Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Abstract

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

Coinfections with Bacteria, Fungi, and Respiratory Viruses in Patients with SARS-CoV-2: A Systematic Review and Meta-Analysis

“…This might be attributed mainly to the differences in the inclusion criteria and the population age groups included in the studies, or it could be explained by the gender-based biological differences in the host immune response to COVID-19 infection [ 102 ]. The age-dependent defects in T-cell and B-cell function and the excess production of type 2 cytokines could lead to a deficiency in control of viral replication and more prolonged proinflammatory responses, potentially leading to poorer outcomes [ 103 ]. Yet, SARS-CoV-2 patients of any age may develop such coinfections and experience severe disease, especially in those with comorbidities, even in young people [ 4 , 53 ], children [ 27 , 49 ], and infants [ 40 ].…”

Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase

“…Previous studies have shown the relation between haematologic, inflammatory and coagulation parameters with the severity of the disease [ 20 , 21 , 22 , 23 , 24 ], although only a limited number of studies examine the effect of pro-fibrotic and OS markers on the severe clinical course of COVID-19 patients. In this study we analysed, for the first time, the potential value of haematologic, inflammatory and coagulation parameters, together with pro-fibrotic and OS markers as prognostic biomarkers for ARDS development in COVID-19 patients.…”

“…Moreover, the ROC analysis showed that the ability of the AUC of IL-6 to predict disease severity was one of the highest, demonstrating its predictive power for the severity of COVID-19 patients over the course of hospitalisation. In fact, determining the IL-6 level, together with TNF-α, could be considered as a clinical tool for stratifying high-risk patients, and identifying those who should be treated with the IL-6R antagonist tocilizumab [ 21 , 22 , 23 , 24 , 27 , 28 , 29 ]. IL-7, a cytokine with a similar signal transduction pathway to IL-6, may be considered a prognostic marker [ 30 , 31 ].…”

Clinical Predictors of COVID-19 Mortality Among Patients in Intensive Care Units: A Retrospective Study

“…27 The elevated levels of cytokine or hypercytokinemia leads to ARDS along with multiple organ damage. 28 Although an article had corroborated the advantage of using prednisone in COVID-19 patients, 19 utilizing high-dose corticosteroids in critically ill patients is complicated and must be used with extreme care to avoid aggravating complications by worsening laboratory parameters and risk of death. 29,30 Our findings revealed that AKI was an indicator of severe infection and death (OR (95% CI): 7.279 (1.191-65.43), p = 0.032).…”