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Content summary

How is headache associated with COVID-19?

  • COVID-19 is the disease caused by the SARS-2 virus.
  • People with COVID-19 have reported a wide range of symptoms, ranging from mild to severe.
  • Symptoms typically appear 2 to 14 days after exposure to the virus and patients may present with a cough, shortness of breath or difficulty breathing alongside a fever, chills, muscle pains, sore throat, new loss of smell or taste, or headache.
  • Headache is one of the main clinical characteristics of patients with COVID-19, with an estimated prevalence of 74.4% in patients administered to the Vall d-Hebron hospital in Barcelona, Spain.
  • The characteristics of headache associated with COVID-19 differ according to time of onset during the evolution of the disease, showing more migraine-like symptoms at the asymptomatic stage.

Why is headache a symptom of COVID-19?

  • The SARS-2 virus infects the body via the angiotensin-converting enzyme 2 (ACE2) receptor, which is present throughout the human body.
  • The virus enters the body through the nasal cavity and causes initial neuroinflammation.
  • It can then travel into the lungs, causing pneumonia before entering the bloodstream causing systemic inflammation through a cytokine storm.
  • When the patient develops acute respiratory syndrome, it leads to increased permeability of the blood-brain barrier leading to direct infection of the microglia and endothelialitis.
  • The virus may then directly infect the central nervous system (CNS), attacking the trigeminal and olfactory nerve, triggering activation of the trigeminal vascular system. This potentiates the neuroinflammation at a localised level in the CNS.
  • Levels of interleukin 6 (IL-6), that is a known pro-inflammatory cytokine released during migraine attacks, were lower and more stable in COVID-19 patients with headaches than those without.

How does headache evolve in COVID-19?

  • There are potentially four pathways through which COVID-19 evolves; (i) 30% of patients present with no symptoms and acquire immunity, (ii) 55% of patients have mild symptoms and then go on to develop immunity, (iii) 10% develop severe symptoms which require hospitalisation, and (iv) 5% require admission to ICU.
  • The type of headache patients experience depends on when in the disease timeline symptoms first present.
  • Up to a third of patients develop a reoccurring, difficult-to-treat, ongoing headache which appears to be a new persistent daily headache.
  • Headache is a predictive symptom of COVID-19 evolution—patients with a headache generally experience shorter disease duration by approximately seven days, and those patients with a headache plus anosmia are hospitalised for a shorter duration (minus seven days).

How can we treat headache associated with COVID-19?

  • Ibuprofen is safe for patients to take during the COVID-19 pandemic.
  • There was initial clinician concern regarding the use of candesartan, but this is an ACE-1 inhibitor, not ACE-2.
  • Calcitonin gene-related peptide (CGRP)-monoclonal antibodies are also currently considered safe to use during this time as they do not suppress the immune system.
  • CGRP is one of the main neuroinflammatory molecules, and there is a clinical trial underway evaluating the efficacy of vazegepant for hospitalised patients with COVID-19.