COVID-19-associated headache

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D. Syed Musadiq Ali M.B.B.S.[2]

Synonyms and keywords:


The association between COVID-19 and headache was made in 2020. COVID-19 associated headache may be caused by the SARS-CoV-2 virus. There is no established system for the classification of COVID-19 associated headache. The exact pathogenesis of headache in COVID-19 patients is not fully understood. It is thought that headache is the result of cytokine release, direct invasion, metabolic disturbances, inflammation, dehydration, and hypoxia. COVID-19-associated headache must be differentiated from other diseases that cause headache, such as migraine, tension-type headache, cluster headache, seizure, meningitis, encephalitis, neurosyphilis, SAH, subdural hematoma, brain tumor, hypertensive encephalopathy, brain abscess, multiple sclerosis, hemorrhagic stroke, Wernickes encephalopathy, and drug toxicity. A positive history of fever and cough in addition to headache is suggestive of COVID-19-associated headache.

Historical Perspective

  • The association between COVID-19 and headache was made in December, 2019 during the SARS-CoV-2 outbreak initiated in Wuhan, Hubei Province, China.[1]


  • There is no established system for the classification of COVID-19 associated headache.


By Fahimeh Shojaei, M.D. /


Differentiating COVID-19-associated headache from other Diseases

  • For further information about the differential diagnosis, click here.
  • To view the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

Incidence / Prevalence

  • WHO reported that more than 462,801 people have been infected worldwide, more than 380,723 of which are outside of China.[6]
  • The incidence/prevalence of COVID-19-associated headache is still unknown.
  • Guan et al. recently reported 13 percent of COVID-19-associated headache among 1099 laboratory-confirmed cases.


  • There is insufficient information regarding age-specific prevalence or incidence of COVID-19-associated headache.


  • There is insufficient information regarding gender-specific prevalence or incidence of COVID-19-associated headache.


  • There is insufficient information regarding race-specific prevalence or incidence of COVID-19-associated headache.

Risk Factors

  • There are no established risk factors for COVID-19-associated headache.


  • There is insufficient evidence to recommend routine screening for COVID-19 associated headache.

Natural History, Complications, and Prognosis

Natural History



Diagnostic Study of Choice

  • There are no established criteria for the diagnosis of COVID-19-associated headache.

History and Symptoms

  • The hallmark of COVID-19-associated headache is headache.
  • A positive history of fever and cough in addition to headache is suggestive of COVID-19-associated headache.

Common Symptoms

Less Common Symptoms

Physical Examination

Laboratory Findings



  • There are no x-ray findings associated with COVID-19-associated headache.

Echocardiography or Ultrasound

CT scan

  • There are no CT scan findings associated with COVID-19-associated headache.


  • There are no MRI findings associated with COVID-19-associated headache.

Other Imaging Findings

  • There are no other imaging findings associated with COVID-19-associated headache.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with COVID-19-associated headache.


Medical Therapy

  • Medical therapy for COVID-assocaited-headache is still controversial.[7][8][9][10]
  • The use of NSAIDs, who received treatment early in the disease causes worsening of COVID-19 symptoms according to some anecdotal evidences.
  • In March 11, 2020, Fang et al. reported the hypothesis that ibuprofen (40 mg/kg/dose) can increase the risk of developing severe and fatal COVID-19 since ibuprofen is known to upregulate ACE2 receptors.
  • In March 23, 2020, US FDA announced that it is not aware of any evidence that NSAIDs such as ibuprofen could worsen COVID-19.
  • The European Medicines Agency and World Health Organization (WHO) have not yet recommended that NSAIDs be avoided.
  • Despite this recommendation, as a precautionary measure many providers are avoiding NSAIDs in patients with COVID-19.
  • In practice, the decision to continue or stop NSAIDs in patients with COVID-19 is made in collaboration between the treating physician and the patient, after a brief discussion on the limited available evidence.
  • More data are needed before broad recommendations are made.


  • Surgical intervention is not recommended for the management of COVID-19-associated headache.

Primary Prevention

  • There are no established measures for the primary prevention of COVID-19 associated headache.

Secondary Prevention


  1. Meng X, Deng Y, Dai Z, Meng Z (June 2020). "COVID-19 and anosmia: A review based on up-to-date knowledge". Am J Otolaryngol. 41 (5): 102581. doi:10.1016/j.amjoto.2020.102581. PMC 7265845 Check |pmc= value (help). PMID 32563019 Check |pmid= value (help).
  2. Baig, Abdul Mannan; Khaleeq, Areeba; Ali, Usman; Syeda, Hira (2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chemical Neuroscience. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. ISSN 1948-7193.
  3. St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ (August 2004). "Human respiratory coronavirus OC43: genetic stability and neuroinvasion". J. Virol. 78 (16): 8824–34. doi:10.1128/JVI.78.16.8824-8834.2004. PMC 479063. PMID 15280490.
  4. Rossi, Andrea (2008). "Imaging of Acute Disseminated Encephalomyelitis". Neuroimaging Clinics of North America. 18 (1): 149–161. doi:10.1016/j.nic.2007.12.007. ISSN 1052-5149.
  5. St-Jean, Julien R.; Jacomy, Hélène; Desforges, Marc; Vabret, Astrid; Freymuth, François; Talbot, Pierre J. (2004). "Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion". Journal of Virology. 78 (16): 8824–8834. doi:10.1128/JVI.78.16.8824-8834.2004. ISSN 0022-538X.
  6. Tu H, Tu S, Gao S, Shao A, Sheng J (2020). "Current epidemiological and clinical features of COVID-19; a global perspective from China". J Infect. 81 (1): 1–9. doi:10.1016/j.jinf.2020.04.011. PMC 7166041 Check |pmc= value (help). PMID 32315723 Check |pmid= value (help).
  7. Zhang J, Xie B, Hashimoto K (2020). "Current status of potential therapeutic candidates for the COVID-19 crisis". Brain Behav Immun. 87: 59–73. doi:10.1016/j.bbi.2020.04.046. PMC 7175848 Check |pmc= value (help). PMID 32334062 Check |pmid= value (help).
  8. MaassenVanDenBrink A, de Vries T, Danser A (April 2020). "Headache medication and the COVID-19 pandemic". J Headache Pain. 21 (1): 38. doi:10.1186/s10194-020-01106-5. PMC 7183387 Check |pmc= value (help). PMID 32334535 Check |pmid= value (help). Vancouver style error: initials (help)
  9. Fang L, Karakiulakis G, Roth M (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 8 (4):e21. DOI:10.1016/S2213-2600(20)30116-8 PMID: 32171062
  10. FitzGerald GA (2020) Misguided drug advice for COVID-19. Science 367 (6485):1434. DOI:10.1126/science.abb8034 PMID: 32198292

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