Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone

Victor Irungu Mwangi; Rebeca Linhares Abreu Netto; Carlos Eduardo Padron de Morais; Arineia Soares Silva; Bernardo Maia Silva; Amanda Barros Lima; Juliana Costa Ferreira Neves; Mayla Gabriela Silva Borba; Fernando Fonseca de Almeida E Val; Anne Cristine Gomes de Almeida; Allyson Guimarães Costa; Vanderson de Souza Sampaio; Luiz Gustavo Gardinassi; Marcus Vinicius Guimarães de Lacerda; Wuelton Marcelo Monteiro; Gisely Cardoso de Melo

doi:10.3389/fimmu.2023.1229611

Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone

Front Immunol. 2023 Aug 16:14:1229611. doi: 10.3389/fimmu.2023.1229611. eCollection 2023.

Authors

Victor Irungu Mwangi¹, Rebeca Linhares Abreu Netto¹, Carlos Eduardo Padron de Morais^{1

2}, Arineia Soares Silva¹, Bernardo Maia Silva^{1

2}, Amanda Barros Lima^{3

4}, Juliana Costa Ferreira Neves¹, Mayla Gabriela Silva Borba^{1

2}, Fernando Fonseca de Almeida E Val^{1

2}, Anne Cristine Gomes de Almeida^{2

5}, Allyson Guimarães Costa^{1

2

3

4

6

7}, Vanderson de Souza Sampaio^{1

2

8}, Luiz Gustavo Gardinassi⁵, Marcus Vinicius Guimarães de Lacerda^{1

2

9}, Wuelton Marcelo Monteiro^{1

2}, Gisely Cardoso de Melo^{1

2

7}

Affiliations

¹ Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil.
² Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil.
³ Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil.
⁴ Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil.
⁵ Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (UFG), Goiânia, Brazil.
⁶ Escola de Enfermagem de Manaus, Universidade Federal do Amazonas (UFAM), Manaus, Brazil.
⁷ Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Universidade do Estado do Amazonas (UEA), Manaus, Brazil.
⁸ Instituto Todos pela Saúde, São Paulo, São Paulo, Brazil.
⁹ Instituto Leônidas & Maria Deane/Fundação Oswaldo Cruz (ILMD/Fiocruz Amazônia), Manaus, Brazil.

Abstract

Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients.

Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array.

Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14.

Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.

Keywords: SARS-CoV-2; biomarkers; cytokine; immune mediators; injury; methylprednisolone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Chemokine CXCL10
Cytokines
HMGB1 Protein*
Humans
Interleukin-10
Interleukin-12
Interleukin-17
Interleukin-2
Interleukin-6
Methylprednisolone / therapeutic use
Myoglobin
SARS-CoV-2

Substances

Cytokines
Interleukin-10
HMGB1 Protein
Interleukin-17
Methylprednisolone
Chemokine CXCL10
Interleukin-2
Interleukin-6
Myoglobin
Interleukin-12

Grants and funding

Financial support was provided by grants from the Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) under the Resolutions # 002/2008, 007/2018, 005/2019 and 005/2022, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior scholarships (CAPES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.