Iron overload in COVID-19

Sinclair seems to be still interested in Covid-19 and it is not a wonder. I post here 2 papers related to iron overload.
They are written by the same group but you can compare these what Sinclair wrote in "Can Artificial Intelligence Identify Effective COVID-19 Therapies?. This paper is now free to read while when I posted it first it could not yet be seen (https://www.embopress.org/doi/epdf/10.15252/emmm.202012817)

Mitochondria and Microbiota Dysfunction in COVID-19 Pathogenesis, by Saleh J et al

Abstract
The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the "cytokine storm" involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate "cell-free" in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.

Iron: Innocent Bystander or Vicious Culprit in COVID-19 Pathogenesis? Edeas et al

Abstract
The coronavirus 2 (SARS-CoV-2) pandemic is viciously spreading through the continents with rapidly increasing mortality rates. Current management of COVID-19 is based on that respiratory failure is the leading cause of mortality. However, mounting evidence link accelerated pathogenesis in gravely ill COVID-19 patients to a hyper-inflammatory state involving a cytokine storm. Several components of the heightened inflammatory state were addressed as therapeutic targets. Another key component of the heightened inflammatory state is hyper-ferritinemia which reportedly identifies patients with increased mortality risk. In spite of its strong association with mortality, it is not yet clear if hyper-ferritinemia in COVID-19 patients is merely a systemic marker of disease progression, or a key modulator in disease pathogenesis. Here we address implications of a possible role for hyper-ferritinemia, and altered iron homeostasis in COVID-19 pathogenesis, and potential therapeutic targets in this regard.