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.

Pulmonary vascular system: A vulnerable target for COVID-19.

The number of coronavirus disease 2019 (COVID-19) cases has been increasing significantly, and the disease has evolved into a global pandemic, posing an unprecedented challenge to the healthcare community. Angiotensin-converting enzyme 2, the binding and entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hosts, is also expressed on pulmonary vascular endothelium; thus, pulmonary vasculature is a potential target in COVID-19. Indeed, pulmonary vascular thickening is observed by early clinical imaging, implying a tropism of SARS-CoV-2 for pulmonary vasculature. Recent studies reported that COVID-19 is associated with vascular endothelial damage and dysfunction along with inflammation, coagulopathy, and microthrombosis; all of these pathologic changes are the hallmarks of pulmonary vascular diseases. Notwithstanding the not fully elucidated effects of COVID-19 on pulmonary vasculature, the vascular endotheliopathy that occurs after infection is attributed to direct infection and indirect damage mainly caused by renin-angiotensin-aldosterone system imbalance, coagulation cascade, oxidative stress, immune dysregulation, and intussusceptive angiogenesis. Degradation of endothelial glycocalyx exposes endothelial cell (EC) surface receptors to the vascular lumen, which renders pulmonary ECs more susceptible to SARS-CoV-2 infection. The present article reviews the potential pulmonary vascular pathophysiology and clinical presentations in COVID-19 to provide a basis for clinicians and scientists, providing insights into the development of therapeutic strategies targeting pulmonary vasculature.