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Long covid

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

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

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)


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