So, we’ve discussed SARS-CoV-2 ad infinitum. (Or, at least it so feels.)

To remind you of a few facts- these are coronaviruses- so that means the surface of the virus is replete with spikes.   This particular virus’ spikes afford it the ability to bind even more effectively with our cells.  And, since it binds specifically to ACE2 receptors- which regulate our blood pressure (recall many folks with high blood pressure take ACE2 inhibitors)- that means folks with high blood pressure are even more susceptible to virulent attacks.

But we also know that this  virus leaves some of us with virtually no symptoms while it excites horrendous immune responses in others- and it’s that immune response that kills us more than the virus attack.  (I am posting this today, since many of you consider 13 to be unlucky- and this unfortunate over-response  to the coronavirus that I am describing today means those patients are very, very unlucky.)

Well, Dr. Ido Amit (Weissman Institute of Science, Rechovot, Israel) has been studying the immune response for years.   So, it’s not surprising he would be most interested in COVID-19, where a significant portion of those so infected manifest severely overwrought immune responses.  For this study, Amit and his group separated patients that were mildly afflicted by COVID-19 from those who were seriously ill.  The goal was to discern the difference between the two populations.

His group (Drs. Pierre Bost, Amir Giladi, Eyal David, Ronnie Blecher-Gonen, Merav Cohen, Chiara Medaglia, Hanjie Li, and Aleksandra Desckowska [all from Weismann]  Yang Lui and Zheng Zhang [National Clinical Research Center for Infectious Disease, Shenzhen, China] , Benno Schwikowski  and Yanis Bendjelal [Pasteur Institute] , Shuye Zhang [Fudan University, Shanghai, China]) published (actually pre-published) their results in Cell  (Host-viral infection maps reveal signatures of severe COVID-19 patients).

The group was able to examine the different responses by building upon the technique that Dr. Amit has pioneered- single cell genomics.  Individual cells are isolated, their genetic components are amplified, and in so doing the genomes of individual cells can be studied.   By examining the virus-cell interactions at any given moment, it is easier to discern which cells/genes are activated and which ones are silenced.

Interestingly, the cytokine storm [Cyto means cell and kinos means movement] that results from COVID-19 is different than what we might expect.  While the storm renders the patient at risk for multiple system failure, the response is atypical.  Amit’s group found that the virus’ preferred target is epithelial cells.  (In the lungs, these are the cells  involved with respiration- the transport of oxygen from the air to the blood.)

In mild cases of COVID-19, macrophages- the immune cells our body produces to attack infections (which would, in this case, normally be prevailing in the patients’ lungs)- lead the response against the virus.    But, in severe cases, monocytes (blood cells)- instead of the macrophages- effect a cytokine storm.  (Cytokines are teeny proteins, released by a variety of our body’s cells, which coordinate the immune response.  With COVID-19, IL-6 and IL-8, in particular,  have been recruited from our circulatory system to (over)respond to the coronavirus.    In addition to the cytokine storm, our T-cells, as we manifest severe episodes of COVID-19 have been neutralized by the SAR-CoV-2 virus.  This further allows other viruses that we normally are able to counteract to effect additional damage to the body.

Part of the reason some folks manifest a cytokine storm is that the lung’s epithelial cells were already damaged- due to a history of smoking, COPD, or other diseases.

Amit and his group are now planning to develop therapies to protect the macrophages.  In this way, cytokine storms could be averted.

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