Approach

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational guidance:

Opvolging en revalidatie van patiënten met aanhoudende klachten na COVID-19 in de eerste lijnPublished by: KU Leuven | Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2023Suivi et revalidation des patients présentant des symptômes persistants après la COVID-19 en première lignePublished by: KU Leuven | Groupe de Travail Développement de recommmandations de première ligneLast published: 2023

Long COVID is defined as symptoms persisting after 4 weeks or 3 months, depending on the definition chosen (see Definition).[2][4] The majority of people will recover from coronavirus disease 2019 (COVID-19) within the first 12 weeks. After 12 weeks, patients may still recover but persistent illness becomes more likely or patients may improve but at a slower rate.[4][78]

It is a heterogeneous condition that encompasses a wide spectrum of new or persistent symptoms following acute COVID-19 and includes individuals who were mildly ill and did not require care during the acute period of infection as well as those recovering from critical illness.[79]

Use a holistic, person-centred approach that includes a comprehensive clinical history and appropriate examination.

Long COVID is a diagnosis of exclusion.[80] The primary goal of initial evaluation should be to focus on ruling out contributory factors that may be leading to ongoing symptoms (e.g., cardiac, pulmonary, and rheumatological processes).[2] Individuals with long COVID should also be screened for other post-viral conditions including myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome.[4]

Refer the patient to a specialist when the diagnosis is uncertain, there is concern for underlying organ-specific dysfunction (e.g., cardiac or pulmonary), or when symptoms are progressing or severe.[81]

History

Ask if the patient has ever had confirmed or suspected COVID-19. A positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral test is not necessary to establish a diagnosis of long COVID. A long COVID diagnosis can be made on the basis of a previous patient-reported or clinical diagnosis of COVID-19.[4][39]

Take a directed history aimed at the chief complaint for any patient presenting with concern for long COVID.

  • Ask about the frequency and severity of the symptoms (so that management of the most frequent and severe can be prioritised) and whether anything triggers, alleviates, or aggravates the symptoms.[1][81]

  • Ask how symptoms, such as fatigue, affect the patient’s normal day-to-day functioning and impact on work or school.[1][82]

    • The severity and wide spectrum of symptoms can have a substantial impact on the patient’s quality of life.[4]

  • Ask about the course and severity of the patient’s acute COVID-19 episode (if known).[1]

  • Enquire about the patient’s activity level since COVID-19 and any new diagnoses or complications acquired since the episode.[83]

Where possible, perform a comprehensive review of systems, bearing in mind the diverse nature of persistent symptoms associated with long COVID.[4] However, due to time or resource constraints it may be necessary to prioritise which symptoms to focus on. Recognise that the symptoms of long COVID can have a major impact on the patient’s day-to-day life, ability to function, and sense of wellbeing. Ask the patient which symptoms are most troubling and use this to direct the further assessments, if needed. Consider using symptom questionnaires together with clinical assessment to identify the presence of symptoms and for changes over time.[1] A selection of recommended standardised measures and scales related to specific clinical symptoms are listed below (this is not an exhaustive list).[4][84][85]

Respiratory function

  • Modified Medical Research Council Dyspnoea Scale Opens in new window

  • Borg Dyspnea Scale

  • Multidimensional Dyspnea Profile[83]

Fatigue

Post-exertional symptoms

Cardiovascular symptoms

Cognitive function

Mental health

Nervous system symptoms

  • Central Sensitization Inventory

Pain

  • Brief Pain Inventory

  • Visual Analogue Scale

Work/occupation

Recovery

  • Recovery scale for COVID-19

Multiple domains

The presentation of long COVID is varied, with over 200 symptoms having been linked to the condition.[13] Symptoms may fluctuate, persist, relapse, and remit over time.[3]

Prevalence rates of long COVID symptoms have been limited by methodological issues, including lack of control groups, unknown prevalence of pre-COVID symptoms, inconsistent assessments, and heterogeneity of populations being studied. Despite these limitations, the most common symptoms of long COVID are generally reported to include:

  • Fatigue/weakness (31% to 58%)[1][8][18][38][79][80][81][86]

  • Cognitive impairment (brain fog) (12% to 35%)[8][38][80][81][86]

  • Impaired sleep (11% to 44%)[38][79][80][81]

  • Headache (up to 79%)[1][38]

  • Dizziness (up to 48%)[1][8][80]

  • Dyspnoea (22% to 40%)[1][18][38][79][80][81][86]

  • Loss of concentration (60%)[1]

  • Cough (7% to 29%)[1][80]

  • Anosmia/dysgeusia (10% to 46%)[1][18][38][80]

  • Pain (including arthralgias and myalgias) (9% to 19%)[18][79][80]

  • Chest pain (6% to 17%)[18][38][80][81]

  • Post-exertional malaise[8][86]

  • Anxiety/depression[38][81]

Other common symptoms include:

  • Palpitations[81]

  • Thirst/dry mouth

  • Loss of sexual drive or capacity

  • Numbness/tingling

  • Hair loss

  • Abnormal movements

  • Gastrointestinal symptoms[8][81]

The following symptoms and signs are less commonly reported in children and younger people:[1]

  • Dyspnoea

  • Persistent cough

  • Pain on breathing

  • Palpitations

  • Heart rate variations

  • Chest pain.

Ask the patient about comorbidities and review any drugs that the patient is taking as these may be contributing to ongoing symptoms.[82]

[Figure caption and citation for the preceding image starts]: Co-occurrence network of symptom clusters 6-12 months after acute infection. Outer circles represent individual symptoms. Circle area represents proportion of patients with that symptom. These are linked to inner circles, which represent symptom clusters. Width of link lines again represents proportion of patients with that symptom. Circle area for clusters represents proportion of patients with at least one symptom from that cluster. Central links between symptom clusters represent co-occurrence of symptom clusters. Link width represents degree of co-occurrence. Based on data from 11,536 participants. Only symptoms not present before acute SARS-CoV-2 infection were consideredBMJ 2022 Oct 13:379:e071050; used with permission [Citation ends].com.bmj.content.model.Caption@683aa3c4

Risk factors

Risk factors for long COVID include having a more severe acute COVID-19 illness (including being hospitalised), partial vaccination or absence of vaccination against COVID-19, and female sex. Other risk factors include age older than 40 years, body mass index >30 kg/m², being a current smoker, and presence of comorbidities.[10][33][34][35][36][37][38][39][40][41][42][43][44]

Physical examination

Ideally, perform comprehensive cardiopulmonary, neurological, and rheumatological examinations. Further direct the physical examinations depending on the presenting symptoms.[4] See Assessment of dyspnea, Assessment of fatigue, Assessment of dizziness, Assessment of chronic cough, Assessment of chest pain.

Obtain vital signs, including heart rate, blood pressure, respiratory rate, pulse oximetry, and body temperature.[4][81][83]

For patients presenting with activity intolerance, fatigue, cognitive impairment, generalised malaise, dyspnoea, dizziness, and/or palpitations, obtain a 10-minute orthostatic stand test with measurement of heart rate and blood pressure at 5 minutes after laying supine and 1, 2, 5, and 10 minutes after standing.[81][87] This will help to differentiate cardiovascular symptoms from autonomic dysfunction.[81] A sustained drop in blood pressure of ≥20/10 mmHg within 3 minutes of standing or on a tilt table test indicates orthostatic hypotension. A sustained heart rate increase ≥30 beats per minute within 10 minutes for adults (≥40 beats per minute for adolescents aged 12-19 years) of standing or on a tilt table test is an indicator (amongst other criteria) for postural orthostatic tachycardia syndrome.[87]

Obtain standardised measures of endurance and activity performance at the initial examination.[81] For individuals with generalised malaise, fatigue, dyspnoea, or exertional intolerance, use a test such as a 6-minute walk test with assessment of ambulatory oxygenation, 30-second (or 1-minute) sit-to-stand test, a 2‐minute step (seated or standing), or a 10-metre walk test.[4][82] Consider the degree of post-exertional malaise prior to any testing of endurance and activity performance. Use caution as the patient may not have the stamina or capability to perform these physical tests and such tests may worsen the patient’s symptoms of fatigue or malaise in the following days.[4] Additional planning and modifications of the tests may be required in patients with post-exertional malaise.[4]

Repeat the measures at follow-up to compare with previous results and guide intervention.[81] Bear in mind that a combination of factors, such as fatigue and dyspnoea, may contribute to a patient’s limited activity level.

Initial investigations

Long COVID is primarily a clinical diagnosis. Investigations should be directed at ruling out other, directly treatable conditions.[80] Tests should be selective and tailored to the patient’s symptoms.[1][78][80] There is no direct testing for long COVID and no definitive test to rule in or rule out the condition.[4]

Laboratory tests and imaging are typically normal. Normal objective test results or findings should not be used to dismiss the presence or severity of a patient’s symptoms or as the only measure of their overall wellbeing.[4]

For all patients with suspected long COVID, obtain a basic laboratory panel including:[1][4][39][80][82][88]

  • Full blood count

  • Comprehensive metabolic panel

  • Creatine kinase

  • C-reactive protein

  • Erythrocyte sedimentation rate

  • Ferritin

  • Thyroid stimulating hormone and free T4

  • Vitamin D and B12.

A positive SARS-CoV-2 viral test is not necessary to establish a diagnosis of long COVID. A long COVID diagnosis can be made on the basis of a previous patient-reported or clinical diagnosis of COVID-19.[4][39]

Other investigations

Subsequent testing is based on presenting symptoms and degree of clinical suspicion. Generally, additional testing is not needed unless there is a specific condition that there is concern for. Risks of excess testing include increased risk of incidental findings, anxiety, radiation exposure, cost, time, and energy.[4][39][82]

For persistent dyspnoea, obtain pulmonary function testing and consider (in addition to the initial investigations):[1][78][80][83][88]

  • B-type natriuretic peptide

  • D-dimer

  • Chest radiography

  • Chest computed tomography (CT)

  • Transthoracic echocardiogram.

In a group of hospitalised patients evaluated by chest CT, 55.7% had residual abnormalities on chest CT at 3 months.[89] After 1 year, 32.6% of hospitalised patients still had residual CT abnormalities (primarily fibrotic changes). Abnormalities were more frequent in patients who had severe/critical disease compared with mild/moderate disease.[90] However, the prevalence of lung sequelae at 1 year is highly heterogeneous among studies.[91]

For persistent cardiac symptoms, consider (in addition to the initial investigations):[81]

  • B-type natriuretic peptide

  • D-dimer, troponin

  • Chest x-ray

  • Electrocardiogram

  • Transthoracic echocardiogram

  • Exercise stress test

  • Cardiopulmonary exercise test

  • Ambulatory heart rate monitoring

  • Cardiac magnetic resonance imaging (MRI).

For persistent symptoms of autonomic dysfunction, consider (in addition to the initial investigations):[87]

  • Morning cortisol

  • Anti-nuclear antibodies

  • D-dimer (if concern for pulmonary embolism)

  • Autonomic reflex testing

  • Tilt-table testing

  • Electrocardiogram

  • Ambulatory heart rate monitoring

  • Transthoracic echocardiogram.

For persistent cognitive issues, consider (in addition to the initial investigations):[92]

  • Thiamine

  • Folate

  • Homocysteine

  • Magnesium levels

  • Neuropsychological testing

  • MRI of the head.

For rheumatological symptoms, consider (in addition to the initial investigations):[82][93]

  • Imaging of affected joints

  • Anti-nuclear antibody test

  • Rheumatoid factor

  • Anti-cyclic citrullinated peptide

  • Anti-cardiolipin antibody.

For persistent fatigue, consider (in addition to the initial investigations) an overnight sleep study (if suspecting sleep apnoea).[82]

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