Expert Opinion (Violet)
Submitted by Headache Scientific Panel
Authors: Sarah M. Bobker & Matthew S. Robbins
The subject of this article is to provide an insight into the possible mechanism of headache in patients with COVID-19. Specifically:
a. Direct effects of the microorganisms themselves, and activation of several immunoinflammatory mediators (cytokines, glutamate, cyclooxygenase-2/prostaglandin E2 system, nitric oxide system, and reactive oxygen species)
b. More generic indirect mechanisms for headache causality in SARS-CoV2 may exist that are not disease specific, including hypoxia, dehydration, systemic inflammation, and metabolic disturbances.
c. Another important consideration for the mechanism of headache in SARS-CoV2 is related to cytokine release syndrome (CRS). CRS is a supraphysiological response that typically occurs following use of immunotherapy that activates or engages T-cells and/or other immune effector cells, and is often associated with neurotoxicity. In patients with severe SARS-CoV2, higher concentrations of pro-inflammatory cytokines (such as IL-6, IL1B, and IFNγ) have similarly been measured in plasma. The presence of these cytokines is known to result in direct tissue injury and a further inflammatory cascade.