Thanks for the news. As always
, I have questions and comments.
Parts of Europe and parts of North America seem to be at or just past peak.
Today's Washington Post reported that at least two people who died Feb. 6 and 17 from Santa Clara, CA (south side of San Francisco Bay) were infected with corona virus. Both died earlier that the previously first reported death on Feb. 29 in Kirkland, WA. These two people had not traveled before becoming ill. These early February deaths suggest that active SARS-CoV-2 infections were in the USA as early as the first week of January 2020.
The Hydroxychloraquine trial has been stopped due to increased mortality. Not only did it not reduce ventilator usage, but increased mortality from 11.4% to 27.8%. I was afraid this would be the case. So you can see why the good Dr Fauci was at odds with president Trump over this. Trump had absolutely no business touting this in the way he did.
I also am not surprised. Do you have a link? If I recall, there was more than one hydroxychloroquine trial.
Skin lesions are showing up. Clotting issues are occurring mostly small vessel but some large. … These seem particularly common in affected children. The lesions look suspiciously like leukoclastic vasculitis to me, which is an immune inflammation of blood vessels. This very likely means many severely affected patients will not make a full recovery and some will be seriously disabled and have shortened life spans.
Are these skin lesions in Covid-19 patients, or those Covid-19 patients who received hydroxychloroquine?
The more we get to see this virus the more serious it looks.
There are now several recent reports linking ACE2 with the product of the gene
TMPRSS2, a transmembrane serine protease enzyme:
Hoffman et al., 2020, Cell 181, 271-280
SARS-CoV-2 Cell Entry Depends on ACE2and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Abstract:
The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option …
This led others to look for cells in respiratory and intestinal tissue that express both ACE2 and TMPRSS2. The authors of the next paper turned to single-cell RNA sequencing, which identifies which of roughly 20,000 genes are “on” in individual cells. They found that only a small percentage of human respiratory and intestinal cells, often well below 10%, make both ACE2 and TMPRSS2. Those cells fall in three types:
- goblet cells in the nose that secrete mucus
- lung cells known as type II pneumocytes that help maintain the alveoli (the sacs where oxygen is taken in)
- one type of so-called enterocytes that line the small intestine and are involved in nutrient absorption.
Ziegler et al., 2020, Cell 181, Pre-proof
SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues
Abstract:
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV-2spike (S)-protein binds ACE2, and inconcert with host proteases, principallyTMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is ahuman interferon-stimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
These results strongly suggest that some respiratory cells are especially vulnerable to coronavirus because they express the two trans-membrane proteins, ACE2 and TMPRSS2. ACE2, a receptor protein, engages with the coronavirus’ spike protein, and TMPRSS2, a protease, cleaves the spike protein, allowing the viral and cellular membranes to fuse. Both ACE2 and TMPRSS2 are expressed more abundantly in certain progenitor cells – cells which normally develop into respiratory tract cells lined with cilia (hair-like projections) that sweep mucus and bacteria out of the lungs.
