Severe COVID-19 and Sepsis: Immune Pathogenesis and Laboratory Markers

Abstract

The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has taken a significant toll on people and countries all over the world. The pathogenesis of COVID-19 has not been completely elucidated yet. This includes the interplay between inflammation and coagulation which needs further investigation. The massive production of proinflammatory cytokines and chemokines results in the so-called cytokine storm, leading to plasma leakage, vascular hyperpermeability, and disseminated vascular coagulation. This is usually accompanied by multiorgan failure. The extensive changes in the serum levels of cytokines are thought to play a crucial role in the COVID-19 pathogenesis. Additionally, the viral load and host inflammation factors are believed to have a significant role in host damage, particularly lung damage, from SARS-CoV-2. Interestingly, patients exhibit quantitative and qualitative differences in their immune responses to the virus, which can impact the clinical manifestation and outcomes of COVID-19. There needs to be a better understanding of the dynamic events that involve immune responses, inflammatory reactions, and viral replication in the context of the COVID-19 infection. Here, we discuss the main aspects of COVID-19 pathogenesis while supporting the hypothesis that inflammatory immune responses are involved in the progression of the disease to a more critical and fatal phase. We also explore the similarities and differences between severe COVID-19 and sepsis. A deeper understanding of the COVID-19 clinical picture as it relates to better-known conditions such as sepsis can provide useful clues for the management, prevention, and therapy of the disease.

The Role of High-Density Lipoprotein in COVID-19

“…The most striking pathophysiological feature of patients with severe COVID-19 is a dysregulated immune response, characterized by lymphopenia and a cytokine storm, which results in acute respiratory distress syndrome, hepatic dysfunction, multiple-organ failure, and ultimately death. Abnormal coagulation function is also a prominent feature in severe COVID-19 cases (Beltrán-García et al, 2020;José et al, 2020;Song et al, 2020;Zafer et al, 2021).…”

The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells

“…When infected with live SARS-CoV-2, K18-hACE2 mice exhibit sex-and timedependent symptomatology and 100% lethality [5][6][7]. COVID-19 patients develop a "cytokine storm" and a sepsis-like condition [8,9]; the contribution of surface elements to the activation of these inflammatory pathways remains unknown. SP mediates SARS-CoV-2 cell entry by binding to the plasmalemmal ACE2 receptor.…”

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

“…Pneumonia usually occurs after 10–20 days of the symptomatic infection, which is associated with reduced oxygen saturation, blood gas deviations, and discrete changes in the appearance of the lungs in chest radiographs. Different hematological and inflammatory biomarkers, including lymphopenia, the elevation of C-reactive protein, and pro-inflammatory cytokines, have been used as diagnostic laboratory markers for the diagnosis of COVID-19 [ 13 ]. Although SARS-CoV-2 typically causes upper respiratory tract infections, the virus may spread to other tissues such as the central nervous system, cardiovascular system, gastrointestinal system, liver, and kidney, causing damage to those tissues and organs [ 14 , 15 ].…”