Acute COVID-19 and LongCOVID syndrome – molecular implications for therapeutic strategies - review DOI Creative Commons
Katarzyna Michalak,

Alicja Michalak,

Alicja Brenk-Krakowska

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recognized not only for its acute effects but also ability to cause LongCOVID (LCS), a condition characterized by persistent symptoms affecting multiple organ systems. This review examines the molecular and immunological mechanisms underlying LCS, with particular focus on autophagy inhibition, chronic inflammation, oxidative, nitrosative calcium stress, viral persistence autoimmunology. Potential pathophysiological involved in LCS include (1) autoimmune activation, (2) latent persistence, where SARS-CoV-2 continues influence host metabolism, (3) reactivation of pathogens such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV), exacerbating immune metabolic dysregulation, (4) possible inflammatory body fails restore post-infection homeostasis. The manipulation cellular pathways proteins is critical aspect virus’ evade clearance establish long-term dysfunction. Viral NSP13, ORF3a ORF8 have shown disrupt autophagy, thereby impairing promoting evasion. In addition, mitochondrial dysfunction, dysregulated signaling, oxidative HIF-1α activation Nrf2 inhibition create self-sustaining feedback loop that contributes tissue damage symptoms. Therefore understanding basis development effective therapeutic strategies. Targeting glycolysis restoration homeostasis may provide novel strategies mitigate consequences infection. Future research should personalized interventions based dominant perturbations individual patients.

Language: Английский

Understanding chronic inflammation: couplings between cytokines, ROS, NO, Cai2+, HIF-1α, Nrf2 and autophagy DOI Creative Commons
Katarzyna Michalak,

Alicja Michalak

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Chronic inflammation is an important component of many diseases, including autoimmune intracellular infections, dysbiosis and degenerative diseases. An element this state the mainly positive feedback between inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO), increased calcium, hypoxia-inducible factor 1-alpha (HIF-1α) stabilisation mitochondrial oxidative stress, which, under normal conditions, enhance response against pathogens. Autophagy nuclear erythroid 2-related 2 (Nrf2)-mediated antioxidant are negatively coupled with above-mentioned elements to maintain defence at a level appropriate severity infection. The current review first attempt build multidimensional model cellular self-regulation chronic inflammation. It describes feedbacks involved in explains possible pathways by which becomes chronic. multiplicity suggests that symptomatic treatment should focus on inhibiting multiple effectively suppress all dysregulated inflammation, calcium mito-stress other metabolic disturbances.

Language: Английский

Citations

1
Acute COVID-19 and LongCOVID syndrome – molecular implications for therapeutic strategies - review DOI Creative Commons
Katarzyna Michalak,

Alicja Michalak,

Alicja Brenk-Krakowska

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recognized not only for its acute effects but also ability to cause LongCOVID (LCS), a condition characterized by persistent symptoms affecting multiple organ systems. This review examines the molecular and immunological mechanisms underlying LCS, with particular focus on autophagy inhibition, chronic inflammation, oxidative, nitrosative calcium stress, viral persistence autoimmunology. Potential pathophysiological involved in LCS include (1) autoimmune activation, (2) latent persistence, where SARS-CoV-2 continues influence host metabolism, (3) reactivation of pathogens such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV), exacerbating immune metabolic dysregulation, (4) possible inflammatory body fails restore post-infection homeostasis. The manipulation cellular pathways proteins is critical aspect virus’ evade clearance establish long-term dysfunction. Viral NSP13, ORF3a ORF8 have shown disrupt autophagy, thereby impairing promoting evasion. In addition, mitochondrial dysfunction, dysregulated signaling, oxidative HIF-1α activation Nrf2 inhibition create self-sustaining feedback loop that contributes tissue damage symptoms. Therefore understanding basis development effective therapeutic strategies. Targeting glycolysis restoration homeostasis may provide novel strategies mitigate consequences infection. Future research should personalized interventions based dominant perturbations individual patients.

Language: Английский

Citations

0