Update on Innate Immunity in Acute Kidney Injury-Lessons Taken from COVID-19.

The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is above all a consequence of systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage and necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal cells, their cytokine products, complement systems, coagulation cascades and contact systems. Numerous simultaneous pathways of innate immunity should secure an effective host defense. Since they all form a network of cross-linked auto-amplification loops, uncontrolled activation is possible. When the actions of selected pathways amplify, cascade activation evades control and the propagation of inflammation and necrosis worsens, accompanied by complement overactivity and immunothrombosis. The systemic activation of innate immunity reaches the kidney, where the damage affecting single tubular cells spreads through tissue collateral damage and triggers AKI. This review is an attempt to synthetize the connections between innate immunity components engaged in COVID-19-related AKI and to summarize the knowledge on the pathophysiological background of processes responsible for renal damage.

A Case-Control Autopsy Series of Liver Pathology Associated with Novel Coronavirus Disease (COVID-19)

Background: COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a global health emergency. Although well-known for pulmonary injury, COVID-19 is a systemic process. Previous autopsy case series have speculated about, although not clearly defined, patterns of hepatic injury, with steatosis being reported in many patients. This retrospective study is the first case-control study investigating hepatic pathology in a large cohort of deceased COVID-19 patients. Design: Consented autopsy cases at two institutions, between 4/2020 and 2/2021, were retrospectively searched for documentation of COVID-19 as a contributing cause of death. A control group of 40 consecutive consented COVID-19(-) autopsy cases during the same period was identified. The autopsy report and electronic medical records were reviewed for clinical information. H&E-stained liver sections were examined for selected histologic features. Results: 54 COVID-19(+) (mean age 72, M:F=3.2:1) were included in the study. The 40 control cases had a mean age of 64 years and a M:F=1.4:1. The study group was significantly older (p=0.0095) but there was no significant difference in sex. The control group had a higher rate of chronic alcoholism and underlying malignancy, with no difference noted in BMI or other comorbidities. The study group was more likely to have received steroid (72.2% vs. 30%, p<0.0001) and anticoagulation therapy (75.9% vs. 47.5%, p=0.009). Histologically, the study group showed a higher incidence of clinically insignificant steatosis (≤5%), (33.3% vs 12.5%;P = 0.03). Presence of clinically relevant (>5%) steatosis or zonal distribution of steatosis was not significantly different between the groups. Mild nonspecific lobular inflammation and acidophil bodies were also more common in COVID-19 cases (51.9% vs 30.0%;P = 0.04). No significant difference was noted among other histologic features, including vascular changes (Table 1). Conclusions: Mild nonspecific lobular necroinflammatory activity is a common finding in deceased COVID-19 patients, suggestive of COVID-19 hepatitis. COVID-19 is unlikely a cause of clinically significant steatosis. However, patients with COVID-19 are more likely to have low levels of steatosis (≤5%) compared to controls. The high rate of steroid therapy in this population may be a possible source of this minor component of steatosis.

Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19.

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.