Increased insulin resistance due to long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection

Background. Some months after the remission of acute COVID-19 infection, some people show depressive symptoms, which are predicted by increased peak body temperature (PBT) and lowered blood oxygen saturation (SpO2). Nevertheless, no data indicate whether Long COVID is associated with increased insulin resistance (IR) in association with depressive symptoms and immune, oxidative, and nitrosative (IO&NS) processes. Methods. We used the homeostasis Model Assessment 2 (HOMA2) calculator to compute beta-cell function, insulin sensitivity and resistance (HOMA2-IR) and measured the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HAMD) in 86 Long COVID patients and 39 controls. We examined the associations between the HOMA2 indices and PBT and SpO2 during acute infection, and depression, IO&NS biomarkers (C-reactive protein, NLRP3 activation, myeloperoxidase, and advanced oxidation protein products) 3-4 months after the acute infection. Results. Long COVID is accompanied by increased HOMA2-IR, fasting blood glucose, and insulin levels. We found that 33.7% of the patients versus 0% of the controls had HOMA2-IR values >1.8, suggesting IR. PBT, but not SpO2, during acute infection significantly predicted IR, albeit with a small effect size. Increased IR was significantly associated with depressive symptoms as assessed with the BDI and HAMD above and beyond the effects of IO&NS pathways. There were no significant associations between increased IR and the activated IO&NS pathways during Long COVID. Conclusion. Long COVID is associated with new-onset IR in a subset of patients. Increased IR may contribute to the onset of depressive symptoms due to Long COVID by enhancing overall neurotoxicity.