The ONS predict that that one in five people have symptoms that persist after 5 weeks, and one in ten have symptoms for 12 weeks or longer after acute COVID-19 infection (ONS, 2020). NICE defines post-COVID syndrome or long COVID as symptoms that continue more than 12 weeks after a coronavirus infection, which are not explained by another condition NICE (2020).
- Acute COVID-19: the signs and symptoms of COVID-19 for up to 4 weeks
- Ongoing symptomatic COVID-19: the signs and symptoms of COVID-19 ranging from 4 to 12 weeks
- Post-COVID-19 syndrome: signs and symptoms that develop during or after COVID-19 and continue for more than 12 weeks with no alternative diagnosis.
Despite the fact that one fifth of COVID-19 patients have long COVID, the specific causes remain unclear. What is known is that mast cells are activated by the SARS-CoV-2 virus and the disease is a chronic multisystem disorder with inflammatory action (Afrin et al, 2020; Wang et al, 2020). Certainly following direct viral invasion thrombosis, hyper activation of the immune system and hormonal dysregulation have led to the acute symptoms of COVID-19 but it is unclear what plays a part in long COVID (Yelin et al, 2020). It is also unclear why some people recover quicker than others. Certainly persistent viremia due to weak or absent antibody response, deconditioning, post-traumatic stress and an acute immune response may all contribute to the recovery time (Greenhalgh et al, 2020). The symptoms also vary from person to person but there is an extensive list of common symptoms mirroring the complex impact of COVID-19 and outlined by NICE (2020) (Box 1). It certainly encompasses a plethora of debilitating symptoms which can last for weeks (Dani et al, 2021).
Box 1.Common long COVID symptoms
- Fatigue
- Shortness of breath
- Chest pain or tightness
- Problems with memory and concentration (‘brain fog’)
- Insomnia
- Heart palpitations
- Dizziness
- Pins and needles
- Joint pain
- Depression and anxiety
- Tinnitus, earaches
- Nausea, diarrhoea, stomach aches, loss of appetite
- Night sweats / persistent or intermittent pyrexia
- Headaches
- Unexplained rashes
- Anxiety and depression
- Investigations.
Source: Mahase, 2020; NICE et al, 2021; Yelin et al, 2020
Investigations
The new guideline for NICE (2021) recommends that patients presenting with new or ongoing symptoms 4 weeks or later after an initial COVID-19 infection should have the following investigations done; a full blood count, kidney and liver function tests, a C-reactive protein test, and an exercise tolerance test (recording level of breathlessness, heart rate, and O2 saturation). A chest x-ray should be offered to all patients by 12 weeks after acute infection if they have continuing respiratory symptoms. These investigations should be done to rule out acute, life-threatening complications or identify any unrelated diagnosis (NICE, 2021). It is also important not to over investigate (Gemelli, 2020).
Box 2.Investigations
- Consider offering blood tests including:
- Full blood count
- Urea and electrolytes
- Liver function tests
- C-reactive protein test
- Ferritin lB-type natriuretic peptide
- Thyroid function tests.
- It may be appropriate to consider an exercise tolerance test and ECG to assess breathlessness, heart rate changes, and oxygen saturation
- Patients with postural symptoms need an assessment of lying and standing blood pressure to exclude postural hypotension, postural tachycardia, or other forms of autonomic dysfunction
- If a person has persisting respiratory symptoms lasting longer than 12 weeks after acute COVID-19 they should have a chest X-ray.
Adapted from NICE, 2021
Management
After excluding serious ongoing complications or comorbidities patients should be managed holistically (Gemelli, 2020). The key aspect of management of this condition is self-manage of symptoms with realistic goals (NICE, 2020). Patients can be taught to identify what causes the fatigue or the other symptoms, and try to avoid those things (Nabavi, 2020). It is a slow recovery – a long haul marathon rather than a sprint. Patients should have a bespoke rehabilitation and management plan that includes goals and support for symptom management for all the presenting symptoms such as breathlessness, fatigue and ‘brain fog’. People with long COVID symptoms can be offered specialist help at clinics across England (NHS England, 2020). In Northern Ireland, however, the decision has been made that those recovering from long COVID should be cared for by their GPs. The challenge is that this is such a new disease and many of the patients are ‘expert patients’. Callard and Perego (2021) suggest that long COVID is the first illness identified by patients through Twitter and other social media. Garg et al (2020) suggests that long COVID is a multisystem syndrome and needs a multifaceted approach to tackle the physical, cognitive, psychological, social, and vocational aspects of this condition. There needs to be a shared decision-making approach with the General Practitioner that includes follow up and review, particularly if symptoms of COVID-19 persist beyond 4 weeks (NICE, 2021). If that is the case, then a clear pathway needs to be developed to support these patients that includes recommended treatments (Ladds et al, 2021).
It is recommended that clinicians use comprehensive screening tools such as the C19-YRS (Yorkshire Rehabilitation Screen) to identify persistent symptoms and rehabilitation needs and then refer to an integrated COVID-19 rehabilitation pathway (Sivan et al, 2020). C19-YRS is a multi-system telephone screening tool which has been developed by the multi-disciplinary-rehabilitation teams from Leeds, Airedale and Hull NHS Trusts to help assess symptoms and support rehabilitation interventions for these individuals based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) Framework (Sivan et al, 2020).
It is also unclear whether over-the-counter vitamins and supplements are helpful for these symptoms (NICE, 2020) but there is some evidence that Zinc can be considered as a potential supportive treatment due to its anti-inflammatory, antioxidant and direct antiviral action (Zhang and Liu, 2020). Certainly vitamin D deficiency is associated with COVID-19 infections and supplements have been shown to have beneficial effects in patients across all ages groups and in individuals with pre-existing chronic conditions (Charan et al, 2012; NICE 2020b). There is also some debate about the effectiveness of vitamin C (Adams et al, 2020). Another product is glutathione. Glutathione is a tripeptide of cysteine, glycine. Glutamate is an antioxidant that plays a crucial role in antioxidant defence against oxidative damage of cells, making it a considered as a treatment of COVID-19 (Polonikov, 2020). As a non-medical prescriber one option would be to prescribe micronutrient supplementations such as ‘Forceval’ as this can support the immune system (Gasmi et al, 2020; McAuliffe et al, 2020).
COVID-19 effects the intestinal microbiota so probiotics have been recommended as a potential treatment option (Bottari et al, 2020; Morais et al, 2020). Probiotics have also been linked with improving the host innate immune response as well as anti-inflammatory effects and is therefore considered as a prophylactic treatment option to combat the pathogenesis of COVID-19 (Mrityunjaya et al, 2020; Zafar et al, 2020).
There is also some debate for the use of magnesium supplementation for the neuropathic pain experienced by sufferers of long-COVID. It has been used for several years for its antinociceptive effect on neuropathic and inflammatory pain (Sebro et al, 2017; Tang et al, 2020). It is also thought to provide supportive treatment in patients with COVID-19 as it supports the respiratory system (Tang et al, 2020).
Medication
The information about treatment options is dependent on the patient's symptoms. The research is constantly being updated as this is such a new illness, so it is also up to us as clinicians to keep updated with new options. COVID-19 can result in a ‘cytokine storm’ that leads to worse clinical outcomes but in long COVID the issue is a “rain of cytokine” which leads to persistent chronic inflammation that causes asthenia and impacts the process of healing (Schäfer et al, 2020).
Montelukast has been found to attenuate the signalling of NF-κB and modulates cytokine production and is helpful for those who have asthma and covid-19. (Fidan and Aydoğdu, 2020; Sanghai and Tranmer, 2020). It has been suggested that Montelukast has anti-inflammatory effects, suppresses oxidative stress and reduces the effect of cytokine production limiting the progression of the disease (Fidan & Aydoğdu, 2020). Most studies on the use of montelukast and COVID-19 look at the acute episode of the infection (Aigner et al, 2020; Khan et al, 2021; Sanghai et al, 2020). Certainly, Barré et al (2020). Found that montelukast improved COVID-19 outcomes as it created a limitation of the cytokine storm, but further studies of this drug need to be done looking at its effects on cytokine rain.
Antihistamines have been found to be effective with direct antiviral activity against COVID-19 in vitro (Reznikov et al, 2020). Antihistamines are thought to control the immune response and cytokine storm in COVID-19 so one may presume they can also reduce the impact of cytokine rain (Afrin et al, 2020; Eldanasory et al, 2020). Larsen et al (2021) found that antihistamines were prescribed to patients with long COVID for the mast cell activation syndrome associated with this illness. There is certainly anecdotal reports of gradual clinical responses to histamine receptor in this patient group (Glynne et al, 2021). There is a need for more research in the role of antihistamines and long COVID.
A small multicentre randomised case-control study of 18 patients with COVID-19 anosmia or severe hyposmia were found to improve with systemic prednisone and nasal irrigation with betamethasone (Vaira et al, 2020). Walker et al (2020) advise using nasal steroids rather than systemic steroids. There are few ¬¬evidence-based protocols for the management of anosmia in COVID-19. Treatment options are intranasal steroid therapy and smell training (Touisserkani and Ayatollahi, 2020; Zheng et al, 2021).
Conclusions
Post-COVID syndrome or long COVID is defined as an illness where symptoms continue more than 12 weeks after a coronavirus infection, which are not explained by another condition NICE (2020). It is predicted one in five people have symptoms that persist after 5 weeks, and one in ten have symptoms for 12 weeks or longer after acute COVID-19 infection (ONS, 2020). Recovery and symptoms and it encompasses a plethora of debilitating symptoms which can last for weeks (Dani et al, 2021). The key aspect of management of this condition is self-manage of symptoms with realistic goals (NICE, 2020). NHS England (2020) recommend referral to regional long COVID hubs with expertise form the multidisciplinary team but in Northern Ireland care is delivered in Primary Care. Certainly the clinician needs to keep up to date with current treatment of symptoms of long COVID. There also needs to be clear pathways to support these patients.
Key Points
- As one in ten have symptoms for 12 weeks or longer after an acute COVID-19 infection (ONS, 2020), it is predicted that there will be over a million people who have long covid within the next year.
- Garg et al (2020) suggests that long COVID is a multisystem syndrome and needs a multifaceted approach to tackle the physical, cognitive, psychological, social, and vocational aspects of this condition.
- There needs to be a clear pathway for treatment in primary care.
CPD reflective questions
- Can you differentiate between the symptoms of COVID-19 and long covid?
- How do you think this illness affects a patient's health and wellbeing?
- Are you aware of long covid pathways where you work? If not try and identify them
- As long Covid is a new illness the research about it is constantly changing. What interesting study have you recently read?