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 and physiosomatic symptoms. Aims : To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest computed tomography scan anomalies (CCTAs), oxygen saturation (SpO 2 ), 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. 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 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.

Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment

“…Further, self-rated depressive symptoms are positively associated with post-COVID-19 fatigue. A significant association was found between fatigue severity and depressive symptomatology in COVID-19 survivors both during acute disease in 90 patients ( r = 0.71, p < 0.001) [ 34 ] and at 1-year follow-up in 192 patients ( r = 0.56, False Discovery Rate corrected p -value < 0.05) [ 9 ]. Moreover, in a preliminary investigation based on elastic-net penalized regression we found that among a large set of demographic, clinical, and psychopathological predictors only depressive symptomatology significantly predicted the presence of fatigue 6 months after infection in a sample of 122 patients [ 35 ].…”

“…Consistently, Townsend et al in a sample of 128 patients, 10 weeks after initial COVID-19, found a significant association between pre-existing diagnosis of depression and the presence of post-COVID-19 fatigue ( Χ 2 = 5.18, p = 0.02) [ 36 ]. It seems that somewhat independent of the clinical severity of acute COVID-19, depressive psychopathology is associated with persistent fatigue, thus worsening the long-term clinical outcome [ 34 ]. Notably, a recent meta-analysis reported that a significant proportion of COVID-19 survivors showed persistent fatigue and cognitive impairment following resolution of acute COVID-19 [ 37 ].…”

“…Studies scoring ≥ 3 were regarded as low risk of bias, while studies scoring < 3 were regarded as high risk of bias (Table 2 ). The most investigated inflammatory markers were readily available routine biomarkers of inflammation, especially CRP [ 10 , 13 , 26 , 34 , 98 , 110 – 115 ] and neutrophil/lymphocyte ratio (NLR) [ 10 , 13 , 110 , 112 , 114 – 117 ]. Among cytokines, the most investigated were IL-6 [ 34 , 111 – 115 , 118 , 119 ], IL-10 [ 34 , 111 , 112 , 120 ], and TNF-α [ 111 , 112 , 118 , 120 ].…”

“…The most investigated inflammatory markers were readily available routine biomarkers of inflammation, especially CRP [ 10 , 13 , 26 , 34 , 98 , 110 – 115 ] and neutrophil/lymphocyte ratio (NLR) [ 10 , 13 , 110 , 112 , 114 – 117 ]. Among cytokines, the most investigated were IL-6 [ 34 , 111 – 115 , 118 , 119 ], IL-10 [ 34 , 111 , 112 , 120 ], and TNF-α [ 111 , 112 , 118 , 120 ]. Finally, two studies investigated T-cell subpopulations [ 111 , 120 ].…”

“…Finally, two studies investigated T-cell subpopulations [ 111 , 120 ]. Among the included studies, 13 studies [ 10 , 13 , 26 , 34 , 98 , 111 – 113 , 115 – 117 , 119 , 120 ] found a significant association between inflammatory markers and COVID-19-related depressive symptoms, while three studies did not find any statistical association [ 110 , 114 , 118 ]. Specifically, post-COVID-19 depressive symptoms were found to be associated with NLR in four studies [ 112 , 115 – 117 ], with CRP in four studies [ 34 , 98 , 113 , 115 ], with systemic inflammation index (SII) in three studies [ 10 , 13 , 26 ], with the neutrophil count in two studies [ 115 , 117 ], and with IL-6 in two studies [ 34 , 113 ].…”