Immuno-Pathologic Basis of COVID-19 and the Management of Mild and Moderate Cases
Srijan Goswami, Chiranjeeb Dey in COVID-19 and SARS-CoV-2, 2022
The levels of IL-2, IL-7, IL-10, GSCF, IP-10, MCP1, MIP1a, and TNF-α in the blood of severely ill COVID-19 patients were also elevated. In short, the aberrant release of multiple cytokines appears to trigger a cytokine storm that produces immunopathogenic damage to tissues and organs, even while the immune response seeks to suppress and eradicate the virus (Wiersinga et al., 2020). Thus, it can be mentioned that the cytokine storm involves an immune response that causes collateral damage that may be greater than the immediate benefit of the immune response. Figure 7.5 and Table 7.1 represent specific organs involved and respective signs and symptoms of a systemic cytokine storm. Further studies should be done to find out the detailed pathogenesis of COVID-19 and cytokine storms (Wiersinga et al., 2020; Price et al., 2020; Dutta et al., 2020; Fajgenbaum and June, 2020; WHO, 2020a; Yuki et al., 2020; Kumar and Al Khodor, 2020; Parasher, 2021; Cevik et al., 2020; Abbas et al., 2016; Oliveira et al, 2020).
Overwhelming Post-Splenectomy Infections in the Critical Care Unit
Cheston B. Cunha, Burke A. Cunha in Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
The circulation of splenic IgM memory B-cells significantly decreases after splenic removal [3] and is lower in hyposplenic states [4]. Originating in the spleen’s marginal zone B (MZB), these cells have a low activation threshold and can rapidly respond to T cell-independent antigens such as those that compose the polysaccharide capsule of many pathogenic bacteria. The response facilitates both the innate and adaptive immune responses. In a mouse model, macrophages in the MZB produce a lectin that protects mice from pneumococcemia [5]. Additionally, splenic neutrophil populations also play a role in the eradication of the pneumococcus [6]. Severe infections can be associated with the overproduction of cytokines, resulting in a “cytokine storm,” which can have a detrimental effect. The spleen can act as an anti-inflammatory agent through nicotinic acetylcholine receptors in the spleen, mediated by the CNS’s vagus nerve. The effect is absent in the asplenic mouse [7].
COVID-19
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
While the main target of COVID-19 is the upper respiratory tract with the resultant fever, dry cough, fatigue, and dyspnea, recent evidence has emerged that the endothelial system is the key to many of the more detrimental symptoms.9 The virus enters the alveolar epithelial cells via the ACE-2 receptor and disrupts the cells causing intense inflammation with damage to the significant vascular element of the lungs.9 One of the severe consequences of this unchecked process is a “cytokine storm” resulting in a propagating hyper-inflammatory process that causes extensive ongoing tissue damage.10 A second process that has been identified as a “bradykinin storm” may be equally or more significant.11 The cytokine storm creates extensive damage, while the bradykinin storm induces extensive vascular leakage which allows the virus to get into the circulation and extends the damage throughout the circulatory tree resulting in a series of unusual consequences: blood clots, heart attacks, and strokes (especially in individuals under 50 years of age).12
SARS-COV-2-related immune-inflammatory thyroid disorders: facts and perspectives
Published in Expert Review of Clinical Immunology, 2021
Rosaria Maddalena Ruggeri, Alfredo Campennì, Desiree Deandreis, Massimiliano Siracusa, Renato Tozzoli, Petra Petranović Ovčariček, Luca Giovanella
More severe COVID-19 is associated with an uncontrolled systemic immune and inflammatory response, involving also coagulation and complement systems that is characterized by a strong release of proinflammatory cytokines and results in a systemic hyperinflammatory state leading to multiorgan injury/failure and even death [1,7–9]. This overwhelming immune response is called ‘cytokine release syndrome’ or ‘cytokine storm’, a term that was first used to describe the impressive activation of the immune system that occurs in acute graft-versus-host disease [10]. The cytokine storm is the consequence of an excessive and dysregulated immune response against pathogens and is caused by a massive, rapid release of cytokines into the bloodstream from over-activated immune cells, leading to uncontrolled inflammatory responses [10]. The cytokine storm ultimately leads to extensive apoptosis of epithelial and endothelial cells, vascular leakage, and increased permeability and results in multiple-organ dysfunction [9,11]
The immune dysregulations in COVID-19: Implications for the management of rheumatic diseases
Published in Modern Rheumatology, 2021
Fan Xiao, Man Han, Xiaoxia Zhu, Yuan Tang, Enyu Huang, Hejian Zou, Quan Jiang, Liwei Lu
Although the majority of COVID-19 patients exhibit a good prognosis with mild to moderate symptoms, a subpopulation of critically ill patients with COVID-19 develop acute respiratory distress syndrome (ARDS) and multiple organ injuries, which eventually lead to death [9]. Most of these severe patients showed salient clinical features of cytokine storm, including fever and respiratory failure from ARDS. Laboratory examination revealed substantially higher serum levels of granulocyte colony-stimulating factor, IP-10, MCP-1, macrophage inflammatory protein-1A, and TNF-α in patients requiring intensive care, suggesting an association of cytokine storm with disease severities and poor outcome [9]. Available studies suggest that the excessive production of inflammatory cytokines is closely associated with clinical symptoms and ARDS during COVID-19 development. The overproduction of inflammatory cytokines including IL-6, IL-1β and TNF-α has been shown to contribute to pulmonary injury and extra-pulmonary organ dysfunction, which are also observed in severe COVID-19 patients with clinical signs of multi-organ failures [14].
RSV induced rhabdomyolysis: a case report
Published in Acta Clinica Belgica, 2023
Stijn Arnaert, Thomas Malfait, Astrid Deruyck, Farah Desoete, Maria Nersisjan, Inge Matthijs, Bart Maes
Another possible underlying mechanism could be a maladaptive cytokine release in response to a viral infection. A cytokine storm is a systemic, excessive and uncontrolled inflammation determined by elevated circulating cytokine levels, an acute systemic inflammatory response and secondary organ dysfunction [9]. Interferon-y, interleukin 1,6 and 18, TNF are thought to be the most important proinflammatory cytokines in this immunopathologic process [9]. Downstream signal transduction is mediated by JAK-STAT or MAP pathway. (Figure 2) This causes cell migration (Th1-cells, NK-cells …), production of acute phase proteins, fever and increased protein catabolism [10]. Muscle wasting is observed in healthy animals exposed to proinflammatory cytokines due to an increase in ubiquitine expression and proteasome enzyme activity. Unfortunately, the precise mechanism by which inflammation modulates protein turnover is not yet described [10].
Related Knowledge Centers
- Cytomegalovirus
- Inflammation
- Innate Immune System
- Cytokine
- Multiple Organ Dysfunction Syndrome
- Influenza A Virus Subtype H1N1
- Influenza A Virus Subtype H5N1
- Sars-Cov-1
- Sars-Cov-2
- Epstein–Barr Virus