Approximately 10-to-30 per cent of patients who have tested positive for Covid-19 remain unwell beyond three weeks and a smaller proportion – about 10 per cent – experience symptoms for months, which may be relapsing-remitting in nature.
Coronavirus disease 2019 (Covid-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly transmissible viral illness responsible for an ongoing global pandemic. Initial variants of the virus including the Alpha, Beta, and Delta variants have been associated with a high morbidity and mortality predominantly related to respiratory disease.1 After the acute illness, 10-to-30 per cent of individuals suffer from persistent symptoms such as shortness of breath, chest discomfort, fatigue, and neurocognitive difficulties. Ongoing symptoms may occur following severe disease requiring hospitalisation and in those with a milder initial illness without hospitalisation. The post-acute sequalae of Covid-19 infection, also termed ‘long Covid’ or ‘post-Covid-19 condition’ when they persist beyond three months, can significantly affect quality-of-life (QoL) and productivity for many people and are a major concern both for individuals and healthcare planning. While there are no evidence-based treatment options as yet, there is a potential role for structured rehabilitation to improve symptoms and QoL in the condition. Case Report 1 and Case Report 2 are fictionalised cases representative of the typical patients frequently encountered in the post-Covid pulmonary rehabilitation programme (PRP) in our institution.
As of late May 2022, over 1.56 million Covid-19 cases had been reported in Ireland with more than 37,000 hospitalisations and over 7,300 deaths. However, the vast majority of infections are mild or moderate in nature and do not require hospitalisation. Common symptoms of acute Covid-19 infection (≤four weeks from infection onset) include fever, cough, shortness of breath, chest discomfort, and fatigue. For some individuals, the effects of Covid-19 can last well beyond the immediate illness, even in cases where this was mild. Approximately 10-to-30 per cent of patients who have tested positive for SARS-CoV-2 virus remain unwell beyond three weeks, and a smaller proportion – about 10 per cent – experience symptoms for months, which may be relapsing-remitting in nature.
The UK’s National Institute for Health and Care Excellence (NICE) defines long Covid as 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.2 Similarly, the World Health Organisation (WHO) consensus definition of the post-Covid condition is as occurring “in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from the onset, with symptoms that last for at least two months and cannot be explained by an alternative diagnosis”.3
Over 205 symptoms in 10 organ systems have been described in long Covid, and symptoms may fluctuate over time. The most prevalent symptoms reported are fatigue, shortness of breath, chest pain, post-exertional malaise, smell and taste disturbances, headache, poor concentration and ‘brain fog’, and sleep disturbance. Many individuals with long Covid are either unable to return to work or require an adjusted or reduced work schedule, with significant financial and workforce implications.
The underlying pathophysiology of long Covid remains unknown. A variety of mechanisms have been postulated including organ damage during the acute infection, a persistent hyperinflammatory state, inadequate antibody response, and ongoing viral activity. There may also be contributions from co-morbidities and deconditioning related to hospitalisation when present. The SARS-CoV-2 entry receptor ACE2 is widely expressed, potentially explaining persistent symptoms related to multiple organs such as the lungs, heart, and brain. Research into the pathogenesis of long Covid is urgently needed to better understand the symptoms and natural history of the condition, assist in prognostication, and to aid in development of effective therapies.
Long Covid sufferers can be divided into two main categories. The first group is those who developed a moderate-severe Covid-19 infection with direct organ injury related to the virus and/or deconditioning related to the acute illness leading to persistent symptoms. These individuals frequently have evidence of persistent radiological and/or physiological abnormalities and may be older with other co-morbidities. Based on initial illness severity, it could be anticipated that this group may have ongoing pulmonary abnormalities and require pulmonary rehabilitation.
The second group comprises those with an initial mild or even asymptomatic illness managed in the community whose symptoms persist from the acute illness or appear after recovery. They may present with prolonged multisystem involvement and significant disability and the functional disability may appear out of proportion to the degree of imaging and/or lung function impairment.
In both cases structured rehabilitation programmes and self-management strategies can play an important role in recovery from ongoing symptoms and functional impairment.
A 73-year-old male ex-smoker (30 pack years) with a history of Global Initiative for Chronic Obstructive Lung Disease (GOLD) II chronic obstructive pulmonary disease (COPD) with additional co-morbidities, including hypertension and diabetes, developed Covid-19 infection during the first wave of the pandemic in March 2020.
He was hospitalised and developed respiratory failure, which was managed with high-flow oxygen therapy and did not require mechanical ventilation. On discharge from hospital he remained dyspnoeic and required 2L of oxygen (O2) for exertion.
On assessment three months after his acute illness, he reported ongoing exertional breathlessness, anxiety, and fatigue. As a result he was referred for additional evaluation and outpatient pulmonary rehabilitation.
Chest x-ray demonstrated persistent, but improving, pulmonary infiltrates and pulmonary function testing revealed moderate obstruction on spirometric testing consistent with his known GOLD II COPD.
However, the diffusing capacity of the lung for carbon monoxide (DLCO) was reduced at 45 per cent of predicted; 10 per cent lower than prior testing. He walked a distance of 210m on a pre-rehabilitation six-minute walk test (6MWT) performed on 2L of O2.
Respiratory questionnaires scores, including the COPD assessment tool (CAT), the St George’s Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Scale (HADS), and the Post-Covid Functional Status (PCFS) scale, demonstrated significant symptom burden pre-rehabilitation.
A 42-year-old female who never smoked, with no significant past medical history. She was very active with an excellent pre-Covid exercise tolerance. She developed Covid-19 in mid-2020, reporting an initial mild infection with symptoms including fever, cough, shortness of breath, and loss of taste and smell, which did not require medical assessment or hospitalisation.
After the acute phase she experienced persistent exertional dyspnoea and inability to return to her prior activity levels, severe fatigue, and poor concentration. She was unable to return to work as a nurse due to the severity of her symptoms.
Extensive evaluation approximately three months after the acute illness, including chest x-ray, CT chest, full pulmonary function testing, and cardiac testing with echocardiogram and cardiac MRI, was normal. Based on her persistent, debilitating symptoms she was referred for outpatient pulmonary rehabilitation.
Pre-rehabilitation 6MWT distance demonstrated a walk distance of 320m. Respiratory questionnaires (CAT, SGRQ) and the HADS and PCFS were again consistent with the presence of significant symptoms and impairment in QoL.
As discussed, many patients, even those with initially mild symptoms, will have persistent physical, cognitive, and psychological disability, which impacts upon their QoL and economic productivity following Covid-19 infection. Given the heterogeneity of the persistent symptoms, there is a need for rehabilitation approaches that address these physical and psychological issues in a holistic way. NICE defines rehabilitation as “a set of interventions designed to optimise functioning, health and wellbeing, and reduce disability in people with health conditions in interaction with their environment. In the context of ongoing Covid-19 symptoms, this may include providing information, education, supported self-management, peer support, symptom management strategies, and physical rehabilitation.”2
Comprehensive rehabilitation post- Covid-19 has been recommended by the WHO and interim guidance has been released by the European Respiratory Society (ERS) regarding the role of pulmonary rehabilitation in the condition.4 Initial recommendations were largely extrapolated from data related to the longer-term consequences and rehabilitation needs following the prior SARS and H1N1 outbreaks, and also studies in survivors of acute respiratory distress syndrome (ARDS), supported by the long record of success and safety of pulmonary rehabilitation in chronic lung disease. Now direct evidence supporting the benefits of rehabilitation post-Covid-19 infection is beginning to accumulate.
Pulmonary rehabilitation is a comprehensive intervention of patient-tailored therapies focused on treatable traits including functional, behavioural and emotional traits. It utilises a multidisciplinary approach to guide rehabilitation, including physical, psychological, and psychiatric aspects of management. These programmes have been adapted and tailored for patients recovering from Covid-19 who are often younger and more likely to be in full-time employment versus those living with chronic lung disease attending traditional pulmonary rehabilitation programmes. In addition to careful self-pacing of exercise to avoid post-exertional malaise or exercise-induced symptom flares, many post-Covid-19 rehabilitation programmes focus on teaching self-management skills to assist with fatigue management and neurocognitive symptoms. Psychological support and services to assist with a phased return to work are important components for many patients suffering from protracted symptoms.
On completion of the PRP, the Case 1 patient reported reduced fatigue and overall improved QoL. This was accompanied by a significant improvement in 6MWT test distance to 330m and he no longer required ambulatory oxygen on re-assessment. Additionally, he experienced an improvement in CAT, SGRQ and HADS scores. At six-month follow-up the pulmonary infiltrates on chest x-ray had resolved and PFTs had returned to pre-Covid-19 values.
Similarly, Case 2 demonstrated improvement in 6MWT increasing to 480m following completion of the PRP. She continued to suffer from troublesome fatigue; however, with support and improved self-management skills she was able to manage ongoing fatigue symptoms better and instituted a phased return to work at 50 per cent of her prior hours with a plan to gradually increase frequency and length of shifts as tolerated.
In Ireland, over 1.56 million people have contracted Covid-19 to-date. While the acute illness can be severe, leading to respiratory failure and in some cases death, particularly prior to the widespread availability of effective vaccines, the majority of individuals will experience only mild disease. However, 10-to-30 per cent report persistent symptoms that impact on QoL and productivity, including many individuals who had a mild initial illness. There is an increasing recognition of the large disease burden occurring following acute Covid-19 infection.
Management requires a whole-patient perspective addressing the multi-system condition in a holistic way, with growing evidence supporting a role for comprehensive rehabilitation in the condition. It is not yet known whether more recent variants in circulation, including the Omicron variant which appears to be associated with less severe illness, will also lead to protracted symptoms and impaired QoL. Regardless, it is likely that there will be a continued need for health systems across the world to respond to the aftermath of Covid-19 at least in the medium-term.
DR SARAH O’BEIRNE, Consultant Respiratory Physician, Department of Respiratory Medicine, St Michael’s Hospital, Dun Laoghaire, and St Vincent’s University Hospital, Dublin.
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