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.

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB, and Wnt/β-Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

“…Heatmaps were produced using Appyter and MetaScape. Functional enrichments were established using the Gene Ontology (GO) biological processes, the GO molecular functions and the GO cellular components, STRING local network clusters, the KEGG pathways, Reactome pathways (the European Bioinformatics Institute Pathway Database) 10 , PANTHER biological processes (PANTHER-Gene List Analysis) 11 , TTRUST transcriptional regulatory relationships, InterPro domains (InterPro) 12 , Wikipathways (WikiPathways -WikiPathways), and DOID annotations of human diseases (Disease Ontology-Institute for Genome Sciences, University of Maryland) 13 . We also performed Molecular Complex Detection (MCODE) (using Metascape) to delineate small molecular complexes.…”

“…However, even CFS and ME, which are not secondary to any medical disorder, show a high comorbidity with symptoms of irritable bowel syndrome and depression (7), while CFAS-D symptoms are hallmarks of autoimmune, infectious, immune system, and psychiatric disorders, including major depression and schizophrenia and many more medical conditions (1,3,(7)(8)(9)(10). CFAS-D symptoms are reflective manifestation of the symptomatome of, for example, coronavirus disease 2019 (COVID- 19), chronic kidney disease with hemodialysis, schizophrenia, and rheumatoid arthritis (9)(10)(11)(12)(13)(14), suggesting that CFAS-D symptoms are part of the core of these medical disorders and not the result of some "it is in the mind" process, if there would exist such a process.…”

Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB and Wnt/Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis andChronic Fatigue Syndrome: A Review and New Hypothesis Based on Results of Network, Enrichment and Annotation Analyses

“…However, even CFS and ME, which are not secondary to any medical disorder, show a high comorbidity with symptoms of irritable bowel syndrome and depression [7], while CFAS-D symptoms are hallmarks of autoimmune, infectious, immune system and psychiatric disorders, including major depression and schizophrenia, and many more medical conditions [1,3,[7][8][9][10]. CFAS-D symptoms are reflective manifestation of the symptomatome of for example COVID-19, chronic kidney disease with hemodialysis, schizophrenia, and rheumatoid arthritis [9,[10][11][12][13][14], suggesting that CFAS-D symptoms are part of the core of these medical disorders and not the result of some "it is in the mind" process, if there would exist such a process.…”