Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety and chronic fatigue syndrome-like symptoms due to COVID-19: a nomothetic network approach

Abstract

Background: COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like physiosomatic (previously known as psychosomatic) symptoms. Aims: To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest CT-scan anomalies (CCTAs), oxygen saturation (SpO2), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs). Method: The above biomarkers were assessed in 60 COVID-19 patients and 30 heathy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales. Results: Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors. Moreover, one common infection-immune-inflammatory (III) core underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms. Discussion: Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which both may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection.

Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study

“…We calculated a single pure physiosom FF subdomain score as: muscular pain + muscle tension + fatigue + autonomous symptoms + gastrointestinal symptoms + headache + a flu-like malaise (thus excluding the cognitive and affective symptoms). To construct a composite score reflecting the severity of the physio-affective phenome, we extracted the first factor from the pure FF and pure and physiosom HAMA and HAMD scores, which reflect the physio-affective phenome 25, 26 . Additionally, we constructed z unit-based composite scores indicating autonomic symptoms, sleep problems, fatigue, gastro-intestinal symptoms, and cognitive symptoms using all relevant HAMD, HAMA, and FF items (z transformed).…”

“…Recently, we reported that not only the acute infectious phase 25 but also Long COVID 26 is characterized by concurrent elevations in key depression (depressed mood, feelings of guilt, suicidal ideation, loss of interest), key anxiety (anxious mood, tension, fears, anxiety behavior at interview), chronic fatigue and physiosomatic symptoms including autonomic and gastrointestinal (GIS) symptoms, malaise and muscle pain. Additionally, in both the acute phase and Long COVID, a single latent vector could be derived from these physiosomatic and affective symptoms, demonstrating that these symptom profiles are the expression of a shared core, namely the COVID-19 and Long COVID “physio-affective phenome” 25, 26 .…”

“…We reported that in acute COVID-19, the physio-affective phenome was largely predicted by a latent factor derived from indicants of increased proinflammatory and immunoregulatory cytokines, chest computerized tomography scan abnormalities (CCTAs), including ground-glass opacities, crazy patterns and consolidation and lower oxygen saturation in peripheral blood (SpO2) 25 . Importantly, lowered SpO2 and increased peak body temperature during the acute phase of illness largely predict the severity of the physio-affective phenome of Long COVID 26 .…”

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

“…Elevated XA levels may cause severe neuronal damage, apoptosis, mitochondrial dysfunctions, disrupt glutamate transmission, and impair presynaptic transmission caused by NMDAR stimulation (Kanchanatawan, Sirivichayakul et al 2018). Such effects may contribute to the development of neuropsychiatric disorders such as depression, anxiety and chronic fatigue due to COVID-19 (Al-Jassas, Al-Hakeim et al 2022). Indeed, TRYCATs are confirmed to be associated with various mental disorders, including depression, and anxiety (Maes, Mihaylova et al 2007, Maes, Leonard et al 2011), somatization and chronic fatigue syndrome (Maes and Rief 2012), cognitive impairments (Kanchanatawan, Hemrungrojn et al 2018), and psychosis (Almulla, Vasupanrajit et al 2021).…”

“…Moreover, some TRYCATs, namely KYN, KA and 3HK are associated with musculoskeletal injuries due to their agonistic effects on the AhR (Duan and Lu 2019, Al Saedi, Sharma et al 2020, Eisa, Reddy et al 2020, Kondrikov, Elmansi et al 2020). Thus, increased TRYCAT levels could exacerbate the neuro-immune and neuro-oxidative toxicity caused by increased oxidative stress and M1 and Th-1 activation resulting in comorbid affective disorders (Al-Jassas, Al-Hakeim et al 2022). Therefore, it is safe to hypothesize that the accumulation of TRYCATs in SARS-CoV2 infected patients may play a role in the neuropsychiatric and cognitive syndromes of long or post-COVID syndrome (Taquet, Geddes et al 2021).…”