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

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.

Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study

“…However, there is a biological plausibility in an association between fever and headache in COVID-19. While some studies have reported an association between the occurrence of headache and pro-inflammatory substances such as NLRP3, HMGB1, and interleukin 6, [ 2 , 28 ] this has not been the case with all authors [ 21 , 26 , 29 ]. Moreover, a comparison between these studies is difficult because the levels of these substances were measured at different times.…”

Neurological sequelae of COVID-19: a review

“…Furthermore, Caronna and colleagues noted that 50% (14/28) of patients with persistent headaches had no prior history of headache. Nevertheless, the mechanisms for headaches are unknown but proposed to include elevated cytokines and chemokines [ 87 , 89 ], activation of trigeminal nerve branches, and ACE2 interaction in cerebral blood vessels [ 87 ]. Pediatric patients, a population not normally considered with COVID-19, may have neurological sequelae, such as headache and difficulties with concentration, although the evidence is limited [ 90 , 91 ].…”

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?

“…Multiple cytokines were found to be elevated in the blood during acute COVID-19, while increased levels of proinflammatory markers were not detected in the cerebrospinal fluid (CSF) [ 41 ]. Serum levels of IL-4, IL-10, IL-6 and IL1β were elevated in COVID-19 patients [ 33 , 42 , 43 ]. IL-1- and IL-6 are known to trigger neuroinflammation [ 9 ].…”