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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s10194-021-01268-w.

Related collections

Most cited references 41

Record: found
Abstract: found
Article: found

COVID-19: consider cytokine storm syndromes and immunosuppression

Puja Mehta, Daniel McAuley, Michael Brown … (2020)

As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).

0 comments Cited 4819 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

(2018)

0 comments Cited 1391 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

Jonathan A. C. Sterne, Srinivas Murthy, Janet V. Diaz … (2021)

Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.

0 comments Cited 1178 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Pedro Martínez-Paz:

ORCID: http://orcid.org/0000-0002-5772-8153

pedrojose.martinez@uva.es

Journal

Journal ID (nlm-ta): J Headache Pain

Journal ID (iso-abbrev): J Headache Pain

Title: The Journal of Headache and Pain

Publisher: Springer Milan (Milan )

ISSN (Print): 1129-2369

ISSN (Electronic): 1129-2377

Publication date (Electronic): 4 June 2021

Publication date PMC-release: 4 June 2021

Publication date Collection: 2021

Volume: 22

Issue: 1

Electronic Location Identifier: 51

Affiliations

[1 ]GRID grid.411057.6, ISNI 0000 0000 9274 367X, Headache Unit, Neurology Service, , University Clinical Hospital of Valladolid, ; 3 Ramón y Cajal Ave, 47003 Valladolid, Spain

[2 ]GRID grid.411057.6, ISNI 0000 0000 9274 367X, Haematology and Haemotherapy Service, , University Clinical Hospital of Valladolid, ; 3 Ramón y Cajal Ave, 47003 Valladolid, Spain

[3 ]GRID grid.5239.d, ISNI 0000 0001 2286 5329, Department of Surgery, Faculty of Medicine, , University of Valladolid, ; 7 Ramón y Cajal Ave, 47005 Valladolid, Spain

[4 ]GRID grid.411057.6, ISNI 0000 0000 9274 367X, Anaesthesiology and Resuscitation Service, , University Clinical Hospital of Valladolid, ; 3 Ramón y Cajal Ave, 47003 Valladolid, Spain

[5 ]GRID grid.5239.d, ISNI 0000 0001 2286 5329, Department of Medicine, Dermatology and Toxicology, Faculty of Medicine, , University of Valladolid, ; 7 Ramón y Cajal Ave, 47005 Valladolid, Spain

[6 ]Institute of Health Sciences of Castile and Leon (ICSCYL), Santa Clara Square, 42002 Soria, Spain

Author information

Pedro Martínez-Paz http://orcid.org/0000-0002-5772-8153

Article

Publisher ID: 1268

DOI: 10.1186/s10194-021-01268-w

PMC ID: 8177251

PubMed ID: 34088273

SO-VID: a57b2594-bd51-4308-aefc-b88f7fed8ad3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.