COVID-19 seems to be a multisystem disease, sometimes occurring after a relatively mild acute illness.
Clinical management requires whole patient perspective. This relates to patients who have a delayed recovery from an episode of COVID-19 who were managed in the community or in a standard hospital ward.
Broadly speaking, they can be divided into those who have serious sequalae (such as thromboembolic complications) and those with a non-specific clinical picture which is often dominated by fatigue and breathlessness.
The definition post COVID-19 is defined as symptoms extending beyond 12 weeks.
Chronic COVID-19 are those patients who have symptoms extending beyond 12 weeks. During the initial stages of COVID-19 infection, many people were not tested and false negative tests were common. It is therefore suggested that a positive test for COVID-19 is not a prerequisite for diagnosis.
How common is it?
10% of patients who were tested positive for SARS-CoV-2 remained unwell beyond three weeks and a smaller proportion for months.
A recent US study found that only 65% of people had returned to their previous level of health 14 to 21 days after a positive test.
Who and why are affected?
It is not known why in some people recovery is prolonged.
Persistent viraemia, due to weak or absent antibody response, relapse or re-infection, inflammatory and other immune reactions, deconditioning, and mental factors such as posttraumatic stress may all contribute.
Long term respiratory, musculoskeletal and neuropsychiatric sequalae have been described for other coronaviruses such as SARS and MERS and these have pathophysiological parallels for post-acute COVID-19.
What are the symptoms?
Post COVID-19 symptoms vary widely and even the so called mild COVID-19 may be associated with long term symptoms such as:
- Low grade fever
- Fatigue, all of which may relapse and remit.
Other reported symptoms include:
- Shortness of breath.
- Chest pain.
- Neurocognitive difficulties.
- Muscle pains and weakness.
- Gastrointestinal upset.
- Metabolic disruption such as poor control of diabetes.
- Thromboembolic conditions.
- Depression and other mental health conditions.
Skin rashes can take many forms including vesicular, maculopapular, urticarial or chilblain lesions on extremities, the so called Covid toe.
These need to be ordered selectively and for specific clinical indications following careful history and examination.
For example, anaemia needs to be excluded in the breathless patient.
Lymphopaenia is a feature of severe, acute COVID-19.
Elevated biomarkers include:
- CRP – acute infection.
- White cell count – infection or inflammatory response.
- Natriuretic peptides – heart failure.
- Ferritin – inflammation and continuing prothrombotic effect.
- Troponin – acute coronary syndrome with myocarditis.
- D-dimer – thromboembolic disease.
Troponin and D-dimer test may be falsely positive, but a negative result can reduce clinical uncertainty.
For those patients who are not admitted to intensive care, The British Thoracic Society produced guidance on the follow-up of COVID-19 patients. They have suggested that those who had a significant respiratory illness have community follow-up with a chest x-ray at 12 weeks and referral for persistent or progressive symptoms.
Those with evidence of lung damage (such as persistent abnormal chest x-ray and oximeter readings) suggest a referral to a respiratory physician with subsequent early referral to pulmonary rehabilitation supporting recovery.
After excluding serious ongoing complications or comorbidities, patients need to be managed pragmatically and symptomatically with an emphasis on holistic support whilst avoiding over investigation.
Fever for example needs to be treated symptomatically with paracetamol.
Monitoring functional status in post-acute COVID-19 patients is not yet an exact science. However, a post COVID-19 functional status scale has been developed but has not been formally validated.
Referral to specialist rehabilitation services does not seem to be needed for most patients, who can expect a gradual, somewhat protracted improvement in energy levels and breathlessness aided by careful pacing, prioritisation, and modest goal setting. It appears that most patients who were not admitted to hospital recover well within four to six weeks with light aerobic exercise such as walking or Pilates, which is gradually increased in intensity. Those returning to work may need support to negotiate a phased return.
Respiratory symptoms and support
The British Thoracic Society defines chronic cough as one that persists beyond eight weeks.
Up to that time, there are signs of super-infection or other complications such as painful pleural inflammation, cough is best managed with simple breathing control exercises and medications where indicated (such as proton pump inhibitors if reflux is suspected).
A degree of breathlessness is common after acute COVID-19. Severe breathlessness, which is rare in patients who were not hospitalised may require urgent referral. Breathlessness tends to improve with breathing exercises.
Pulse oximeters are extremely useful for assessing and monitoring respiratory symptoms after COVID-19 and their use in the home should not lead to anxiety.
Hypoxia may reflect impaired oxygen diffusion and is a recognised feature of COVID-19. It can be asymptomatic (so called silent hypoxia), or symptomatic. Some oximetry patterns reflecting the increased work of breathing or secondary pathology such as bacteria or pulmonary embolus.
Self-monitoring of oxygen saturations over three to five days should be useful in the assessment and reassurance of patients with persistent dyspnoea in the post-acute phase, especially in those patients whose saturations are normal, and no other cause for dyspnoea is found following thorough evaluation. An exertional desaturation test should be performed as part of the baseline assessment and patients with resting pulse oximetry readings of 96% and above whose symptoms suggest exertional desaturation, such as light headedness or severe breathlessness on exercise. In the absence of contraindications, such patients should be advised a repeat pulse oximeter reading after 40 steps on a flat surface self-testing and then after one minute of doing sit to stand as fast as they can, a fall of 3% in saturation reading on mild exertion is abnormal and requires investigation.
The British Thoracic Society guidelines define the target range of oxygen saturation as 94-98% and a level of 92% or lower as requiring supplementary oxygen unless the patient is in chronic respiratory failure. In the context of a normal assessment without any red flags, an oxygen saturation of 96% or above and the absence of desaturation on exertional tests is very reassuring.
Further investigation or referral in the first six weeks after COVID-19 in such patients is very rarely indicated and regular support by telephone and video consultation is suggested. Oxygen saturations of 95% or below, indicating substantially lower oxygen-haemoglobin desaturation require assessment and investigation. The patients should be provided with the safety netting service. Appropriate adjustments need to be made for patients with lung disease and known hypoxia, in whom the range of 88 to 92% would be considered acceptable.
Recovery after any severe debilitating illness may be prolonged.
Survivors of COVID-19 acute respiratory distress syndrome are at risk of long term impairment of lung function.
Serious interstitial lung disease seems to be rare in patients who are not hypoxic, though data on long term outcomes are not yet available.
Many patients are still recovering spontaneously in the first six weeks after COVID-19 and do not generally require fast track into any pulmonary rehabilitation programme.
Those who have had significant respiratory illness may benefit from pulmonary rehabilitation, defined as a multidisciplinary intervention based on personalised evaluation and treatment which includes, but is not limited to, exercise training, education and behavioural modification designed to improve the physical and psychological conditions of people with respiratory disease.
In the context of COVID-19, rehabilitation should be delivered by various virtual models, including video linked classes and home education booklets with additional telephone support.
The prolonged and profound nature of fatigue in some post-acute COVID-19 patients shares features with chronic fatigue syndrome described after other serious infections such as SARS, MERS and community acquired pneumonia. There is little published research evidence on the efficacy of either pharmacological or non-pharmacological interventions on fatigue after COVID-19.
Patient resources on fatigue management guidance for clinicians on return to exercise and graded return to performance for athletes in COVID-19 are currently based on indirect evidence. For example, for sportsman returning to exercise, which is summarised from the Stanford Hall statement:
- After recovery from mild illness one week of low level stretching and strengthening for targeted cardiovascular sessions.
- Very mild symptoms – limit activity to slow walking or equivalent. Increase rest periods if symptoms worsen, avoid high intensity training.
- Persistent symptoms (such as fatigue, cough, breathlessness, fever) limit activity to 60% of maximum heart rate until two to three weeks after symptoms resolved.
- Patients who had lymphopaenia or acquired oxygen, need respiratory assessment before returning and resuming exercise.
- Patients who had cardiac involvement need cardiac assessment before resuming exercise.
There is much debate and controversy about the role of graded exercise and chronic fatigue generally and in COVID-19 patients in particular. Pending any direct evidence from research studies, it is suggested that exercise in patients should be undertaken cautiously and cut back if patients develop fever, breathlessness, severe fatigue or muscle aches.
It is important to have an understanding and supportive reassurance from the primary care physicians whom are crucial components of the management to these patients.
Cardiopulmonary Complications, Assessment and Management
Perhaps 20% of patients admitted with COVID-19 have clinically significant cardiac occult involvement, maybe even commoner.
Cardiopulmonary complications include myocarditis, pericarditis, myocardial infarction, dysrhythmias and pulmonary emboli.
These may present several weeks after acute COVID-19.
They are commoner in patients with pre-existing cardiovascular disease, but they have also been described in young, previously active patients.
Various pathophysiological mechanisms have been proposed, including viral infiltration, inflammation and microthrombi, and down regulation of ACE2 receptors.
Chest pain is common in post-acute COVID-19.
The Clinical priority is to separate musculoskeletal and other non-specific chest pain. For example, the symptom described by a large patient led survey as lung burn from serious cardiovascular conditions.
This is where clinical assessment of post-acute COVID-19 chest pain should follow similar principles to that for any chest pain presentation. E.g. careful history, taking account of past medical history and risk factors, physical examination, backed up as indicated by investigations.
Where the diagnosis is uncertain, or the patient is acutely unwell, urgent cardiology referral may be needed and specialist assessment and investigations including echocardiography, computed tomography of the chest and cardiac magnetic resonance imaging are required.
COVID-19 is an inflammatory and hypercoagulable state with an increased risk of thromboembolic events.
Many hospitalised patients receive prophylactic anticoagulation.
Recommendations for anticoagulation on discharge vary – but higher risk patients are typically discharged from hospital with 10 days of extended thromboprophylaxis.
If the patient has been diagnosed with a thrombotic episode, anticoagulation and further investigation and monitoring should follow standard guidelines. However, it is not known how long patients remain hypercoagulable following COVID-19.
Left ventricular systolic dysfunction and heart failure after COVID-19 should be managed according to standard guidelines.
Intense cardiovascular exercise must be avoided for three months in all patients after myocarditis or pericarditis; athletes are advised to take three to six months of complete rest from cardiovascular training followed by specialist follow up with return to support guided by functional status, biomarkers, absence of dysrhythmias and evidence of normal ventricular systolic function.
Ischaemic stroke, seizures, encephalitis, cranial neuropathies have all been noted following COVID-19 infection, but fortunately they seem to be rare.
Patients suspected with these serious complications should be referred to a neurologist.
Common non-specific neurological symptoms which seem to co-occur with fatigue and breathlessness, include headache, dizziness and cognitive blunting, so called brain fog.
Until evidence based guidance appears and how to manage or when to refer such symptoms, it is recommended that supportive management of symptomology remains in primary care.
The Older Patient
COVID-19 tends to affect patients who are older more severely.
Those who survive are at high risk of sarcopenia, malnutrition, depression and delirium.
Post COVID-19 chronic pain affects patients when they are any age but seems to be commoner in older patients.
Physical symptoms and the psychosocial impact of disrupted access to healthcare, core personal routines, social interactions, and lay and professional support networks.
Support needs to be personalised with input from a multi professional team for example, general practitioner, district nurse, social worker, rehabilitation team and occupational therapists as required.
Mental Health and Wellbeing
It is well known that individual reactions to the pandemic amongst uninfected individuals include anxiety, stress, conditions related to broken routines, loneliness, and social isolation.
Post-acute COVID-19 is also often associated with low mood, hopelessness, heightened anxiety and difficulty sleeping.
Posttraumatic stress disorder may occur.
Whilst a minority of patients may benefit from referral to mental health services, it is important not to pathologise the majority.
Physical manifestations of COVID-19 may distort responses to assessment tools such as the PHQ-9, which is designed to measure anxiety and depression in a physically healthy population.
Wellbeing, mindfulness, social connection, self-care including diet and dehydration, peer support and symptom control are to be encouraged.
Social and Cultural Considerations
COVID-19 is more common and has a worse prognosis in the acute phase in patients who are poor, elderly, and from certain minority ethnic groups, such as black, south Asian and Jewish.
It is not yet possible to say whether the sociodemographic patterns persist in post-acute COVID-19. However, observation suggests that patients with post-acute COVID-19 are from diverse social and cultural backgrounds – many having comorbidities including diabetes, hypertension, kidney disease or ischaemic heart disease. Many have experienced family bereavements as well as job losses and consequential financial stress and food poverty.
This leads to the strong argument that any services for post-acute COVID-19 patients’ needs to include a multidisciplinary approach with lay care, faith organisations and patient groups being involved.
What is the Extent of Problem?
If 10% of COVID-19 survivors experienced post-acute disease, and from that half of all cases were not formally diagnosed, this translates to about 60,000 people in the United Kingdom with post-acute COVID-19. Many of these patients were young and fit before their illness. They should not be dismissed or treated as hypochondriacs by health professionals.
The natural history of post-acute and chronic COVID-19 is unknown and all these patients should be listened to, supported and managed as appropriate.
Many whose COVID-19 illness is prolonged will recover without any specialist input through a holistic based approach. However, I suggest that we should have an inter-professional community facing rehabilitation team which embraces patient self-management and peer support.
Management of post-acute COVID-19 must occur in conjunction with the management of pre-existing or new co-morbidities.
Dr Paul Ettlinger
Founder – The London General Practice