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

Abstract

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.

Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in Long COVID

“…Previously, we demonstrated that the acute infectious phase of COVID-19 was characterized by increases in physiosomatic and affective symptoms and that a common core could be identified from these domains (Al-Jassas, Al-Hakeim et al 2022). Hence, both acute COVID-19 and long COVID are linked with significant increases in the physio-affective phenome, indicating that comparable pathways may be responsible for the physio-affective phenome of both acute COVID-19 and long COVID.…”

“…As such, our findings indicate that the inflammatory processes during acute COVID-19 and the combination of immune-inflammatory processes (CRP, KYN/TRP and IR) determine to a large extent the physio-affective phenome of Long COVID. Previously, we reported that immune-inflammatory processes (CRP, activation of the NLRP-3 inflammasome, neuro-oxidative pathways), and IR predict the physio-affective phenome of Long COVID (Al-Hadrawi, Al-Rubaye et al 2022, Al-Hakeim, Al-Rubaye et al 2023, Al-Hakeim, Al-Rubaye et al 2023), and that inflammatory processes predict the physio-affective phenome of acute SARS-CoVv-2 infection (Al-Jassas, Al-Hakeim et al 2022). Previously, we have discussed the mechanistic processes that may explain the effects of these different pathways on the onset of physio-affective symptoms, with as major culprits increased neurotoxicity of immune products (including kynurenine), neuro-oxidative stress, and increased IR, and lowered neuroprotection by lowered levels of protective antioxidants and tryptophan (Al-Hadrawi, Al-Rubaye et al 2022, Al-Jassas, Al-Hakeim et al 2022, Al-Hakeim, Al-Rubaye et al 2023, Al-Hakeim, Al-Rubaye et al 2023).…”

Association of IL-10 Gene in Protection Against COVID-19 Disease

“…However, the exact mechanism behind this phenomenon has not been specified yet (3). Although some individuals with COVID-19 might not show symptoms or experience only mild ones, contracting SARS-CoV-2 can result in the development of severe acute respiratory distress syndrome (ARDS), which is characterized by severe pneumonia, damage to the alveoli and, in certain instances, fatalities (4).…”