Cytokine and interleukin profile in patients with headache and COVID-19: A pilot, CASE-control, study on 104 patients

Javier Trigo, David García-Azorín, Álvaro Sierra-Mencía, Álvaro Tamayo-Velasco, Pedro Martínez-Paz, Eduardo Tamayo, Angel Luis Guerrero, Hugo Gonzalo-Benito, Javier Trigo, David García-Azorín, Álvaro Sierra-Mencía, Álvaro Tamayo-Velasco, Pedro Martínez-Paz, Eduardo Tamayo, Angel Luis Guerrero, Hugo Gonzalo-Benito

Abstract

Background: The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease.

Methods: An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups.

Results: One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071).

Conclusions: The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.

Keywords: COVID-19; Cytokines; Headache disorders; Immune system; Interleukins.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of median IL-10 levels between COVID-19 patients with and without headache by ANCOVA test, adjusting for age, sex, baseline disability and COVID-19 severity
Fig. 2
Fig. 2
Comparison of median IL-23 levels between COVID-19 patients with and without headache by ANCOVA test, adjusting for age, sex, baseline disability and COVID-19 severity
Fig. 3
Fig. 3
Comparison of median PIGF1 levels between COVID-19 patients with and without headache by ANCOVA test, adjusting for age, sex, baseline disability and COVID-19 severity

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