COVID-19-Induced Cytokine Release Syndrome Associated with Pulmonary Vein Thromboses, Atrial Cardiomyopathy, and Arterial Intima Inflammation

Abstract

Coronavirus disease 2019 (COVID-19) is a viral disease induced by severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2), which may cause an acute respiratory distress syndrome (ARDS). First reports have shown that elevated levels of inflammatory cytokines might be involved in the development of organ dysfunction in COVID-19. Here, we can present a case of cytokine release syndrome induced by SARS–CoV-2 causing multiorgan failure and death. Of note, we can report on pulmonary vein thromboses as potential source of cerebrovascular embolic events. Furthermore, we present a specific form of an isolated inflammatory atrial cardiomyopathy encompassing atrial myocardium, perivascular matrix, as well as atrial autonomic nerve ganglia, causing atrial fibrillation, sinus node arrest, as well as atrial clot formation in the right atrial appendage. An associated acute glomerulonephritis caused acute kidney failure. Furthermore, all the described pathologies of organs and vessels were associated with increased local expression of interleukin-6 and monocyte chemoattractant protein-1 (MCP-1). This report provides new evidence about fatal pathologies and summarizes the current knowledge about organ manifestations observed in COVID-19.

The case of complement inhibitors

“…These findings are consistent with histologic examinations of autoptic tissues from COVID-19 cases that confirmed high incidence of venous thromboembolisms ( Lodigiani et al, 2020 ), and microvascular thrombi with endothelial injury and swelling consistent with a thrombotic microangiopathy, in the lungs but also in the heart, liver, small bowel, kidney and other organs ( Goette et al, 2020 ; Varga et al, 2020 ; Pellegrini et al, 2021 ). Such complications have been observed also in pediatric population.…”

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

“…Since macrophages are considered to be the main source of proinflammatory cytokines IL-1β, IL-6, IL-8, IFN-γ and TNF-α, these macrophage-secreted cytokines act on pulmonary vessel ECs, leading to their activation [ 165 ]. This has also been shown on COVID-19 lung autopsies, where alveolar macrophages expressing IL-6 and MCP-1 found in the lung tissues, leading to endothelial damage and necrosis that were evidenced by IL-6 secreting macrophages and ECs adhering to vascular thrombi [ 166 ]. Apart, neutrophils were also reported to drive the coagulatory cascade activation in COVID-19 patients.…”

Unbiased Analysis of Temporal Changes in Immune Serum Markers in Acute COVID-19 Infection With Emphasis on Organ Failure, Anti-Viral Treatment, and Demographic Characteristics

“…The evolution and characteristics of immune system activation are critical for determining the overall clinical outcomes of SARS-Cov-2 infection and other critical care illnesses, as well as the emergence of failure of specific organs (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). For example, it has been observed that lung function deteriorates by the direct cytotoxic effect of the virus and local inflammation governed by monocyte, T cells, and neutrophils during viral sepsis, including SARS-Cov-2 (6,(17)(18)(19). In another example, kidney function impairment in COVID-19 is triggered by vascular dysfunction and monocyte activation, which seemed to have distinct immune characteristics as compared to those seen in other organ failures (12,14,15,17).…”