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Volume 13
Issue 9
10.3390/biomedicines13092128
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Clinical Manifestations and Cytokine Profiles of the Th1, Th2, and Th17 Response Associated with SARS-CoV-2 Omicron Subvariants

by
Matheus Amorim Barreto
1,2,*,
Amanda Mendes Silva Cruz
3,
Delana Melo Volle
3,
Wanderley Dias das Chagas Júnior
3,
Iran Barros Costa
1,2,
Juliana Abreu Lima Nunes
4,
Aline Collares Pinheiro de Sousa
5,
Izabel Keller Moreira Lima
4,
Patrícia Yuri Nogami
1,2,
Iami Raiol Borges
4,
Luany Rafaele da Conceição Cruz
4,
Paula Fabiane da Rocha Nobre
1,2,
Edvaldo Tavares da Penha Junior
4,
Jones Anderson Monteiro Siqueira
3,
Victória Figueiredo Brito do Carmo
4,
Darleise de Souza Oliveira
1,2,
Hugo Reis Resque
3,
Marcos Rogério Menezes da Costa
6,
Rita Catarina Medeiros Sousa
6,
Mirleide Cordeiro dos Santos
3,
Maria Izabel de Jesus
5,
Luana Soares Bargelata
3,
Luciana Damascena da Silva
3 and
Igor Brasil-Costa
1,2,*add Show full author list remove Hide full author list
1
Laboratory of Immunology, Section of Virology, Evandro Chagas Institute, Health and Environment Surveillance Secretariat, Brazilian Ministry of Health, Ananindeua 66093-020, Brazil
2
Latent Cycle Virus Laboratory, Virology Section, Evandro Chagas Institute, Secretariat for Health and Environmental Surveillance, Brazilian Ministry of Health, Ananindeua 66093-020, Brazil
3
Virology Section, Evandro Chagas Institute, Secretariat for Health and Environmental Surveillance, Brazilian Ministry of Health, Ananindeua 66093-020, Brazil
4
Evandro Chagas Institute, Health Ministry of Brazil, Ananindeua 67030-000, Brazil
5
Environment Section, Evandro Chagas Institute, Secretariat for Health and Environmental Surveillance, Brazilian Ministry of Health, Ananindeua 67030-000, Brazil
6
Belém UNIMED Hospital, Belém 66085-823, Brazil
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(9), 2128; https://doi.org/10.3390/biomedicines13092128
Submission received: 16 July 2025 / Revised: 29 August 2025 / Accepted: 29 August 2025 / Published: 31 August 2025
(This article belongs to the Section Immunology and Immunotherapy)
Review Reports Versions Notes

Abstract

Background: The SARS-CoV-2 Omicron variant became the dominant driver during the COVID-19 pandemic due to its high transmissibility and immune escape potential. Although clinical outcomes are generally mild to moderate, the inflammatory mechanisms triggered by Omicron subvariants remain poorly defined. The goal of this study was to consider both viral evolution and the host immune response by assessing plasma cytokine levels in patients infected with SARS-CoV-2 Omicron subvariants. Methods: A total of 115 individuals were recruited, including 40 with laboratory-confirmed SARS-CoV-2 infection by RT-qPCR. Demographic, clinical, and comorbidity data were collected. Plasma levels of IL-6, TNF, IFN-γ, IL-4, IL-2, IL-10, and IL-17A were quantified using Cytometric Bead Array. Subvariant data were obtained from GISAID records and grouped into early (BA.1-lineage) and late (BA.4/BA.5-lineage) Omicron clusters. Statistical analysis included non-parametric and parametric tests, correlation matrices, and multivariate comparisons. Results: Pharyngitis, nasal discharge, cough, and headache were the most common symptoms among infected individuals. Despite no significant variation in symptom distribution across subvariants, infected patients showed higher levels of IFN-γ, TNF, IL-10, IL-4, and IL-2 compared to non-SARS-CoV-2 infected controls (p < 0.05). IL-4 and IL-10 levels were significantly higher in early Omicron infections. No associations were observed between cytokine levels and comorbidities. A significant correlation was found between reporting fewer symptoms and having received three vaccine doses. Conclusions: Infection with Omicron subvariants elicits a strong yet balanced cytokine response. Despite genetic divergence between lineages, immune and clinical patterns remain conserved, with vaccination appearing to mitigate the symptom burden.
Keywords: COVID-19; cytokines; SARS-CoV-2 variants; interleukins COVID-19; cytokines; SARS-CoV-2 variants; interleukins

Share and Cite

MDPI and ACS Style

Barreto, M.A.; Cruz, A.M.S.; Volle, D.M.; Júnior, W.D.d.C.; Costa, I.B.; Nunes, J.A.L.; Sousa, A.C.P.d.; Lima, I.K.M.; Nogami, P.Y.; Borges, I.R.; et al. Clinical Manifestations and Cytokine Profiles of the Th1, Th2, and Th17 Response Associated with SARS-CoV-2 Omicron Subvariants. Biomedicines 2025, 13, 2128. https://doi.org/10.3390/biomedicines13092128

AMA Style

Barreto MA, Cruz AMS, Volle DM, Júnior WDdC, Costa IB, Nunes JAL, Sousa ACPd, Lima IKM, Nogami PY, Borges IR, et al. Clinical Manifestations and Cytokine Profiles of the Th1, Th2, and Th17 Response Associated with SARS-CoV-2 Omicron Subvariants. Biomedicines. 2025; 13(9):2128. https://doi.org/10.3390/biomedicines13092128

Chicago/Turabian Style

Barreto, Matheus Amorim, Amanda Mendes Silva Cruz, Delana Melo Volle, Wanderley Dias das Chagas Júnior, Iran Barros Costa, Juliana Abreu Lima Nunes, Aline Collares Pinheiro de Sousa, Izabel Keller Moreira Lima, Patrícia Yuri Nogami, Iami Raiol Borges, and et al. 2025. "Clinical Manifestations and Cytokine Profiles of the Th1, Th2, and Th17 Response Associated with SARS-CoV-2 Omicron Subvariants" Biomedicines 13, no. 9: 2128. https://doi.org/10.3390/biomedicines13092128

APA Style

Barreto, M. A., Cruz, A. M. S., Volle, D. M., Júnior, W. D. d. C., Costa, I. B., Nunes, J. A. L., Sousa, A. C. P. d., Lima, I. K. M., Nogami, P. Y., Borges, I. R., Cruz, L. R. d. C., Nobre, P. F. d. R., Junior, E. T. d. P., Siqueira, J. A. M., Carmo, V. F. B. d., Oliveira, D. d. S., Resque, H. R., Costa, M. R. M. d., Sousa, R. C. M., ... Brasil-Costa, I. (2025). Clinical Manifestations and Cytokine Profiles of the Th1, Th2, and Th17 Response Associated with SARS-CoV-2 Omicron Subvariants. Biomedicines, 13(9), 2128. https://doi.org/10.3390/biomedicines13092128

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