Patients who develop insulin resistance 4-months post-COVID-19 exhibited higher NETosis and miR-21-5p expression than COVID-19 patients without metabolic alterations.

Abstract Post COVID-19 has been associated with alterations in the glucidic metabolism and the presence of metabolic-related microRNAs (miRNAs). Since neutrophils response depends on glycolysis, it is unclear whether the formation of neutrophil extracellular traps (NETosis) is also affected in post COVID-19 patients that developed insulin resistance (IR) post infection. In addition, miR-21-5p has been described as a direct gene regulator of the innate immune response against COVID-19 and the presence of IR. In this study, we evaluated NETosis at 4-months post-COVID-19 and its association with the development of IR and the expression of circulating miR-21-5p. Sixty post-COVID-19 patients were recruited from Víctor-Rios-Ruiz Hospital, and post COVID-19 was evaluated 4-months after acute phase. Serum samples were used to determine biochemical parameters. NETosis was measured in patients at basal condition and in response to TLR agonists using flow cytometry. miR-21-5p expression was measured with RT-qPCR. From our cohort, 19 patients were excluded because of they had IR or type 2 diabetes mellitus before COVID-19, 25 patients developed new IR and 16 remained without glucidic alteration. Our analysis showed that COVID-19 patients with IR-Post-COVID-19 had a significant increment of NETosis in basal condition, reducing the capacity to respond efficiently to TRL3/7/8 agonists. We also found a significant increment of miR-21-5p expression in IR-Post-COVID-19 patients and a significant and positive correlation between miR-21-5p and vital NETosis. These results demonstrated that patients who developed IR post-COVID-19 exhibited higher basal NETosis and higher miR-21-5p expression in comparison with patients without alterations. Supported by grants from PROYECTO COVID1005, ACT210085, Fondecyt Regular 1211480, Instituto de Salud Carlos III (COV20/00110, CP20/00041), Programa de donaciones "estar preparados" UNESPA (Madrid, Spain), Fundación Francisco Soria Melguizo (Madrid, Spain).