Dataset Information

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality.

ABSTRACT: Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the MBL2 gene B variant at codon 54 (rs1800450) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate how the level of serum MBL and the codon 54 variant of MBL (rs1800450) affect the disease severity of COVID-19. A total of 59 patients from the fourth wave and 49 patients from the fifth wave in Japan were analyzed based on serum MBL levels using ELISA and the genotype of MBL2 codon 54 using PCR reaction. There was no significant association between serum MBL levels and age. MBL2 genotype was independent of age, there was no significant difference in different COVID-19 severities, MBL genotypes, and serum MBL levels. Binary logistic regression analysis to identify predisposing factors for severe COVID-19 symptoms demonstrated that patients with the BB genotype had a higher risk of death from COVID-19. Our results quantitatively demonstrated that the BB genotype might be a factor associated with death from COVID-19.

SUBMITTER: Kashiwagi Y

PROVIDER: S-EPMC9961194 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality.

Kashiwagi Yasuyo Y Suzuki Shinji S Takahashi Ryo R Yamanaka Gaku G Hirai Yuji Y Kawashima Hisashi H

Life (Basel, Switzerland) 20230130 2

Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the <i>MBL2</i> gene B variant at codon 54 (<i>rs1800450</i>) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate h ...[more]

PMID: 36836739

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Project description:BackgroundThe SARS-CoV-2 infection triggers excessive immune response resulting in increased levels of pro-inflammatory cytokines, endothelial injury, and intravascular coagulopathy. The complement system (CS) activation participates to this hyperinflammatory response. However, it is still unclear which activation pathways (classical, alternative, or lectin pathway) pilots the effector mechanisms that contribute to critical illness. To better understand the immune correlates of disease severity, we performed an analysis of CS activation pathways and components in samples collected from COVID-19 patients hospitalized in Grenoble Alpes University Hospital between 1 and 30 April 2020 and of their relationship with the clinical outcomes.MethodsWe conducted a retrospective, single-center study cohort in 74 hospitalized patients with RT-PCR-proven COVID-19. The functional activities of classical, alternative, and mannose-binding lectin (MBL) pathways and the antigenic levels of the individual components C1q, C4, C3, C5, Factor B, and MBL were measured in patients' samples during hospital admission. Hierarchical clustering with the Ward method was performed in order to identify clusters of patients with similar characteristics of complement markers. Age was included in the model. Then, the clusters were compared with the patient clinical features: rate of intensive care unit (ICU) admission, corticoid treatment, oxygen requirement, and mortality.ResultsFour clusters were identified according to complement parameters. Among them, two clusters revealed remarkable profiles: in one cluster (n = 15), patients exhibited activation of alternative and lectin pathways and low antigenic levels of MBL, C4, C3, Factor B, and C5 compared to all the other clusters; this cluster had the higher proportion of patients who died (27%) and required oxygen support (80%) or ICU care (53%). In contrast, the second cluster (n = 19) presented inflammatory profile with high classical pathway activity and antigenic levels of complement components; a low proportion of patients required ICU care (26%) and no patient died in this group.ConclusionThese findings argue in favor of prominent activation of the alternative and MBL complement pathways in severe COVID-19, but the spectrum of complement involvement seems to be heterogeneous requiring larger studies.

Dataset Information

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality.

Publications

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality.

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