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Living Evidence - post acute sequelae of COVID-19

Living evidence tables provide high level summaries of key studies and evidence on a particular topic, and links to sources. They are reviewed regularly and updated as new evidence and information is published.

Post-acute sequelae of COVID-19 (PASC) generally refers to a syndrome characterised by persistent and prolonged effects after acute SARS-CoV-2 infection. PASC is now recognised as a multi-organ disease with a broad spectrum of manifestations. The National Institute for Health and Care Excellence (NICE) rapid guideline noted COVID-19 disease spans:

  • acute COVID-19: signs and symptoms of COVID-19 for up to four weeks
  • ongoing symptomatic COVID-19: signs and symptoms of COVID-19 from four to 12 weeks
  • post-COVID-19 syndrome: signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis.

Development of PASC may be linked to symptomatic COVID-19 infection, hospitalisation, and severity of illness. There is also some evidence that it is associated with gender, specifically that women have a higher incidence of PASC^, and moderate and severe obesity.

Emerging evidence on developing a framework for a coordinated national health policy action and response and research priorities for PASC.

This table includes information on ongoing symptomatic COVID-19 and PASC as defined by NICE. It focuses on symptoms, assessment and management.

Checks for new content are conducted each fortnight, and any updates that occur during that time are highlighted.

Time periodSymptomsAssessmentManagement

One month

Approximately 40% of people experienced persistent cough at two to three weeks following initial symptoms. Often resolves by three months.

Approximately 40% of people report olfactory and gustatory symptoms. Majority have complete or near-complete recovery at one month following acute illness.

2.5% cumulative incidence of thrombosis at 30 days following discharge.

A cohort study of US veterans found increased risk of kidney outcomes post-COVID-19.

Assessment scheduled approximately one week following discharge from hospital for a patient with more severe COVID-19 requiring hospitalisation and three weeks following onset of illness for a patient who is older or with comorbidities and did not require hospitalisation.

Comprehensive history of the patient's acute COVID-19 illness.

Clinical assessment for respiratory, psychiatric and thromboembolic sequelae, as well as rehabilitation needs.

Need for laboratory testing is determined by the severity and abnormal test results during patient’s acute illness, and current symptoms. For most people who have recovered from mild disease, laboratory testing is not necessary. Blood tests including a full blood count, kidney and liver function tests, C‑reactive protein test, ferritin, B‑type natriuretic peptide (BNP) and thyroid function tests may be offered.

Clinical evaluation of cardiopulmonary symptoms.

Evaluation of exercise capacity and oxygenation.

Urgent referral of people with ongoing symptoms or suspected PASC to relevant acute services if they have symptoms that may be caused by an acute or life threatening complication including severe hypoxaemia, severe lung disease, cardiac chest pain or multisystem inflammatory syndrome in children.

Advice on self-management should be provided to people with ongoing symptomatic COVID-19.

Cough is managed in a similar fashion to cough in patients with post-viral cough syndrome and typically comprises over-the-counter cough suppressants.

For people with olfactory and gustatory symptoms, symptoms usually resolve slowly over several weeks and do not require intervention. There is a Cochrane living systematic review on the efficacy of interventions for persistent olfactory dysfunction.

People with a need for rehabilitation services are typically referred within 30 days of recovery from initial infection. Rehabilitation programs generally last 6-8 weeks, and may include inpatient, outpatient, in-person, web-based or home rehabilitation.

Patients diagnosed with documented thromboses are managed in a similar way to thrombosis in non-COVID-19 patients. Direct oral anticoagulants and low-molecular-weight heparin are preferred anticoagulation agents over vitamin K antagonists.

Extended thromboprophylaxis considered for high-risk survivors.

Social, financial and cultural support.

Three months

A Lancet Regional Health Europe prospective cohort study found 55% of participants reported not feeling fully recovered from COVID-19 at 3 months post-discharge, and 93% reported persistent or new symptoms.

The most common symptoms were fatigue (83%), shortness of breath (dyspnea) (54%), and problems sleeping (46%). The US Centers for Disease Control and Prevention conducted a national survey and reported similar results.

Chest discomfort persists in 12% to 22% of patients approximately 2-3 months after acute COVID-19 infection.

A systematic review of cardiac sequelae of COVID-19 found medium-term (3-6 months) impacts included diastolic dysfunction and COVID-19 survivors were at a higher risk of developing heart failure, arrythmias and myocardial infarction.

Common non-specific neurological symptoms include headaches, dizziness, and cognitive blunting (“brain fog”).

Neurocognitive symptoms are reported in over 15% of people including concentration and memory problems which persist for six weeks or more after discharge.

Psychological symptoms (such as anxiety, depression, PTSD) are common after acute COVID-19 infection. Over 20% of people reported psychological symptoms or distress. This was higher (over 45%) in people who were in ICU.

Thromboembolism, chronic kidney disease and hair loss also reported.

Case reports of diabetic ketoacidosis reported 2-3 months after COVID-19 diagnosis.

Symptom assessment may include 6 minute walk test, pulmonary functions tests, chest X-ray, pulmonary embolism work up, echocardiogram and high-resolution computed tomography of the chest at 4-6 weeks and 12 weeks post discharge.

Screening for functional impairment.

Chest radiography at 12 weeks following discharge to ensure complete radiographic resolution. Echocardiogram at 4–12 weeks may be considered.

Pulmonary function testing at 6-12 weeks following hospital discharge.

Complete neurological history and examination for neurologic and neurocognitive sequalae.

Evaluation for signs of hypercoagulability and thromboses.

People may also be assessed for other symptoms including renal, hepatic, endocrine, gastrointestinal, dermatologic, sleep, psychological and quality of life.

People with impaired renal function may benefit with early follow up with nephrologist after discharge of people with COVID-19 and acute kidney injury.

Serologic testing for type 1 diabetes-associated autoantibodies obtained in patients with newly diagnosed diabetes mellitus in the absence of traditional risk factors for type 2 diabetes.

Management for fatigue includes encouragement of rest, good sleep hygiene, and specific fatigue management strategies.

Management for dyspnea is similar to that in non-COVID-19 patients and may include pharmacotherapy, breathing exercises and consideration of pulmonary rehabilitation.

Chest discomfort does not generally require treatment. For severe discomfort NSAIDS may be administered.

Neurologic complications following COVID-19 should be managed in the same way as with other patients. People with severe psychiatric symptoms or who are at risk of self‑harm or suicide should be referred urgently for psychiatric assessment.

Six months

Approximately 25% of people admitted to hospital for COVID-19 still had three or more persistent symptoms at six months.

A systematic review reported that fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression, and impaired concentration were present in more than 20% of included patients.

Other persistent symptoms can include loss of sense of smell or taste, worsened health related quality of life, and sleeping difficulties.

Abnormal lung functions and structural changes were reported up to six months after hospitalisation in mild-to-critical COVID-19 patients.

A prospective cohort study of patients with COVID-19 associated acute respiratory distress syndrome reported poor exercise capacity, health status, and lower health related quality of life scores compared to the general population at 8 months follow-up. More than 90% presented with mental health disorders.

A 6-month follow-up study of previously hospitalised COVID-19 patients found 40% of patients had neurological abnormalities, including hyposmia, cognitive deficits, postural tremor, and subtle motor/sensory deficits.

3% of patients noted a skin rash at six months follow-up.

Children

A longitudinal cohort study from Switzerland found low prevalence (0% to 27%) of PASC symptoms in children and adolescents.

An Italian study found 29 of 68 (42.6%) children still had at least one PASC symptom more than four months after COVID-19 diagnosis.

An Iranian study found 26 of 58 (44.8%) children and adolescents reported PASC symptoms at least three months after discharge from hospital, including fatigue, shortness of breath, exercise and walking intolerance, and weakness.

A Swedish study found 12 of 55 (22%) had persistent symptoms.

A large preprint study of UK children and young people reported 1 in 7 (14%) may still have symptoms after 3-4 months.*

Three separate UK preprint studies found that the rate is probably below 10% and perhaps as low as 1%.*

High-resolution computed tomography of the chest.

Referral to an evaluation in a specialised outpatient COVID-19 recovery clinic, or relevant subspecialty clinic, for patients with persistent symptoms lasting beyond 12 weeks.

Management for fatigue, dyspnea and neurologic complications is similar to that in non-COVID-19 patients.

Tailored rehabilitation including light aerobic exercises and breathing exercises.  Pharmaceutical treatments including paracetamol and non-steroidal anti-inflammatory drugs may be used to manage specific symptoms e.g. fever.

12 months

Approximately 50% of people reported persistence of at least one symptom at 12 month follow up, most commonly fatigue, followed by smell or taste impairment.^

Case report of ongoing symptoms including breathlessness, brain fog, fatigue, headache, poor temperature control, eye site deterioration, tingling in face, swollen glands and nausea reported over 12 months post COVID-19.

A cohort study comparing symptoms between 6 months and 12 months found that patients with at least one PASC symptom decreased from 68% to 49%, dyspnoea increased slightly from 26% to 30%, and more patients had anxiety or depression at 12 months (26%) compared with 6 months (23%).

Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work (88%) and life.

High-resolution computed tomography of the chest.

More than 50 long-term effects of COVID-19 have been reported in the literature. Only commonly reported and emerging symptoms have been included in the living table.

Notes

* Preliminary data, not fully established, in some cases small numbers or short follow up; interpret with caution

^ Commentary, grey literature, pre peer review or news

Living evidence tables include some links to low quality sources and an assessment of the original source has not been undertaken. Sources are monitored daily but due to rapidly emerging information, tables may not always reflect the most current evidence. The tables are not peer reviewed, and inclusion does not imply official recommendation nor endorsement of NSW Health.

Last updated on 20 Sep 2021

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