SARS-CoV-2 and Viral Sepsis: Immune Dysfunction and Implications in Kidney Failure

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), first emerged in Wuhan, China. The clinical manifestations of patients infected with COVID-19 include fever, cough, and dyspnea, up to acute respiratory distress syndrome (ARDS) and acute cardiac injury. Thus, a lot of severe patients had to be admitted to intensive care units (ICU). The pathogenic mechanisms of SARS-CoV-2 infection are mediated by the binding of SARS-CoV-2 spikes to the human angiotensin-converting enzyme 2 (ACE-2) receptor. The overexpression of human ACE-2 is associated with the disease severity in SARS-CoV-2 infection, demonstrating that viral entry into cells is a pivotal step. Although the lung is the organ that is most commonly affected by SARS-CoV-2 infection, acute kidney injury (AKI), heart dysfunction and abdominal pain are the most commonly reported co-morbidities of COVID-19. The occurrence of AKI in COVID-19 patients might be explained by several mechanisms that include viral cytopathic effects in renal cells and the host hyperinflammatory response. In addition, kidney dysfunction could exacerbate the inflammatory response started in the lungs and might cause further renal impairment and multi-organ failure. Mounting recent evidence supports the involvement of cardiovascular complications and endothelial dysfunction in COVID-19 syndrome, in addition to respiratory disease. To date, there is no vaccine, and no specific antiviral medicine has been shown to be effective in preventing or treating COVID-19. The removal of pro-inflammatory cytokines and the shutdown of the cytokine storm could ameliorate the clinical outcome in severe COVID-19 cases. Therefore, several interventions that inhibit viral replication and the systemic inflammatory response could modulate the severity of the renal dysfunction and increase the probability of a favorable outcome.

Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation

“…This study further noted that 35.5% patients developed AKI, and 12.3% of them succumbed to death [ 55 ]. Still, the incidence of AKI in SARS-CoV-2infection is lower than in SARS and MERS [ 56 ]. ACE-2 is the main binding site for SARS-CoV-2, and it is expressed in lung tissue and other vital organs, including the kidneys.…”

Construction of an autophagy interaction network based on competitive endogenous RNA reveals the key pathways and central genes of SARS-CoV-2 infection in vivo

“…Strong cytokine storms are widely present in patients with severe COVID-19. The elimination of cytokine storms can improve clinical results, including acute respiratory distress syndrome, acute heart injury and acute renal failure [ 40 , 41 ]. These results indicated that the autophagy interaction network established based on the ceRNA and protein interaction mechanisms may play an important role in the cytokine storm.…”

The evolution and future of diabetic kidney disease research: a bibliometric analysis

“…ACE2 is the receptor for SARS-CoV-2 [29][30][31], which is responsible for the COVID-19 outbreak, giving rise to the following two questions: will renal injury be increased in COVID-19 patients with diabetes and will ACEi/ARB treatment have an impact on the renal outcome of COVID-19 patients with diabetes? COVID-19 patients with T2DM have higher acute kidney injury prevalence rates than individuals without diabetes [32], which may be explained by ACE2-mediated viral cytopathic effects [26,33]. Some studies [34,35] implied that RAAS inhibitors increased the risk of acute kidney injury, suggesting more concern about renal outcomes in patients with severe COVID-19 with diabetes who are treated with…”