An interesting article published by Kondratiuk and others in The Lancet Infectious Diseases April 22nd 2021 explores this issue.  

They argue that with more than 122 million cases of COVID-19 reported globally and with a growing second pandemic wave underway, the long term consequences of COVID-19 are in fact an urgent public health priority.  

An international survey of individuals with so called long COVID reported a wide range of symptoms that persisted for months and resulted in substantial disability.  

The latest UK estimates from an unweighted sample of 9063 individuals with
COVID-19 suggested that 22% of individuals still had symptoms some five weeks after initial infection and 10% still had symptoms 12 weeks after infection.  

It has taken a long time for those struggling with long COVID to be heard and they noted that in the United Kingdom a Five Point National Health Service Plan had allocated £10 million to support sufferers of long COVID through specialist clinics and an online rehabilitation service.  

They argue that it is essential that clinicians listen to their patients that understanding and treating long COVID-19 requires an intense, rapid and multidisciplinary research effort.  

One of the challenges to treatment is the absence of a universally recognised case definition. 

It is not known whether long COVID is a novel and distinct syndrome, or multiple, partly overlapping syndromes presenting alone or in combination.

Also how much of this syndrome is accounted for by post intensive care symptoms seen after intensive care admission for non COVID-19 illness, post-viral fatigue syndrome or posttraumatic stress disorder.  

The authors have proposed an overarching conceptual research framework to help define long COVID at the clinical and pathological level and rapidly deliver patient benefit through risk stratified targeting and preventative and therapeutic interventions.  

Current evidence suggests that COVID-19 can have long term effects on multi-body systems including pulmonary, cardiovascular, renal, nervous and also psychiatric effects.  

The most common symptoms of long COVID include fatigue, breathlessness, cough, loss of taste or smell or both, myalgia and gastrointestinal disturbances.  

Persistent symptoms seem more likely to occur after severe disease than after non-severe disease.  

The most pronounced symptoms appear to present with patients who had intensive care treatment. 

However, even individuals with mild COVID-19 reported pronounced symptoms weeks or months after acute disease.  

Persistent symptoms have been associated with evidence of multi-organ disease, even in young, low risk populations.  

Unfortunately, only a small proportion of these symptoms are currently accounted for by pathology.  

The authors argue that understanding the histopathological and pathophysiological cause of the symptoms is a top priority for COVID-19 research.

Conversely, COVID-19 might cause long term organ pathology in the absence of symptoms, for example: 

  • They cite one study which reported abnormal lung function one in four patients three months after leaving hospital.  
  • Reduced diffusion capacity of the lungs was predicted by coagulation markers during the acute phase, suggesting that reduced lung function could be due to underlying vascular pathology.  

However, they found that respiratory symptoms had resolved by this point for most patients in this study.  

Signs of myocardial inflammation on cardiac MRI also persisted for many weeks after acute COVID-19, yet the clinical consequences of this were unclear they argued.  

They argued that physicians should be cautious in the interpretation of any abnormal pathology, suggesting that these findings might be clinically relevant, or could be transient and perhaps even non-specific for COVID-19, reflecting any severe viral illness instead.  

They suggest that the long term sequalae of COVID-19 should be delineated into three distinct categories:  

  1. Persistent symptoms with causal pathological correlates. 
  2. Persistent symptoms without pathophysiological correlates and the causative pathology is unknown.
  3. Organ pathology without associated symptoms or clinical consequence.

They went on to argue that the maximisation of the clinical impact of research into long COVID should be prioritised into two areas.  

The first research priority should be identifying the predictive markers of the long term sequalae of COVID-19 and this should include predictive markers present before infection, for example:

  • Patient age  
  • Pre-existing comorbidities, – during acute illness 
  • Clinical and biochemical markers and – during early convalescence 
  • Functional radiological indicators.  

These markers would allow clinicians to direct interventions to people most at risk of long COVID.  

The second research priority they suggest is to identify clinical intervention through purpose designed studies to reduce the sequalae of COVID-19 with medium and long term clinical outcomes.  

They argue that these interventions should be developed and evaluated for each of the stages of SARS-CoV-2 infection, for example:

  • Pre-infection 
  • Acute illness
  • Early convalescence. 

They suggest that their framework will help to guide future research and enable resources to be targeted efficiently to maximise the delivery of evidence based solutions to the long term effects of COVID-19. 

The London General Practice has brought together leading experts to form a multidisciplinary team to help sufferers with long COVID and offers the service to any patients with long COVID symptoms.  

If you are suffering, please do not hesitate to book an appointment to access this resource. 

Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed

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