Frontiers in immunology · 2026
De novo COVID-19-associated insulin resistance drives dysregulated neutrophil extracellular trap formation (NETosis) four months after infection.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sanhueza Sergio, Cabrera Camilo, Quiroga Romina, Antilef Bárbara, Muñoz Camila, Vera Agustín, Cartes Ricardo, Lamperti Liliana, Guzmán-Gutiérrez Enrique, Aguayo Claudio, Ormazábal Valeska, Hernández Mauricio Alejandro, Lastra Jaime, Riffo Benilde, Cerda Gustavo, Ferrada Luciano, De Gonzalo-Calvo David, García-Hidalgo María C, Henríquez Mario, Barría María Inés, Verdugo Ricardo A, Colombo Alicia, Labarca Gonzalo, Nova-Lamperti Estefanía
Аннотация
BACKGROUND: Glucose metabolism disorders (GMDs) are established risk factors for severe COVID-19, but increasing evidence indicates that they may also develop de novo after SARS-CoV-2 infection. Neutrophil extracellular trap formation (NETosis) plays a central role in immunothrombosis, and because neutrophils rely predominantly on glycolysis, they are particularly sensitive to systemic metabolic disturbances. However, the impact of post-COVID-19 GMDs on NETosis remains poorly understood. This study aimed to characterize the emergence of GMDs after COVID-19 and to determine their effect on neutrophil NETosis.
METHODS: Sixty COVID-19 patients were stratified according to the presence or absence of GMDs before infection and at four months post-infection. Demographic, clinical, metabolic, and inflammatory parameters were assessed. Vital NETosis was quantified by flow cytometry. In addition, the capacity of patient plasma to induce NETosis was evaluated using live-cell imaging of healthy neutrophils as biosensors.
RESULTS: Among patients without pre-existing GMDs, 24 of 36 developed insulin resistance (IR) four months after COVID-19. Neutrophils from these patients exhibited increased basal NETosis but showed impaired NETosis in response to TLR7/8 agonists, key sensors of viral single-stranded RNA, compared with control groups. In contrast, NETosis responses to IL-6 and TNF-α were preserved, excluding an intrinsic neutrophil defect. Plasma from IR patients significantly enhanced NETosis, and in vitro experiments demonstrated that insulin enhances NETosis independently of glucose concentrations.
DISCUSSION: De novo IR following COVID-19 dysregulates NETosis primarily through an insulin-enhancing effect. Post-viral control of glucose metabolism disorders may be critical to limit pathological NETosis and its thrombo-inflammatory consequences.
METHODS: Sixty COVID-19 patients were stratified according to the presence or absence of GMDs before infection and at four months post-infection. Demographic, clinical, metabolic, and inflammatory parameters were assessed. Vital NETosis was quantified by flow cytometry. In addition, the capacity of patient plasma to induce NETosis was evaluated using live-cell imaging of healthy neutrophils as biosensors.
RESULTS: Among patients without pre-existing GMDs, 24 of 36 developed insulin resistance (IR) four months after COVID-19. Neutrophils from these patients exhibited increased basal NETosis but showed impaired NETosis in response to TLR7/8 agonists, key sensors of viral single-stranded RNA, compared with control groups. In contrast, NETosis responses to IL-6 and TNF-α were preserved, excluding an intrinsic neutrophil defect. Plasma from IR patients significantly enhanced NETosis, and in vitro experiments demonstrated that insulin enhances NETosis independently of glucose concentrations.
DISCUSSION: De novo IR following COVID-19 dysregulates NETosis primarily through an insulin-enhancing effect. Post-viral control of glucose metabolism disorders may be critical to limit pathological NETosis and its thrombo-inflammatory consequences.