This Guidelines summary of Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study covers key recommendations to provide a rapid expert guide for GPs and clinical services in the recognition, diagnosis, and management of post-COVID-19 syndrome, also known as long COVID.
The Delphi method was used to derive 35 clear and practical recommendations by UK clinicians with an interest in and lived experience of long COVID.
For further information, refer to the full guideline.
View this summary online at guidelines.co.uk/456430.article
- COVID-19 is a new condition with increasing evidence of serious long-term sequelae, including cardiac, respiratory, and renal disease, new-onset diabetes, and excess deaths reported
- It cannot, therefore, be assumed that patients are suffering from self-limiting postviral fatigue and that rehabilitation is sufficient. However, input from expert physiotherapists and occupational therapists who are familiar with the condition is an important aspect of caring for patients with long COVID
- Patients require a holistic clinical approach that prioritises investigation of potential physical pathology
- The lead clinician should be a doctor, ‘well versed in multisystem disorders’, working across disciplines, and who is able to refer patients to specialists.
Box 1: Known examples of conditions associated with long COVID
- Myocarditis or pericarditis
- Microvascular angina
- Cardiac arrhythmias, including inappropriate sinus tachycardia, atrial flutter, atrial fibrillation, and high burden of ventricular ectopics
- Dysautonomia, including postural (orthostatic) tachycardia syndrome (PoTS)
- Mast cell activation, including urticaria, angioedema, and histamine intolerance
- Interstitial lung disease
- Thromboembolic disease (for example, pulmonary emboli, microthrombi, or cerebral venous thrombosis)
- Myelopathy, neuropathy, and neurocognitive disorders
- Renal impairment
- New-onset diabetes and thyroiditis
- Hepatitis and abnormal liver enzymes
- Persistent gastrointestinal disturbance, including heartburn, diarrhoea, and loss of appetite
- New-onset allergies and anaphylaxis
- Long COVID is not a primary mental health problem, but mental health specialists such as neuropsychiatrists can offer a supporting role to the multidisciplinary team. Psychological aspects of disease should be managed as part of the recovery process, but not seen as the primary treatment focus
- No discrimination should exist in the treatment of patients with pre-existing mental health difficulties with regard to equal access to care for their long COVID and appropriate investigations for organ damage
- Regarding children, a consultant paediatrician should lead the service. NICE guidelines recommend considering referral from 4 weeks for specialist advice for children with ongoing symptomatic COVID- 19 or long COVID.
Box 2: Recommendations relating to clinic organisation
- Consider long COVID in patients with a clinical diagnosis of COVID-19, as per World Health Organization (WHO) criteria, or test positive history with new or fluctuating symptoms, including but not limited to: breathlessness; chest pain; palpitations; inappropriate tachycardia; wheeze; stridor; urticaria; abdominal pain; diarrhoea; arthralgia; neuralgia; dysphonia; fatigue including neurocognitive fatigue; cognitive impairment; prolonged pyrexia; and neuropathy occurring beyond 4 weeks of initial COVID-19
- Multi-specialty long COVID clinics should be led by a doctor with cross-specialty knowledge and experience of managing this condition
- Consider individualised investigations, management, and rehabilitation planning via a multi-specialty long COVID assessment service as local services allow. Prioritise physician-led medical assessments and diagnostics initially, and consider allied health professionals including physiotherapy and occupational therapist input as adjuncts
- It is inappropriate for long COVID clinics to be led by mental health specialists, for example, improved access to psychological therapy, clinical, or health psychologist. They may be useful in supporting the multi-specialty team but do not have the expertise to investigate and manage potential organ damage
- All under-18-year-olds need access to similar services run by paediatric specialists with knowledge of how presentations and treatments differ for adults, and with close liaison with school
- Patients with comorbid mental health difficulties should have equal access to medical care as a patient without mental health difficulties, and should not be triaged away from services.
Diagnosis of underlying disorders
- At present, there is a considerable risk to patient safety if appropriate investigation of common symptoms of long COVID (such as chest pain, breathlessness, palpitations, abdominal pain, or fatigue) that have wide differential diagnoses is not undertaken
- Serious conditions, related to SARS-CoV-2 infection or not, must be adequately excluded, and investigations should be appropriately guided by the history.
- Long COVID-specific examination (for example, the NASA Lean Test for postural tachycardia syndrome [PoTS]) or tests such as electrocardiogram (ECG) are best conducted in person, and chest X-ray (CXR) may be appropriate
- CXR may exclude relevant pathology such as tuberculosis, but is less relevant in investigating cardiac, pulmonary vascular, or autonomic causes for breathlessness where computed tomography or ventilation/perfusion scans are more likely to be indicated
- Spirometry with beta-agonist reversibility could be used to diagnose airway hyperreactivity
- Studies on venous thromboembolic disease are limited to patients with acute COVID-19, severe disease, or based on expert opinion, but are an important diagnosis to consider
- Oxygen desaturation on exertion occurs in both acute and long COVID, and should form part of the baseline assessment. The only thresholds for defining levels of concern for hypoxaemia and desaturation with exercise related to acute COVID-19, and no agreed thresholds are available in long COVID
- Assessments such as 1-minute sit-to-stand tests and 6-minute walk tests do or should form part of the assessment in community or specialist clinics. The exertional test chosen should take account of any pre-COVID-19 limitations, and should include heart rate, as this may help to assess autonomic function.
- Referral for more detailed assessment is required in the following scenarios:
- desaturation with or without overt/reported dyspnoea
- nocturnal desaturation
- extreme fatigue
- behavioural change in those who struggle with verbal communication
- patient reports significant post-exercise malaise after such testing (lasting beyond the next day)
- severe tachycardia
- postural blood pressure drop.
- There is increasing evidence of cardiovascular complications with COVID-19. Patients with long COVID (of all ages) have been diagnosed with arrhythmias, autonomic dysfunction, myocarditis, pericarditis, and microvascular ischaemia
- Autonomic dysfunction, especially manifesting as PoTS, occurs commonly post COVID-19. There is a need to consider a differential for tachycardia and palpitations that, in long COVID, includes pulmonary embolus, cardiac, and respiratory causes. Autonomic dysfunction should also be suspected in patients with light-headedness, chest pain, and nausea, and the association of autonomic dysfunction with mast cell disorders considered.
- Neurocognitive testing is a particularly scarce resource, and neurology review and brain MRI may be more helpful early in the illness. The benefits of testing would support the need for rehabilitation from occupational therapy or a neuropsychologist
- NICE guidelines on long COVID advise considering neuropsychometric testing after 6 months if no improvement/worsening of cognitive function, as many will resolve
- Clinicians should include long COVID in a differential diagnosis of arthritis once other known autoimmune causes have been excluded.
Box 3: Recommendations relating to diagnosis of underlying disorders
- In someone with long COVID, symptoms of possible non-COVID-19-related issues should be investigated and referred as per local guidelines. Long COVID alone is not a sufficient diagnosis unless other causes have been excluded
- Carry out a face-to-face assessment including a thorough history and examination, consider other non-COVID-19-related diagnoses, and measure full blood count, renal function, C-reactive protein, liver function test, thyroid function, haemoglobin A1c, vitamin D, magnesium,[A] B12, folate, ferritin, and bone studies.
- In those with respiratory symptoms, consider CXR at an early stage. Be aware that a normal appearance does not exclude respiratory pathology
- Be aware that simple spirometry may be normal, but patients may have diffusion defects indicative of scarring, chronic pulmonary embolisms, or microthrombi. Consider referral to respiratory for full lung function testing
- Measure oxygen saturation at rest and after an age-appropriate brief exercise test in people with breathlessness, and refer for investigation if hypoxaemic or if any desaturation on exercise.
- Consider the possibility of a cardiac cause of breathlessness
- Be aware that a normal D-dimer may not exclude thromboembolism, especially in a chronic setting, and referral for investigation is therefore indicated if there is a clinical suspicion of pulmonary emboli. Additionally, be mindful that thromboembolism may occur at any stage during the disease course
- In patients with inappropriate tachycardia and/or chest pain, carry out ECG, troponin, Holter monitoring, and echocardiography. Be aware that myocarditis and pericarditis cannot be excluded on echocardiography alone
- In patients with chest pain, consider a referral to cardiology, as cardiac magnetic resonance imaging may be indicated in a normal echo to rule out myopericarditis and microvascular angina
- In patients with palpitations and/or tachycardia, consider autonomic dysfunction.
- In patients with urticaria, conjunctivitis, wheeze, inappropriate tachycardia, palpitations, shortness of breath, heartburn, abdominal cramps or bloating, diarrhoea, sleep disturbance, or neurocognitive fatigue, consider mast cell disorder
- In patients with cognitive difficulties sufficient to interfere with work or social functioning, consider neurocognitive assessment
- In patients with joint swelling and arthralgia, consider a diagnosis of reactive arthritis or new connective tissue disease and investigate and refer as appropriate.
[A] Magnesium level may not be available in general practice.
- Long COVID, like all long-term conditions, has an impact on many aspects of life and is best managed holistically with physical, psychological, and social factors addressed. Prolonged illness following SARS-CoV-2 infection is characterised by the development of new symptoms at different timepoints. Clinicians need to provide patient ‘safety-netting’ advice and guidance on expected patterns of illness
- The experience of many patients is of post-exertional symptom relapse. Physical or cognitive workload beyond the patient’s ‘energy envelope’ may cause an exacerbation of symptoms including fatigue, fever, myalgia, and breathlessness
- Exacerbations may manifest immediately or after a delay of 24–48 hours and may last days or months. As the threshold for this effect varies not only by patient but over time, pacing needs to be flexible and careful
- Doctors play a key role in supporting patients through the complexity of specialist investigations and differential diagnoses, and considering symptomatic treatments
- Patients should be made aware of research studies: participation could add meaning to what is often a very negative experience.
- Occupational health service referrals and medical reports supporting the return-to-work process are needed
- The relapsing–remitting nature of the illness needs to be emphasised, as employer pressure may result in patients returning to work too soon. The onus is on the doctor with current clinical responsibility for the patient to complete the fit note
- The content of the fit note should be agreed upon between the patient and doctor, including a ‘medically-recognised diagnosis’. For NHS staff to receive ‘COVID pay’ during absence, the fit note must mention COVID
- The ability to return to work after illness is a marker of recovery and clinicians must, therefore, record work status in the clinical notes in situations of chronic ill health
- From a public health perspective, counting days lost to sickness and lost income on account of long COVID is essential.
Box 4: Recommendations relating to management: general approach
- For patients with fatigue and worsening symptoms hours to days following an activity, emphasise the importance of an initial phase of convalescence followed by careful pacing and rest
- Support patients in shifting their mental timeline of recovery to reflect the likely prolonged course, with a possibly long phased return to work
- Further support patients with signposting to patient resources. Applicable resources may include: management of post-exertional symptom exacerbation; activity pacing; acupuncture; and diagnosis-specific management as relevant
- Provide patients with signposting to social prescribing, sickness certification, and financial advice. Discuss with the patient whether sickness certification will state long COVID as diagnosis
- Clinicians should ensure that the occupational status of patients with long COVID is recorded (in/out of work, part-/full-time, student)
- Follow patients up regularly to monitor progress from a full biopsychosocial and occupational perspective
- Encourage reporting of new symptoms (expected) and expectation of waxing–waning course
- Consider contributing patient data to research on long COVID, using the WHO case report form or similar.
Management: specific conditions
- Ongoing exertional chest pain may warrant referral to a rapid access chest pain clinic and/or cardiac magnetic resonance imaging
- In patients diagnosed with myocarditis, exercise to 60% maximum heart rate can be advised, but patients need to work out their own limits, which may be lower than this. In some cases of myocarditis or pericarditis, there is a difficulty in managing tachycardia, and pharmacological approaches are needed, such as beta-blockers or ivabradine. As colchicine and antianginals may also be helpful, advice from a long COVID assessment clinic needs to be sought
- PoTS (and other dysautonomic symptoms such as breathlessness, orthostatic intolerance, dizziness, and tremor) is an unfamiliar diagnosis for many clinicians, but seems to affect a significant subgroup of patients with long COVID
- PoTS treatment can start with fluids, compression, and lifestyle adaptations (for which specific patient support materials are available), but may need to escalate to medication if symptoms are not improved. Midodrine may be helpful, although this is only available following secondary care initiating the prescription in many parts of the UK
- Similarly to treating urticaria, mast cell features require two- to four-fold larger doses of antihistamines to suppress them. Dermatologists and GPs with an interest in mast cell disorders have experience in counselling patients about such off-label use, and an individual therapeutic trial is simple to arrange
- Some patients exhibit sensitivity to histamine-rich foods and prominent gastrointestinal symptoms (bloating, cramping pain, diarrhoea, acid reflux). These, and other known triggers of mast cell activation, should be avoided; the aim is to switch off the immune overreaction
- The term ‘breathing pattern disorder’ was used in the original guidance to describe the subjective experience of patients that is not ‘breathlessness’ in the strict sense of the word. Its aetiology is unknown but may represent a disorder of central breathing control. Meditation/mindfulness is promoted in the NHS as an effective therapy for anxiety and the sensation of breathlessness
- Having a mental health disorder should not preclude investigation of any organic disease, and unexplained symptoms, signs, and neuropsychiatric features should always prompt exclusion of organic pathology in the first place. Addressing epistemic injustice issues in the investigation and management of long COVID should be a priority for local services
- Patients with long COVID commonly refer to taking ‘the stack’ or ‘the supplement stack’, which includes high-dose vitamin C and D, niacin (nicotinic acid), quercetin, zinc, selenium, and sometimes also magnesium. Examples of noteworthy interactions with supplements include: niacin causing an increased risk of bleeding events when combined with selective serotonin reuptake inhibitors or nonsteroidal anti-inflammatory drugs, increased risk of rhabdomyolysis together with statins, and quercetin causing inhibition and induction of various human cytochrome P450 enzymes.
Box 5: Recommendations relating to management: specific conditions
- Patients with cardiac symptoms should be advised to limit their heart rate to 60% of maximum (usually around 100–110 beats per minute), and investigated with at least ECG and echocardiogram before taking up exercise. Supervised exercise testing should be considered for this patient group; they may have perimyocarditis, and exercise carries risk of arrhythmia and worsening cardiac function
- For autonomic dysfunction including PoTs, consider first increased fluids, salts, compression hosiery, and specific rehabilitation
- If PoTS, and no or inadequate response to non-pharmacological therapy, consider beta-blocker, ivabradine, or fludrocortisone (with blood pressure and response monitoring)
- In patients with possible mast cell disorder, consider a 1-month trial of initial medical treatment and dietary advice. Higher than standard dose of antihistamines are commonly used for this indication. If partial effect, consider adding second-level treatment such as montelukast, as well as referral to allergy or immunology specialists
- Be aware that adverse drug reactions are more common in patients with mast cell disorder, for example, to beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs, codeine, morphine, or buprenorphine
- For breathing pattern disorder, consider specialist physiotherapy and/or using alternative therapies such as pranayama breathing and meditation
- In patients expressing distress, significant low mood, anxiety, or symptoms of post-traumatic stress disorder, consider mental health assessment
- Over-the-counter supplementation is common, including vitamin C, D, niacin (nicotinic acid), and quercetin. Be aware of significant drug interactions, such as with niacin or quercetin.
Nurek M, Rayner C, Freyer A, Taylor S, Järte L, MacDermott N, and Delaney BC on behalf of the Delphi panellists. Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study. BJGP, 2021. Available at: bjgp.org/content/early/2021/10/04/BJGP.2021.0265
Published date: 04 October 2021.
Lead image: zakalinka/stock.adobe.com