COVID-19-related headache and innate immune response — a narrative review

Abstract

Headache is one of the most prevalent, although often underreported, symptoms of coronavirus disease 2019 . It is generally accepted that this symptom is a form of secondary headache due to systemic viral infection. There are several hypotheses that try to explain its aetiopathogenesis. One of the most compelling is related to innate immune response to viral infection. This rationale is supported by similarities to other viral infections and the temporal overlap between immunological reactions and headache. Moreover, several key factors in innate immunity have been shown to facilitate headache e.g. interferons, interleukin (IL) -1-β, IL-6, and tumour necrosis factor. There is also a possibility that the virus causes headache by the direct activation of afferents through pattern recognition receptors (i.e. Toll-like receptor 7). Moreover, some data on post-COVID-19 headache and after vaccination against SARS-CoV-2 infection suggests a similar cytokine-mediated pathomechanism in these clinical situations. Future research should look for evidence of causality between particular immune response factors and headache. Identifying key molecules responsible for headache during acute viral infection would be an important step towards managing one of the most prevalent secondary headache disorders.

Headaches and Dizziness as Disabling, Persistent Symptoms in Patients with Long COVID–A National Multicentre Study

“…Straburzyński M et al [ 27 ] analysed the causes of headaches, and their results pointed to an innate immune response with important clinical consequences, which could explain the impact on the daily life of those affected. In line with previous results in the literature, there were significant differences in headaches ( p = 0.031) based on the severity of the dependency status of participants.…”

Hemiplegic Migraine with Concurrent SARS-CoV-2 Infection Leads to Motor Vehicle Collision: a Case Report

“…This molecule activates pathways involving interleukin (IL)-1β, IL-6, tumor necrosis factor, and some chemokines [10]. IL-6 is considered a possible trigger for headache in periods of systemic inflammation given that elevated levels of IL-6 have been seen in patients with chronic and episodic tensiontype headaches [11,12]. Another molecule with a known pivotal role in headache is calcitonin gene-related peptide (CGRP) [13].…”

“…Another molecule with a known pivotal role in headache is calcitonin gene-related peptide (CGRP) [13]. IL-6, in addition to TNF and IL-1β, contributes to increased levels of CGRP and it is postulated that COVID-19-related inflammation may also lead to CGRP release [12].…”

Incidental diagnosis of septo-optic dysplasia in an adult: a case report

“…As in the presented patient, it begins early in the symptomatic phase and is bilateral of a moderate to strong intensity. The frequent phenotypes are migraine or tension-type headache patterns [3,4]. The presented patient reported that the headache during the COVID-19 infection had a different pattern to that of previous ones.…”

“…There was no evidence of meningitic or encephalitic involvement. The pain met the criteria of the International Headache Society for headaches attributed to systemic viral infection [3,4]. The patient experienced head traumas at the ages of 17 and 35.…”