This is a summary of the NICE guideline relating to:
- new and emerging condition, which has been described using a variety of terms including ’long COVID’,
- this condition can have a significant effect on people’s quality of life
- there is no clinical definition or clear treatment pathway, and there is a minimal, though evolving, evidence base
The clinical case definitions, the term ’long COVID’ is commonly used to describe signs and symptoms that continue or develop after acute COVID-19.
- Three definitions were developed (1):
- acute COVID-19 (0 to 4 weeks),
- ongoing symptomatic COVID-19 (4 to 12 weeks) and
- post-COVID-19 syndrome (12 weeks or longer)
* the Office for National Statistics estimate 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 (2)
NICE guidelines on managing the long term effects of covid-19 and the CDC define long covid patients or covid long haulers as individuals with ongoing symptoms of covid-19 that persist beyond four weeks from initial infection (3).
The panel of UK doctors who contributed to the article by Gorn et al (2) have provided a list of conditions, never experienced before their episodes of acute
COVID-19
Panel: Conditions experienced by members of the UK doctors #longcovid group
- Myocarditis or pericarditis
- Microvascular angina
- Cardiac arrhythmias, including atrial flutter and atrial fibrillation
- Dysautonomia, including postural orthostatic tachycardia syndrome
- Mast cell activation syndrome
- Interstitial lung disease
- Thromboembolic disease (pulmonary emboli or cerebral venous thrombosis)
- Myelopathy, neuropathy, and neurocognitive disorders
- Renal impairment
- New-onset diabetes and thyroiditis
- Hepatitis and abnormal liver enzymes
- New-onset allergies and anaphylaxis
- Dysphonia
Crook et al have described the long term sequalae of covid-19
- (1) in the alveoli of the lungs:
- chronic inflammation
- results in the sustained production of pro-inflammatory cytokines and reactive oxygen species (ROS) which are released into the surrounding tissue and bloodstream
- endothelial damage
- triggers the activation of fibroblasts, which deposit collagen and fibronectin resulting in fibrotic changes
- endothelial injury, complement activation, platelet activation, and platelet-leukocyte interactions, release of pro-inflammatory cytokines, disruption of normal coagulant pathways, and hypoxia
- may result in the development of a prolonged hyperinflammatory and hypercoagulable state, increasing the risk of thrombosis
- (2) in the heart:
- chronic inflammation of cardiomyocytes
- can result in myositis and cause cardiomyocytes death
- dysfunction of the afferent autonomic nervous system
- can cause complications such as postural orthostatic tachycardia syndrome
- prolonged inflammation and cellular damage prompts fibroblasts to secrete extracellular matrix molecules and collagen, resulting in fibrosis
- fibrotic changes are accompanied by an increase in cardiac fibromyoblasts
- damage to desmosomal proteins results in reduced cell-to-cell adhesion
- (3) in the central nervous system:
- long term immune response
- activates glial cells which chronically damage neurons
- hyperinflammatory and hypercoagulable states
- lead to an increased risk of thrombotic events
- blood-brain barrier damage and dysregulation
- results in pathological permeability, allowing blood derived substances and leukocytes to infiltrate the brain parenchyma
- chronic inflammation in the brainstem may cause autonomic dysfunction
- effects of long covid in the brain can lead to cognitive impairment
- (4) possible mechanisms causing post-covid-19 fatigue
- a range of central, peripheral, and psychological factors may cause chronic fatigue in long covid
- chronic inflammation in the brain, as well as at the neuromuscular junctions, may result in long term fatigue
- skeletal muscle
- sarcolemma damage and fiber atrophy and damage may play a role in fatigue
- psychological and social factors may play a role in chronic fatigue in long covid
The PHOSP-COVID Collaborative Group undertook a study investigating recovery 1 year after hospital discharge for COVID-19 (4)
- study (n=2320) reported 29% full recovery at 1 year with female sex, obesity and ventilation associated with being less likely to feel fully recovered at 1 year
- several inflammatory mediators were increased in individuals with the most severe physical, mental health, and cognitive impairments compared with individuals with milder ongoing impairments
Metformin and risk of long COVID
- study evidence showed that there was a 42% relative decrease and 4.3% absolute decrease in the Long Covid incidence occurred in participants who received early outpatient COVID-19 treatment with metformin compared to exact-matching placebo (5)
Reference: