Immunopathogenesis and Immunogenetic Variants in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) continues to spread globally despite the discovery of vaccines. Many people die due to COVID-19 as a result of catastrophic consequences, such as acute respiratory distress syndrome, pulmonary embolism, and disseminated intravascular coagulation caused by a cytokine storm. Immunopathology and immunogenetic research may assist in diagnosing, predicting, and treating severe COVID-19 and the cytokine storm associated with COVID-19. This paper reviews the immunopathogenesis and immunogenetic variants that play a role in COVID-19. Although various immune-related genetic variants have been investigated in relation to severe COVID-19, the NOD-like receptor protein 3 (NLRP3) and interleukin 18 (IL-18) have not been assessed for their potential significance in the clinical outcome. Here, we a) summarize the current understanding of the immunogenetic etiology and pathophysiology of COVID-19 and the associated cytokine storm; and b) construct and analyze protein-protein interaction (PPI) networks (using enrichment and annotation analysis) based on the NLRP3 and IL18 variants and all genes, which were established in severe COVID-19. Our PPI network and enrichment analyses predict a) useful drug targets to prevent the onset of severe COVID-19 including key antiviral pathways such as Toll-Like-Receptor cascades, NOD-like receptor signaling, RIG-induction of interferon (IFN) α/β, and interleukin (IL)-1, IL-6, IL-12, IL-18, and tumor necrosis factor signaling; and b) SARS-CoV-2 innate immune evasion and the participation of MYD88 and MAVS in the pathophysiology of severe COVID-19. The PPI network genetic variants may be used to predict more severe COVID-19 outcomes, thereby opening the door for targeted preventive treatments.

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

“…Finally, it may be hypothesized that COVID-19-associated TRY CAT pathway activation may aggravate the existing disorders in this pathway in comorbid disorders (obesity, dementia, T2DM, hypertension and heart disease, stroke, chronic obstructive pulmonary disease (COPD) and chronic kidney disease) [1][2][3]. Indeed, in all those comorbid diseases, the IDO enzyme is activated as indicated by an increased KYN/TRP ratio [89][90][91][92][93][94][95].…”

Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways

“…The pathogenesis of acute COVID-19 involves the entry of SARS-CoV-2 into host respiratory epithelial cells followed by viral replication and translation in the cytoplasm and infection of adjacent cells of the host cells [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. These processes are accompanied by the activation of immune-inflammatory pathways and, at times, lung injuries, pneumonia, and excessive inflammatory responses, which can progress into disseminated intravascular coagulation and multisystem failure [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

Chronic fatigue, depression and anxiety symptoms in Long COVID are strongly predicted by neuroimmune and neuro-oxidative pathways which are caused by the inflammation during acute infection

“…The immunopathogenesis of the acute infectious phase of COVID-19 comprises activation of the cytokine network with induction of interferons, and interleukin (IL)-1, IL-6, IL-12, IL-18, and tumor necrosis factor (TNF)-α signaling, activation of the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome and as well as activation of key antiviral pathways, Toll-Like-Receptor cascades, NOD-like receptor signaling (Yalcinkaya, Liu et al 2021, Zhao, Di et al 2021, Maes, Tedesco Junior et al 2022, Sagulkoo, Plaimas et al 2022). The NLRP3 is a key component of the innate immune system and an intracellular sensor that is induced by pathogen-associated molecular patterns and damage-associated molecular patterns (Junqueira, Crespo et al 2021, Vora, Lieberman et al 2021).…”