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. 2023 Mar 23:14:1149294.
doi: 10.3389/fneur.2023.1149294. eCollection 2023.

Headache in long COVID as disabling condition: A clinical approach

Arthur Nascimento Rodrigues  1 , Apio Ricardo Nazareth Dias  1 , Alna Carolina Mendes Paranhos  1   2 , Camilla Costa Silva  1 , Thalita da Rocha Bastos  1 , Bárbara Barros de Brito  1 , Nívia Monteiro da Silva  1 , Emanuel de Jesus Soares de Sousa  1 , Juarez Antônio Simões Quaresma  1   2   3 , Luiz Fábio Magno Falcão  1   3
Affiliations

Headache in long COVID as disabling condition: A clinical approach

Arthur Nascimento Rodrigues et al. Front Neurol. .

Abstract

Background and purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can exacerbate previous headache disorders or change the type of pain experienced from headaches. This study aimed to investigate the clinical features of Long COVID headaches.

Method: This was a cross-sectional, descriptive, and analytical observational study that included 102 patients (with previous headache, n = 50; without previous headache, n = 52) with long COVID and headache complaints. The Migraine Disability Assessment Test and Visual Analog Pain Scale were used to collect participants' headache data according to a standardized protocol.

Results: The patients in this study who reported experiencing headaches before COVID-19 had longer headache duration in the long COVID phase than that in the pre-long COVID phase (p = 0.031), exhibited partial improvement in headache symptoms with analgesics (p = 0.045), and had a duration of long COVID of <1 year (p = 0.030). Patients with moderate or severe disability and those classified as having severe headaches in the long COVID phase were highly likely to develop chronic headaches. Hospital admission [odds ratio (OR) = 3.0082; 95% confidence interval (95% CI): 1.10-8.26], back pain (OR = 4.0017; 95% CI: 1.13-14.17), insomnia (OR = 3.1339; 95% CI: 1.39-7.06), and paraesthesia (OR = 2.7600; 95% CI: 1.20-6.33) were associated with headache in these patients.

Conclusion: Headache is a disabling condition in patients with long COVID-19, exacerbating the conditions of those with headaches prior to contracting COVID-19.

Keywords: coronavirus infection; head pain; headache; long COVID-19 syndrome; post-COVID-19.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LD declared a shared affiliation with the authors JQ and LF at the time of review.

Figures

Figure 1
Figure 1
Flowchart of patients who had headache with long-term COVID-19 in the present study. Source: Authors themselves, 2020–2021. †Migraine Disability Assessment. ‡Visual Analog Pain Scale.
Figure 2
Figure 2
(A) Pain intensity according to Visual Analog Pain Scale (VAS) scores in patients with headache and long-term COVID-19. (B) Degree of disability of patients with headache and long-term COVID-19. Source: research protocol. Standard error ≤ 0.05.
Figure 3
Figure 3
Headache prior to COVID-19 is explained by the release of substance P and calcitonin gene related peptide (CGRP) to induce mast cell degranulation and vasodilation, respectively, leading to a proinflammatory state that, when associated with stimulation of sensory ganglia, trigger headache. In long COVID-19 syndrome, stressors and anxiety could lead to changes in neurotransmitters and neurohormonal pathways, triggering brain and vascular changes. In addition, fragments of remaining pathogens may induce the creation of autoantibodies and increase the release of inflammatory cells, such as cytokines and B and T cells, which are associated with the increased production of nitric oxide by inducible nitric oxide synthetase (iNOS). This could lead to a prolonged proinflammatory state, eventually leading to the main post-COVID-19 sequelae. Moreover, disorders of the gut flora can alter the gut-brain axis. All of these factors could contribute to new cases of post-COVID-19 headache and/or worsening of pain in patients with previous headache. Created with BioRender.
See this image and copyright information in PMC

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