The final list comprises 35 recommendations: six relating to clinic organisation (Box 2), 13 to diagnosis of the underlying disorder (Box 3), and 16 to management (Boxes 4 and 5). For a full and printable list of the recommendations, see Supplementary Box S1.8–14
Recommendations relating to clinic organisation (Box 2)
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.15 It cannot therefore be assumed that patients are suffering from a self-limiting post-viral 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.16,17 Patients require a holistic clinical approach that prioritises investigation of potential physical pathology.3,18 The lead clinician should be a doctor, ‘well versed in multisystem disorders’, working across disciplines, and who is able to refer patients to specialists. A responder who runs a long COVID clinic noted the importance of ‘easy access to multi-specialty input without multiple onward referrals (for example, via multi-specialty post COVID MDT [multidisciplinary team])’ and another that ‘isolated consultant clinics (without full MDT) will not work’
Long COVID is not a primary mental health problem, but mental health specialists such as neuropsychiatrists can offer a supporting role to the MDT. Psychological aspects of disease should be managed as part of the recovery process, but not seen as the primary treatment focus.3,4 Panellists were clear that 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.18 Regarding children, a consultant paediatrician should lead the service.3 NICE guidelines recommend considering referral from 4 weeks for specialist advice for children with ongoing symptomatic COVID- 19 or long COVID.4
Recommendations relating to diagnosis of underlying disorder (Box 3)
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, fatigue) that have wide differential diagnoses is not undertaken. Serious conditions, related to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection or not, must be adequately excluded19 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 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 (V/Q) scans are more likely to be indicated.20 In keeping with NICE guidance on asthma management,21 the panel agreed that spirometry with beta-agonist reversibility could be used to diagnose airway hyperreactivity.
Studies on venous thromboembolic disease are limited to patients with acute COVID-19,22 severe disease,23,24 or based on expert opinion, but are an important diagnosis to consider.25 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 relate to acute COVID-19,26,27 and no agreed thresholds are available in long COVID. Doctors working in existing clinics indicated that assessments such as 1-minute sit-to-stand tests28 and 6-minute walk tests29 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-19.30–37 Patients with long COVID (of all ages) have been diagnosed with arrhythmias, autonomic dysfunction, myocarditis, pericarditis, and microvascular ischaemia.38 The latter three may only be seen on cardiac magnetic resonance (MRI) scans (gadolinium-enhanced; stress). Echocardiography has a low diagnostic yield for myocarditis in long COVID,38,39 but diagnosis is important as people experience significant improvement in daily function through specific treatment. Pulmonary embolism appears to be rare more than 6 weeks after the acute illness and there are feasibility concerns about a potential surge of investigations for long COVID. Usual risk-scoring calculators are not valid in this context40 and research is needed.
Autonomic dysfunction, especially manifesting as PoTS, occurs commonly post COVID-19.12 There is a need to consider a differential for tachycardia and palpitations that, in long COVID, includes pulmonary embolus, cardiac, and respiratory causes. It was noted that 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.
As there are no accepted UK criteria for the diagnosis of ‘mast cell activation syndrome’ and it remains an area of controversy, in the present study the term ‘mast cell disorder’ is used to describe patients who present with a range of features listed in recommendation 17 (Box 3).41 The list is not exhaustive and other serious disorders need to be excluded. This area is an important target of mechanistic and potential therapeutic studies in long COVID. Neurocognitive testing is a particularly scarce resource4 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.4,42 NICE guidelines on long COVID advise considering neuropsychometric testing after 6 months if no improvement/worsening of cognitive function, as many will resolve.43 At present, evidence related to joint swelling and arthralgia consists of only case reports, but clinicians should include long COVID in a differential diagnosis of arthritis once other known autoimmune causes have been excluded.44
Recommendations relating to management (Box 4 and 5)
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.45 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. In addition, occupational health service referrals and medical reports supporting the return-towork process are needed.
Employers should discuss with their employee suitable adjustments to aid a return to work, and both parties should be provided with written advice such as the leaflet COVID-19 Return to Work Guide for Recovering Workers by the Society of Occupational Medicine.46 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; this includes secondary care doctors.47 The content of the fit note should be agreed 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.48 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.49,50 From a public health perspective, counting days lost to sickness and lost income on account of long COVID is essential.
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.51 Prolonged illness following SARS-CoV-2 infection is characterised by the development of new symptoms at different timepoints.52 Clinicians need to provide patient ‘safety-netting’ advice and guidance on expected patterns of illness. Although NICE guidance states that new symptoms after 3 months are unlikely to be because of COVID,4 this is not borne out by research53 or patient and specialist experience. The importance of research into long COVID was emphasised by many, which should include quantification of the burden of disease. To this end, one panellist advised that case reporting should be mandatory. The length of the WHO long COVID Case Report Form was noted, however, and flagged as a potential barrier to case reporting in practice. Patients should be made aware of research studies: participation could add meaning to what is often a very negative experience.
Ongoing exertional chest pain may warrant referral to a Rapid Access Chest Pain Clinic and/or cardiac MRI.54 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 anti-anginals may also be helpful, advice from a long COVID assessment clinic needs to be sought.15
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. Although many would advocate specific investigation, NHS autonomic services are patchy, and, if they are not to be overwhelmed, there will be significant educational needs for referring clinicians.55 PoTS treatment can start with fluids, compression, and lifestyle adaptations (for which specific patient support materials are available),56,57 but may need to escalate to medication if symptoms are not improved.58,59 Midodrine may be helpful, although this is only available following secondary care initiating the prescription in many parts of the UK. There is an urgent need for research, education, and clear guidance to help GPs in managing this condition.
Similarly to treating urticaria, mast cell features require two- to fourfold larger doses of antihistamines to suppress them.9 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.60 Unfortunately, H2-receptor antagonists are not readily available in the UK, although at the time of writing famotidine is again available. Further research including clinical trials are needed in this area, but the recommendations represent a simple solution to dealing with very troublesome symptoms in some patients with long COVID.15
The term ‘breathing pattern disorder’ was used in the present study to describe the subjective experience of patients that is not ‘breathlessness’ in the strict sense of the word.61 Its aetiology is unknown but may represent a disorder of central breathing control. Although specialist physiotherapy should be available to patients being seen in clinics, many patients seek help from alternative therapy, such as pranayama breathing. Meditation/mindfulness is promoted in the NHS as an effective therapy for anxiety and the sensation of breathlessness.62
It has been long established that chronic physical diseases have an increased risk of secondary mental health problems. A meta-analysis showed that 36.6% of people with a chronic physical disease had a coexistent mental health disorder.63 Having a mental health disorder should not preclude investigation of any organic disease and unexplained symptoms or 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.64
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.65–67 Further research is needed to confirm or refute the impact of supplements in long COVID.68 Examples of noteworthy interactions with supplements include: niacin causing an increased risk of bleeding events when combined with selective serotonin reuptake inhibitors or non-steroidal anti-inflammatory drugs, increased risk of rhabdomyolysis together with statins,69 and quercetin causing inhibition and induction of various human cytochrome P450 enzymes.70
A recommendation concerning the name (‘long COVID’) did not obtain consensus and was ultimately excluded (Supplementary Table 1: item 37). In Round 1, the named authors suggested the term ‘long COVID’ in preference to ‘Post COVID-19 Syndrome’ and this achieved consensus (94% agreement); in Round 2, the named authors decided to use the recently approved WHO term ‘Post COVID-19 Condition’ but this did not obtain consensus (64% agreement). The naming of the condition is a subject of considerable controversy:71 ‘long COVID’ and ‘long-hauler’ have been adopted by patients in the UK and US, respectively, as neutral terms that make no assumptions about aetiology, presence/absence of ongoing infection, or prognosis.4 NICE suggested adoption of two terms: ‘Ongoing Symptomatic COVID-19’ (4–12 weeks) and ‘Post COVID-19 Syndrome’ (12+ weeks).4 In the US the term ‘Post-Acute Sequelae of COVID-19’ (PASC) has been adopted.72 In contrast, the WHO has adopted ‘Post COVID-19 Condition’ for ICD-11, reflected also in SNOMED coding.73 This enables the creation of subclassifications or SNOMED coordinated terms for any future subcategories of long COVID. Given the desire for international adoption and its use in coding, the authors of the present article accept the use of ‘Post COVID-19 Condition’ as another medical term to describe long COVID.
