Post Recovery and Long-Term Effects of the COVID -19: Physiological Insights into Immunological Mechanisms and Future Implications

ABSTRACT

Introduction: Replication and shedding occurs after S. protein binds host cell receptors (ACE-2). Virus propagates in Endoplasmic Golgi Intermediate Compartment (ERGIC). COVID-19 stimulates cellular and humoral immunity. There is decline in CD-4 and CD -8 T-cells and recently role of memory T-cells has been highlighted. Symptoms may persist in COVID-19 patients even after recovery. People with co-existing co-morbidities are at risk of long Covid-19. Aim(s) The present review provides physiological insights into long term effects of COVID-19. Material(s) and Method(s) Articles (2019-2022) were searched from database using MeSH and keywords like "Long COVID" OR "Post recovery effects of COVID" OR "Sequel" "Physiological mechanism" OR "ACE-2 receptors" OR "CORONA VIRUS Sequel" AND "Physiology", AND "Physiological insights" "COVID AND cytokine", "AND", "Physiology" OR "Long COVID" OR "Physiological basis". With inclusion and exclusion criterion and removal of duplicates, selected articles were reviewed. Result(s) Neuropsychiatric symptoms post-recovery were found to be correlated with cytokines IL-2, TN-a, IL-6, IL-1. Imbalance between the inflammatory (IL-1, 6, IFN-g, TNF-a) and anti-inflammatory (IL-10, TGF-a) cytokines are reported. ACE-2 receptors (expressed in GABAnergic and glutamergic neurons) and TMPRSS2 play role in hypoxia, inflammation, thrombosis. Increase APTT, d-dimer and fibrinogen result in coagulation defect and subsequent ischemia in small vessels of brain and lung. Placenta has ACE-2 receptor but varying reports regarding transmission to fetus have been suggested. TNF-a, IFN-g, MCP- 1 and IL-1a plays role in reducing the insulin sensitivity. Monitoring of cytokines would help in assessing the disease progression and even act as therapeutic targets in diseases management. Transcription of the NLRP3 (role in virus elimination) involves NF- eB. Inflammatory cytokines have anti-viral effect by increasing neutrophil recruitment and enhancing adaptive immune response. Treatment strategies include anti-histaminics, naturopathy, probiotics, fibre rich diet and management of the complications which will be discussed in detail in paper. Conclusion(s) Cytokines are implicated in long term effects of COVID-19 in patients post recovery. Understanding of physiological mechanisms is vital to mitigate long term effects. People with co-morbid states are vulnerable to harmful effects and thus need monitoring.