Expert Recommendations on the Diagnosis and Management of long COVID

"It is estimated that one million people in the UK are currently living with long COVID, and with the total number of UK COVID-19 cases nearing 8 million, the further implications of long COVID for patients and healthcare services is uncertain.

As the illness is commonly unpredictable, with a relapsing-remitting pattern and associated conditions often appearing weeks to months into the disease course, clinicians will need to have a high index of suspicion and a low threshold for referral to secondary care specialists or long COVID clinics".

This month the work of the Delphi panellists was printed in the British Journal of General Practitioners.

Nurek M, Rayner C, Freyer A, Taylor S, Järte L, MacDermott N, Delaney BC; the Delphi panellists. Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study. Br J Gen Pract. 2021 Oct 5. doi: 10.3399/BJGP.2021.0265.

In health sciences, the Delphi technique is primarily used by researchers when the available knowledge is incomplete or subject to uncertainty and other methods that provide higher levels of evidence cannot be used. It needed to be used for Long Covid as this is a new disease with no previous research available. The aim of a Delphi Study is to collect expert-based judgments and to use them to identify consensus for symptoms, diagnosis and possible treatments. For this study the team of experts were doctors living, or treating those, with long Covid. I previously wrote about this in April 2021 but with the updated NICE guidelines on Long Covid on their way (don't hold your breath) medical reporters are describing this particular study as recommendations for long Covid that "go further than NICE guidance".

Why did they do it?

In the absence of research into therapies and care pathways for long COVID, guidance based on 'emerging experience' is needed.

What was their aim?

To provide a rapid expert guide for GPs and long COVID clinical services where there remains limited evidence on optimal investigation and treatment of this new condition.

What did they do?

A Delphi study was conducted with a panel of primary and secondary care doctors.

How did they do it?

Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of 'strongly agree', 'agree', or 'neither agree nor disagree' from 90% or more of responders were taken as showing consensus.

Thus a group of 33 clinicians representing 14 specialties came together and have produced 35 consensus-based recommendations on the recognition, investigation and management of long COVID.

What are their recommendations?

Diagnosis of long Covid

The panel advises that a diagnosis of long COVID should be considered in patients with a clinical diagnosis of COVID-19 or who have tested positive for COVID-19 and present 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, neurocognitive fatigue, cognitive impairment, prolonged pyrexia and neuropathy occurring beyond four weeks of initial COVID-19.

Outcomes of long Covid

As knowledge about long COVID is still evolving, associated conditions have yet to be fully delineated, but some accepted sequelae include:

  • 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 (e.g., 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.

  • Dysphonia.

13 recommendations to guide the diagnosis of long COVID-related conditions

  1. 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.

  2. 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, B12, folate, ferritin and bone.

  3. In those with respiratory symptoms, consider chest X-ray at an early stage. Be aware that a normal appearance does not exclude respiratory pathology.

  4. Be aware that simple spirometry may be normal but patients may have diffusion defects indicative of scarring, chronic pulmonary embolisms or microthrombi. Consider referral for full lung function testing.

  5. Measure oxygen saturation at rest and after an age-appropriate brief exercise test in people with breathlessness and refer for investigation if there is hypoxaemic or if there is any desaturation on exercise.

  6. Consider the possibility of a cardiac cause of breathlessness.

  7. Be aware that a normal D-dimer may not exclude thromboembolism, especially in a chronic setting. Referral for investigation is indicated if there is a clinical suspicion of pulmonary emboli. Thromboembolism may occur at any stage during the disease course.

  8. In patients with inappropriate tachycardia and/or chest pain, carry out electrocardiogram (ECG), troponin, Holter monitoring and echocardiography. Be aware that myocarditis and pericarditis cannot be excluded on echocardiography alone.

  9. In patients with chest pain, cardiac magnetic resonance imaging may be indicated in a normal echo to rule out myopericarditis and microvascular angina.

  10. In patients with palpitations and/or tachycardia, consider autonomic dysfunction.

  11. 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.

  12. Consider a neurocognitive assessment in patients with cognitive difficulties sufficient to interfere with work or social functioning.

  13. In patients with joint swelling and arthralgia, consider a diagnosis of reactive arthritis or new connective tissue disease and investigate and refer as appropriate.

Recommendations on the management of long COVID conditions

  1. Patients with cardiac symptoms should limit their heart rate to 60 per cent of maximum (usually around 100-110 beats per minute) and should undergo at least ECG and echocardiogram before taking up exercise. Supervised exercise testing should be considered as these patient may have perimyocarditis and exercise carries a risk of arrhythmia and worsening cardiac function.

  2. For autonomic dysfunction including PoTs, consider increased fluids, salts, compression hosiery and specific rehabilitation.

  3. In patients with PoTS who experience no or inadequate response to non-pharmacological therapy, consider a beta-blocker, ivabradine or fludrocortisone, with blood pressure and response monitoring.

  4. In patients with possible mast cell disorder, consider a one-month trial of initial medical treatment and dietary advice. Higher than normal doses of antihistamines are commonly used for this indication. If these only achieve a partial effect, consider adding second-level treatment such as montelukast, as well as referral to allergy or immunology specialist services.

  5. Adverse drug reactions are more common in patients with mast cell disorder, for example, to beta-lactam antibiotics, NSAIDs, codeine, morphine or buprenorphine.

  6. For breathing pattern disorder, consider specialist physiotherapy and/or using alternative therapies such as pranayama breathing and meditation.

  7. In patients expressing distress, significant low mood, anxiety or symptoms of post-traumatic stress disorder, consider mental health assessment.

  8. Over-the-counter supplementation may include vitamin C, D, niacin and quercetin. Be aware of drug interactions.

Recommendations for long Covid Clinics

The experts also advise that long COVID clinics should be led by a doctor with cross-specialty knowledge and experience of managing the condition. They say it is inappropriate for long COVID clinics to be led by mental health specialists, as they do not have the expertise to investigate and manage potential organ damage. They add that 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.

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