Association of polymorphisms in long pentraxin 3 and its plasma levels with COVID-19 severity

Abstract

COVID-19 is an infectious respiratory disease caused by SARS-CoV-2. Pentraxin 3 (PTX3) is involved in the activation and regulation of the complement system, demonstrating an important role in the pathogenesis of COVID-19. The aim was to evaluate the association of single nucleotide polymorphisms in PTX3 and its plasma levels with the severity of COVID-19. This is a retrospective cohort study, carried out between August 2020 and July 2021, including patients with confirmed COVID-19 hospitalized in 2 hospitals in the Northeast Region of Brazil. Polymorphisms in PTX3 (rs1840680 and rs2305619) were determined by real-time PCR. PTX3 plasma levels were measured by ELISA. Serum levels of interleukin (IL)-6, IL-8, and IL-10 were determined by flow cytometry. A multivariate logistic regression model was used to identify parameters independently associated with COVID-19 severity. P values < 0.05 were considered significant. The study included 496 patients, classified as moderate ( n = 267) and severe ( n = 229) cases. The PTX3 AA genotype (rs1840680) was independently associated with protection against severe COVID-19 ( P = 0.037; odds ratio = 0.555). PTX3 plasma levels were significantly associated with COVID-19 severity and mortality ( P < 0.05). PTX3 levels were significantly correlated with IL-6, IL-8, IL-10, C-reactive protein, total leukocytes, neutrophil-to-lymphocyte ratio, urea, creatinine, ferritin, length of hospital stay, and higher respiratory rate ( P < 0.05). Our results revealed a protective effect of the PTX3 AA genotype (rs1840680) on the development of severe forms of COVID-19. Additionally, PTX3 plasma levels were associated with the severity of COVID-19. The results of this study provide evidence of an important role of PTX3 in the immunopathology of COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10238-022-00926-w.

The Prognostic Value of Pentraxin-3 in COVID-19 Patients: A Systematic Review and Meta-Analysis of Mortality Incidence

“…The most recent advances, in addition to confirming the previous insights, have highlighted the involvement of PTX3 in the activation and regulation of the complement system while reiterating its important role in the pathogenesis of COVID-19. PTX3 plasma levels were significantly associated with COVID-19 severity and mortality ( p < 0.05) [ 30 ]. The severe group had higher PTX3 levels (median: 987.0 pg/mL) when compared to the moderate group (median: 570.5 pg/mL) ( p = 0.0004) [ 30 ].…”

“…PTX3 plasma levels were significantly associated with COVID-19 severity and mortality ( p < 0.05) [ 30 ]. The severe group had higher PTX3 levels (median: 987.0 pg/mL) when compared to the moderate group (median: 570.5 pg/mL) ( p = 0.0004) [ 30 ]. PTX3 levels at admission were observed to be 3.3 times higher in patients who died than in those who survived (2233 pg/mL [ n = 25] versus 663.2 pg/mL [ n = 144], p < 0.0001) [ 30 ].…”

“…The severe group had higher PTX3 levels (median: 987.0 pg/mL) when compared to the moderate group (median: 570.5 pg/mL) ( p = 0.0004) [ 30 ]. PTX3 levels at admission were observed to be 3.3 times higher in patients who died than in those who survived (2233 pg/mL [ n = 25] versus 663.2 pg/mL [ n = 144], p < 0.0001) [ 30 ]. Moreover, Feitosa et al suggested as PTX3 levels were significantly correlated with IL-6, IL-8, IL-10, CRP, total leukocytes, neutrophil-to-lymphocyte ratio, urea, creatinine, ferritin, length of hospital stay, and higher respiratory rate ( p < 0.05) [ 30 ].…”

“…PTX3 levels at admission were observed to be 3.3 times higher in patients who died than in those who survived (2233 pg/mL [ n = 25] versus 663.2 pg/mL [ n = 144], p < 0.0001) [ 30 ]. Moreover, Feitosa et al suggested as PTX3 levels were significantly correlated with IL-6, IL-8, IL-10, CRP, total leukocytes, neutrophil-to-lymphocyte ratio, urea, creatinine, ferritin, length of hospital stay, and higher respiratory rate ( p < 0.05) [ 30 ]. PTX3 was associated with the risk of patients’ death (per 10 ng/mL, HR 1.08; 95%CI 1.04–1.11; p < 0.001) and in the death/mechanical ventilation ratio (HR 1.04; 95%CI 1.01–1.07; p = 0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer, and CRP as assessed by Lapadula and colleagues [ 36 ].…”

Interleukin-1β Polymorphisms Are Genetic Markers of Susceptibility to Periprosthetic Joint Infection in Total Hip and Knee Arthroplasty

“…Three common single-nucleotide polymorphisms (SNPs) in the PTX3 gene (namely, rs2305619, rs3816527, and rs1840680) have been associated with the concentration of the PTX3 protein in biological fluids (i.e., plasma and BAL [18,19]), the risk of opportunistic infections of bacterial [12,20,21] and fungal [19,22,23] etiology, and the severity of COVID-19 disease [24]. Also, the transcription of PTX3 has been reported to be controlled by two enhancers whose methylation status changes in inflammatory conditions; interestingly, one of them encompasses or is proximal to the three SNPs indicated above, which might explain why these polymorphisms affect the expression of the protein.…”