Análise de citocinas presentes em tecido placentário associadas à infecção pelo SARS-CoV-2 durante a gestação
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Data
2024-02-20
Autores
Barpp, Patricia Sotter Rodrigues [UNIFESP]
Orientadores
Bonetti, Tatiana Carvalho Souza [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: Durante a pandemia da COVID-19, observou-se que gestantes apresentam maior probabilidade de serem hospitalizadas e necessitar de internação em unidades de terapia intensiva que mulheres não gestantes quando infectadas pelo SARS-Cov-2. Apesar do vírus ter transmissão vertical rara, ele pode infectar células placentária e alterar mecanismos moleculares deste tecido.
Objetivos: Avaliar citocinas presentes em extrato placentário de parturientes infectadas pelo SARS-CoV-2 durante a gestação ou na vigência do parto, comparado com grupo controle sem infecção.
Métodos: Foram incluídas no estudo parturientes assistidas no Departamento de Obstetrícia da EPM-UNIFESP ou Amparo Maternal no período de outubro de 2020 a fevereiro de 2021, que apresentassem infecção pelo SARS-CoV-2 durante a gestação ou no momento do parto. Como grupo controle foram incluídas parturientes sem infecção prévia ou atual pelo SARS- CoV-2. Foram coletadas amostras de tecido placentário, sangue periférico da parturiente e sangue de cordão umbilical. Foi avaliada a presença de anticorpos IgG anti-SARS-CoV-2 em amostras de sangue periférico materno e de cordão umbilical; e a concentração de citocinas (IL-6, IL-8, IL-15, IL-18 e IP-10) em extrato placentário.
Resultados: Gestantes infectadas pelo SARS-CoV-2 em algum momento da gestação ou parto apresentam um aumento de IL-18 comparado ao grupo controle. A concentração de IL- 18 está associada com a presença da infecção, mesmo quando ajustada para tipo de parto e idade gestacional por modelos de regressão linear múltipla. A média de semanas da infecção até o parto foi 15.92±11.21 para as parturientes do grupo COVID-G e 1.22±0.44 para aquelas do grupo COVID-P. Ainda, a maioria dos casos foram assintomáticos-leves em ambos os grupos, COVID-G (80%) e COVID-P (67%). Não houve associação do aumento da IL-18 com o tempo da infecção em relação ao momento do parto (coleta da amostra) ou gravidade dos sintomas.
Conclusões: Ao analisar as concentrações de citocinas em extrato placentário de gestantes infectadas pelo SARS-CoV-2, observamos um aumento significativo da IL-18, e uma elevação menos evidente e não estatisticamente significante das IL-15 e IP-10. Corroborando com a literatura, os resultados deste estudo sugerem que a infecção pelo SARS-CoV-2 gera um perfil inflamatório na placenta das gestantes infectadas, mediado principalmente pela IL-18. Palavras-chave: SARS- COVID-19, citocina, IL-18, gravidez e placenta.
Introduction: During the COVID-19 pandemic, it has been observed that pregnant women infected with SARS-CoV-2 are more likely to be hospitalized and requiring admission to intensive care units than non-pregnant women at the same age. Although vertical transmission is rare, it can infect placental cells and alter the molecular mechanisms of this tissue. Objectives: To evaluate cytokines in placental extract from parturients infected with SARS- CoV-2 during pregnancy or labor, compared to a control group without infection. Methods: The study included parturients assisted in the Obstetrics Department of EPM- UNIFESP or Amparo Maternal from October 2020 to February 2021, who were infected with SARS-CoV-2 during pregnancy or at the time of delivery. The control group included parturients with no previous or current SARS-CoV-2 infection. Placental tissue, peripheral blood and umbilical cord blood samples were collected. We assessed the presence of IgG antibodies in maternal peripheral blood and umbilical cord blood samples; and the concentration of cytokines (IL-6, IL-8, IL-15, IL-18 and IP-10) in placental extract. Results: Pregnant women infected with SARS-CoV-2 during pregnancy or childbirth show increase in IL-18 concentration compared to the control group. The concentration of IL-18 is associated with the presence of infection, even when adjusted for type of delivery and gestational age by multiple linear regression models. The average number of weeks from infection to delivery was 15.92±11.21 for COVID-G group and 1.22±0.44 COVID-P group. Furthermore, most of cases were asymptomatic or mildly symptomatic in both groups (COVID- G, 80% and COVID-P, 67%). There was no association between the increase in IL-18 and the time of infection to the delivery or the severity of symptoms. Conclusions: When analyzing the concentrations of cytokines in placental extract from pregnant women infected with SARS-CoV-2, we observed a significant increase in IL-18, and a less evident and not statistically significant increase in IL-15 and IP-10. Corroborating the literature, the results of this study suggest that SARS-CoV-2 infection produces an inflammatory profile in the placenta, mediated mainly by IL-18.
Introduction: During the COVID-19 pandemic, it has been observed that pregnant women infected with SARS-CoV-2 are more likely to be hospitalized and requiring admission to intensive care units than non-pregnant women at the same age. Although vertical transmission is rare, it can infect placental cells and alter the molecular mechanisms of this tissue. Objectives: To evaluate cytokines in placental extract from parturients infected with SARS- CoV-2 during pregnancy or labor, compared to a control group without infection. Methods: The study included parturients assisted in the Obstetrics Department of EPM- UNIFESP or Amparo Maternal from October 2020 to February 2021, who were infected with SARS-CoV-2 during pregnancy or at the time of delivery. The control group included parturients with no previous or current SARS-CoV-2 infection. Placental tissue, peripheral blood and umbilical cord blood samples were collected. We assessed the presence of IgG antibodies in maternal peripheral blood and umbilical cord blood samples; and the concentration of cytokines (IL-6, IL-8, IL-15, IL-18 and IP-10) in placental extract. Results: Pregnant women infected with SARS-CoV-2 during pregnancy or childbirth show increase in IL-18 concentration compared to the control group. The concentration of IL-18 is associated with the presence of infection, even when adjusted for type of delivery and gestational age by multiple linear regression models. The average number of weeks from infection to delivery was 15.92±11.21 for COVID-G group and 1.22±0.44 COVID-P group. Furthermore, most of cases were asymptomatic or mildly symptomatic in both groups (COVID- G, 80% and COVID-P, 67%). There was no association between the increase in IL-18 and the time of infection to the delivery or the severity of symptoms. Conclusions: When analyzing the concentrations of cytokines in placental extract from pregnant women infected with SARS-CoV-2, we observed a significant increase in IL-18, and a less evident and not statistically significant increase in IL-15 and IP-10. Corroborating the literature, the results of this study suggest that SARS-CoV-2 infection produces an inflammatory profile in the placenta, mediated mainly by IL-18.
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Citação
BARPP, Patricia Sotter Rodrigues. Análise de citocinas presentes em tecido placentário associadas à infecção pelo SARS-CoV-2 durante a gestação. 2024. 69 f. Dissertação (Mestrado em Ginecologia) Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.