on activity and rest in order to improve overall function and reduce the likelihood of exacerbating symptoms. Levels of activity can then be increased in a controlled way over time as stamina increases. Learning to pace can be challenging, and referral to specialist fatigue services is recommended if needed.

Encouraging patients to identify and address their unique triggers that cause a relapse, whether physical, mental, or emotional, can help to reduce the boom-and-bust phenomenon commonly seen after COVID-19 (see Figure 2).

In our experience, symptoms associated with a relapse may manifest immediately or after a delay of 24–48 hours, and can last days or months. A flexible, patient-centred, tailored return to work plan is therefore crucial for patients with long COVID.12

Relaxation techniques and complementary therapies

Although not evidence based, relaxation techniques such as meditation, mindfulness, yogic breathing, and Tai chi, and complementary therapies such as acupuncture, may reduce symptom severity and improve patients’ wellbeing.

Diet

Gastrointestinal (GI) symptoms and dysbiosis (an unhealthy gut microbiome) are common in patients with long COVID.12,20,31 Dysbiosis causes systemic inflammation, which may contribute to the pathogenesis of long COVID.32,33 There is emerging evidence that optimising gut health may reduce both GI and non-GI symptoms in patients with long COVID.32 Patients should be encouraged to eat a healthy, Mediterranean-style diet, consisting of up to 30 different plant-based ingredients per week, and to limit their intake of red meat, sugar, and processed foods.34–37  As in the Mediterranean diet,37 excessive alcohol and caffeine consumption should be avoided. Fermented foods34 and prebiotic and probiotic supplements32 may also be beneficial.

Management of associated conditions

Long COVID demonstrates significant overlap with other conditions, such as mast cell activation syndrome, dysautonomia, and the menopause. Management of these associated conditions is discussed in the following sections.

Mast cell activation syndrome

There is considerable overlap between some symptoms of long COVID and those of mast cell activation syndrome.8,9 Indeed, a significant reduction in symptom burden was evident in up to 72% of patients with long COVID treated for up to 16 weeks with a combination of H1 and H2 antihistamines38 —known mast cell stabilisers.8,9 The effectiveness of antihistamines for the treatment of long COVID is being further investigated in the STIMULATE-ICP trial at University College Hospital.39

Our standard antihistamine protocol is to recommend a therapeutic trial of the oral H1 antihistamine loratadine (10 mg twice daily), in combination with the H2 antihistamine famotidine (40 mg once daily), in all patients with long COVID.38 This treatment typically needs to be taken for a minimum of 3 months; if, however, after the first 6 weeks of therapy there is no patient-reported improvement in symptoms, clinicians could consider switching loratadine to the more potent H1 antihistamine fexofenadine (180 mg twice daily), in combination with an increased dose of famotidine (40 mg twice daily), with a clinical review scheduled after a further 6 weeks (note: prescribing of antihistamines is off-licence for the treatment of long COVID).38 Other useful strategies include the adoption of a low-histamine diet, and the addition of the mast cell stabiliser ketotifen, although specialist referral is recommended to guide further treatment.

Dysautonomia

In a preprint study analysing the results of an online survey of 2314 adults with long COVID, it was estimated that post-COVID autonomic dysfunction (dysautonomia) affects up to 67% of patients with long COVID.40 Some symptoms of long COVID may be related to virus- or immune-mediated dysfunction of the autonomic nervous system, resulting in transient or long-term orthostatic intolerance syndromes, such as postural orthostatic tachycardia syndrome (PoTS).23 Disruption of normal blood flow in PoTS can cause tachycardia, palpitations, breathlessness, and chest pain.41 Other symptoms can include dizziness, fainting, brain fog, fatigue, headache, and nausea.41 All of these symptoms are common in patients with long COVID.3

Once an acute pathology has been ruled out, the NASA Lean Test or the Active Stand Test can be used to diagnose PoTS.21,23,41 PoTS is characterised by a sustained increase in heart rate of 30 beats per minute or more when standing for 10 minutes (in the absence of orthostatic hypotension).41,42 Anecdotally, some patients with long COVID do not meet this criterion, but seem to be on the spectrum of PoTS, and respond to similar management strategies. The variability in diagnostic criteria are discussed in the 2020 Canadian Cardiovascular Society position statement on PoTS.43

Conservative measures include salt and water loading—increasing daily water consumption to around 3 l per day, and adding salt to food (around 10 g per day).23,42,43 If added dietary salt is poorly tolerated, then slow-release sodium tablets may provide an alternative—in our experience, a trial of two tablets three times a day for 30 days may be appropriate. Additional measures include wearing graduated compression stockings,23,41,42 as well as the lifestyle measures mentioned in the Holistic management of long COVID section. Patients should be encouraged to stay active, but to pace themselves.23,41,43 A gradual increase in the length and intensity of exercise is ideal.42  ‘Seated’ exercise (such as rowing or recumbent cycling) or swimming may be better tolerated.23,41–43 Gentle weight training may also help.41–43 Further useful information can be found on the following websites: www.potsuk.org and stopfainting.com.

There are no licensed medications for PoTS; however, consensus guidelines and other publications list a number of pharmacological treatment options that may provide effective symptomatic relief if conservative measures fail.41–43 These include beta-blockers, such as propranolol or bisoprolol.43 Beta-blockers may be initiated at the lowest dose (for example, 10–20 mg propranolol four times daily43) and increased slowly, but if they prove ineffective after a trial period of 4–6 weeks, they are unlikely to be helpful. Ivabradine, which slows the heart rate without affecting blood pressure, can also be considered.44,45 This may be started at 2.5 mg twice daily, and titrated up slowly to 7.5 mg twice daily or 5 mg three times a day, according to benefit.43–45 In our experience, blood pressure-supporting medication, such as fludrocortisone (200 mcg once daily) or midrodrine (2.5–10 mg three times a day), may also be helpful, but specialist referral may be required before commencement.

Menstrual changes and the menopause

Long COVID disproportionately affects women, and women aged 40–60 years are at highest risk of developing the condition.46,47 More than one-third of those who menstruate and contract long COVID report menstrual changes,12 and many of the symptoms of long COVID (fatigue, muscle aches, palpitations, brain fog, sleep disturbance, and headache) overlap with those of the perimenopause and menopause.3,13 In one study, 62% of women reported that their long COVID symptoms were worse just before their period, which is when oestrogen levels are at their lowest.13

COVID-19 is thought to affect the ovaries, causing inflammation and hormone imbalance.48,49 Ovarian capacity is reduced in perimenopausal women who contract COVID-19, and they are less likely to recover from the viral insult.48 Premature menopause, or premature ovarian insufficiency, affects one in 100 women under 40 years of age,50 so younger women may also present with symptoms of oestrogen deficiency. However, the degree to which hormone deficiency contributes to symptoms of long COVID varies between patients.

Despite mounting evidence that COVID-19 is causing a hormone imbalance that may be a barrier to recovery, many healthcare professionals remain unaware of the link. A survey by Newson Health Research and Education found that 84% of women with long COVID had never been asked about their periods by their doctor.13

Hormone replacement therapy (HRT) has a favourable risk–benefit profile for most women.51 A trial of HRT may be a useful diagnostic tool to differentiate between symptoms due to hormone deficiency and unrelated symptoms that require an alternative management strategy.49 HRT, including testosterone, can effectively treat symptoms of hormone deficiency, and may considerably improve quality of life for many women with long COVID (note: prescribing of HRT, including testosterone, is off-licence for the treatment of long COVID).49

HRT: easy prescribing guide has been written to support HRT prescribing in primary care, and is available to download from the Newson Health Menopause Society website (bit.ly/3yJjf9b).52 In our experience, body-identical HRT, with oestrogen as a patch, gel, or spray and micronised progesterone, is the optimal type of HRT. These types of HRT are not associated with risk of a clot or stroke.51 Testosterone can be prescribed as a gel or cream, and can often improve symptoms of low mood, reduced energy, brain fog, fatigue, muscle and joint pains, and low motivation.

It is essential that perimenopausal and menopausal women are not misdiagnosed with long COVID. Failure to recognise menopausal symptoms and initiate appropriate treatment may result in unnecessary debilitating symptoms and long-term health risks.49 Starting HRT within 10 years of the menopause, or under the age of 60 years, reduces future risk of many chronic conditions, including cardiovascular disease, dementia, osteoporosis, cancer, and depression.48,49,51

Summary

The sequelae of COVID-19 affect multiple body systems, can recede and recur, and may persist for prolonged periods, significantly impacting quality of life. Although clinicians must take care not to miss other acute pathologies by attributing every symptom to long COVID, effective management of the condition and its associated pathologies is essential to facilitate recovery. In the absence of a recommended pathway for long COVID, we hope that sharing our experiences of setting up a specialist clinic to deliver holistic care for people with long COVID will support the establishment and development of long COVID services, and improve care for people living with the condition.

Expert commentary

by Professor Trisha Greenhalgh, Professor of Primary Care Health Sciences, University of Oxford

‘Two years ago, long COVID was a new and strange disease of unknown cause, and many primary care clinicians felt underconfident to manage patients suspected of having this condition. While many unanswered questions remain, there are also now evidence-based pathways we can follow for assessing, investigating, and managing patients with long COVID. This article by an interdisciplinary team is an excellent starting point.’

Dr Harsha Master BSc MBBS MRCGP

GP Lead, COVID Assessment and Rehabilitation Service, Hertfordshire Community NHS Trust

Dr Ashish Chaudhry MBChB MRCP (UK) MRCGP PGDip FHEA

GP Partner and Trainer, Lower Broughton Health Centre, Salford; Clinical Lecturer, University of Manchester

Dr Nicholas Gall MSc MD FRCP

Consultant Cardiologist (Arrhythmias and Neuro-cardiology), King’s College Hospital; Honorary Senior Lecturer, King’s College London; Patron, PoTS UK; Medical Adviser, Syncope Trust And Reflex anoxic Seizures; Medical Adviser, Hypermobility Syndromes Association

Dr Louise Newson BSc (Hons) MBChB (Hons) MRCP FRCGP GP

Menopause Specialist; Chair of the Newson Health Menopause Society

Dr Sarah Glynne BSc (Hons) MBBS (Hons) MRCP MRCGP MSc

GP and menopause specialist; special interest in long COVID

Dr Paul Glynne PhD FRCP 

Consultant Physician, University College London Hospitals; Medical Director, The Physicians’ Clinic, London; special interest in long COVID

Conflicts of interest

Dr Louise Newson is the creator of the balance website and the founder of the balance app.

Note: At the time of publication (June 2022), some of the drugs discussed in this article did not have UK marketing authorisation for the indications discussed. Prescribers should refer to the individual summaries of product characteristics for further information and recommendations regarding the use of pharmacological therapies. For off-licence use of medicines, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices  for further information.

Useful resources

HCT=Hertfordshire Community NHS Trust; WHO=World Health Organization; SOM=The Society of Occupational Medicine; HRT=hormone-replacement therapy; PoTS=postural orthostatic tachycardia syndrome; ME=myalgic encephalomyelitis; RCOT=Royal College of Occupational Therapists

Reflective templatecpd logo

Reflection is important for continuous learning and development, and a critical part of the revalidation process for healthcare professionals. Reflect on what you have learned after reading this article with our interactive template.

References

  1. Office for National Statistics. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 1 June 2022. London: ONS, 2022. Available at: www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/1june2022
  2. NHS England website. Long COVID: the NHS plan for 2021/22www.england.nhs.uk/coronavirus/documents/long-covid-the-nhs-plan-for-2021-22/ (accessed 30 May 2022).
  3. NICE. COVID-19 rapid guideline: managing the long-term effects of COVID-19. NICE Guideline 188. NICE, 2020 (last updated 11 November 2021). Available at: www.nice.org.uk/ng188
  4. National Institute for Health and Care Research website. Up to one in three people who have had COVID-19 report long COVID symptoms. www.nihr.ac.uk/news/up-to-one-in-three-people-who-have-had-covid-19-report-long-covid-symptoms/27979 (accessed 26 May 2022).
  5. Brodin P, Casari G, Townsend L et al. Studying severe long COVID to understand post-infectious disorders beyond COVID-19. Nat Med 2022; 28: 879–882.
  6. Bhadelia N, Belkina A, Olson A et al. Distinct autoimmune antibody signatures between hospitalized acute COVID-19 patients, SARS-CoV-2 convalescent individuals, and unexposed pre-pandemic controls. medRxiv 2021. Preprint. doi: doi.org/10.1101/2021.01.21.21249176
  7. Su Y, Yuan D, Chen D et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell 2022; 185 (5): 881–895.
  8. Weinstock L, Brook J, Walters A et al. Mast cell activation symptoms are prevalent in long-COVID. Int J Infect Dis 2021; 112: 217–226.
  9. Afrin L, Weinstock L, Molderings G. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis 2020; 100: 327–332.
  10. Pretorius E, Vlok M, Venter C et al. Persistent clotting protein pathology in long COVID/post-acute sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol 2021; 20 (172).
  11. Chaudhry A, Master H. Top tips: managing long COVID. www.guidelinesinpractice.co.uk/infection/top-tips-managing-long-covid/455742.article (accessed 26 May 2022).
  12. Davis H, Assaf G, McCorkell L et al. Characterising long COVID in an international cohort: 7 months of symptoms and their impact. eClinical Medicine 2021; 38 (101019).
  13. Newson L, Lewis R, O’Hara M. Long covid and menopause—the important role of hormones in long covid must be considered. Maturitas 2021; 152: 74.
  14. Gall N, James S, Kavi L. Observational case series of postural tachycardia syndrome (PoTS) in post-COVID-19 patients. Br J Cardiology 2022; 29: 16–20.
  15. Rathmann W, Kuss O, Kostev K. Incidence of newly diagnosed diabetes after Covid-19. Diabetologia 2022; 65 (6): 949–954.
  16. Akpek M. Does COVID-19 cause hypertension? Angiology 2021; 33197211053903. Epub ahead of print.
  17. Gracia-Ramos A, Martin-Nares E, Hernández-Molina G. New onset of autoimmune diseases following COVID-19 diagnosis. Cells 2021; 10 (12): 3952.
  18. National Institute for Health and Care Research. Living with Covid19—second review. London: NIHR, 2021. Available at: evidence.nihr.ac.uk/themedreview/living-with-covid19-second-review/
  19. El Sayed S, Gomaa S, Shokry D et al. Sleep in post-COVID-19 recovery period and its impact on different domains of quality of life. Egypt J Neurol Psychiatry Neurosurg 2021; 57: 172.
  20. Yeoh Y, Zuo T, Lui G, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021; 70: 698–706.
  21. Nurek M, Rayner C, Freyer A et al. Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study. Br J Gen Pract 2021; 71 (712): e815–e825.
  22. Koralnik I, Tyler K. COVID-19: a global threat to the nervous system. Ann Neurol 2020; 88 (1): 1–11.
  23. Dani M, Dirksen A, Taraborrelli P et al. Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies. Clin Med (Lond) 2021; 21 (1): e63–e67.
  24. Puntmann V, Carerj M, Wieters I et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiology 2020; 5 (11): 1265–1273.
  25. Lampejo T, Durkin S, Bhatt N, Guttmann O. Acute myocarditis: aetiology, diagnosis and management. Clin Med 2021; 21 (5): e505–e510.
  26. Imazio M, Gaita F, LeWinter M. Evaluation and treatment of pericarditis: a systematic review. JAMA 2015; 314 (14): 1498–1506.
  27. Buckley B, Harrison S, Fazio-Eynullayeva E et al. Prevalence and clinical outcomes of myocarditis and pericarditis in 718,365 COVID-19 patients. Eur J Clin Invest 2021; 51 (11): e13679.
  28. Suh Y, Hong H, Ohana M et al. Pulmonary embolism and deep vein thrombosis in COVID-19: a systematic review and meta-analysis. Radiology 2020; 298: E70–E80.
  29. Vadukul P, Sharma D, Vincent P. Massive pulmonary embolism following recovery from COVID-19 infection: inflammation, thrombosis and the role of extended thromboprophylaxis. BMJ Case Rep 2020; 13: e238168.
  30. Barnoldswick Medical Centre. Covid 19 Yorkshire Rehab Screen (C19-YRS). Lancashire; Barnoldswick Medical Centre, 2021. Available at: www.barnoldswickmedicalcentre.co.uk/files/2021/09/C19-YRS-Covid-Rehab-screening-tool.pdf
  31. Liu Q, Mak J, Su Q et al. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut 2022; 71 (3): 544–552.
  32. Thomas R, Aldous J, Forsyth R et al. The influence of a blend of probiotic lactobacillus and prebiotic inulin on the duration and severity of symptoms among individuals with COVID-19. Infect Dis Diag Treat 2021; 5 (182).
  33. Thomas R, Williams M, Aldous J et al. A randomised, double-blind, placebo-controlled trial evaluating concentrated phytochemical-rich nutritional capsule in addition to a probiotic capsule on clinical outcomes among individuals with COVID-19—the UK Phyto-V Study. COVID 2022; 2 (4): 433–449.
  34. Spector T. Professor Tim Spector’s top 5 tips for a healthier gut microbiome. joinzoe.com/post/tim-spector-gut-tips (accessed 26 May 2022).
  35. Melbourne H. Nutrition and long COVID. Buckinghamshire: Buckinghamshire Healthcare NHS Trust, 2021. Available at: www.buckshealthcare.nhs.uk/pifs/nutrition-and-long-covid/
  36. The Association of UK Dietitians. Long covid and diet: food fact sheet. Birmingham: BDA, 2022. Available at: www.bda.uk.com/resource/long-covid-and-diet.html
  37. Willett W, Sacks F, Trichopoulou A et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr 1995; 61 (6 Suppl): 1402S–1406S.
  38. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med 2022; 70 (1): 61–67.
  39. University College London website. STIMULATE-ICP. www.ucl.ac.uk/health-informatics/research/stimulate-icp (accessed 26 May 2022).
  40. Larsen N, Stiles L, Shaik R et al. Characterization of autonomic symptom burden in long COVID: a global survey of 2,314 adults. medRxiv 2022. Preprint. doi: doi.org/10.1101/2022.04.25.22274300
  41. NHS website. Postural tachycardia syndrome (PoTS). www.nhs.uk/conditions/postural-tachycardia-syndrome/ (accessed 26 May 2022).
  42. Sheldon R, Grubb B, Olshansky B et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm 2015; 12 (6): e41–e63.
  43. Raj S, Guzman J, Harvey P et al. Canadian Cardiovascular Society position statement on postural orthostatic tachycardia syndrome (POTS) and related disorders of chronic orthostatic intolerance. Can J Cardiol 2020; 36 (3): 357–372.
  44. Tahir F, Bin Arif T, Majid Z et al. Ivabradine in postural orthostatic tachycardia syndrome: a review of the literature. Cureus 2020; 12 (4): e7868.
  45. Taub P, Zadourian A, Lo H et al. Randomized trial of ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2021; 77 (7): 861–871.
  46. Sudre C, Murray B, Varsavsky T et al. Attributes and predictors of long COVID. Nat Med 2021; 27: 626–631.
  47. Torjesen I. Covid-19: middle aged women face greater risk of debilitating long term symptoms. BMJ 2021; 372: n829.
  48. Newson L, Glynne S. Long COVID and female hormones. Warwickshire: Balance, 2022. Available at: www.newsonhealth.co.uk/uploads/2022/03/Long-COVID-and-female-hormones-factsheet.pdf
  49. Stewart S, Newson L, Briggs T et al. Long COVID risk—a signal to address sex hormones and women’s health. Lancet Reg Health Eur 2021; 11: 100242.
  50. NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015 (last updated December 2019). Available at: www.nice.org.uk/ng23
  51. Hamoda H, Panay N, Pedder H. The British Menopause Society and Women’s Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health 2020; 26 (4): 181–209.
  52. Newson Health Menopause Society. HRT: easy prescribing guide. Warwickshire: NHMS, 2022. Available at: www.nhmenopausesociety.org/resources/easy-hrt-prescribing-guide/

Credit:
Lead image: astrosystem/stock.adobe.com