Pathogenesis and transmission

1. Two papers on pathogenesis:

• Peter Carmeliet’s group proposes that dysfunction of pulmonary vascular endothelial cells has a role in vascular leakage (with edema), a pro-coagulation state (with DIC and raised D-dimers) and recruitment of inflammatory cells (with cytokine storm). There is a very didactic figure on p.2 and the rationale for ongoing clinical trials targeting angiopoietin 2 (a factor that enhances pulmonary edema) and VEGF (that favors vascular permeability) in patients with evidence of a complicated course.  Clearly, this kind of experimental “anti-inflammatory” treatment will never replace the need for a potent antiviral but could be a better option than corticoids.  Remains to be proven (attach 7) 
• A Dutch short “Comment” in Nederlands Tijdschrift voor Geneeskunde (attach 8) summarizes some arguments why “fine dust” could be promoting COVID-19 disease: it can be a carrier for the virus, it upregulates the ACE-2 receptor, induces ciliary dysfuntion, increases epithelial permeability, reduces function of macrophages and T cell responses.  Clearly, hard-hit areas in the worls, including Wuhan, Lombardy, Flanders, Noord-Brabant, NYC are all characterized by finer dust overload, but obviously, there are other elements such as population density.  Studies are  underway to disentangle these elements…

2. Transmission:

• The perspective in Science by Prather et al (attach 9)  emphasizes again the importance of airborne transmission by small (submicrom) particles that will not settle down easily.  The authors call our attention that universal masking in public places, along with widespread testing and efficient tracing has been the key to successful containment of the epidemic in the Far East, as opposed to the insufficient application of those measures in the West. Compare Taiwan and NYC: both 20-25 million inhabitants, but with 1000 X more cases and deaths in NYC.  The authors also provide a list of unknowns that we urgently need to address:
  • minimum virus titer required to cause COVID-19;
  • viral load emitted as a function of droplet size before, during, and after infection;
  • viability of the virus indoors and outdoors;
  • mechanisms of transmission; air-borne concentrations; and spatial patterns.
  • filtering efficiency of different types of masks
• A fascinating paper by Philipp LEMEY (attach 10) shows that early introductions of SAS-CoV-2 in Germany and Washington State in January were effectively ended by vigorous testing, tracing and isolation, but later introductions during February in Italy, Washington and New York City were not and have led to the devastating epidemy in Europe and North-America. I cannot judge on the technical details, but the message is clear: we could have prevented all this misery, by doing the right thing at the right time and that is testing, tracing, isolation.
•  

3. Two “opinions” in Flemish newspapers this weekend confirm what was discussed in the previous paragraphs:

• Hans Snoeck (Columbia) in De Morgen (attach 11)
• Emmanuel André (KULeuven previous “porte parole” of Sciensano) in GVA:  https://www.gva.be/cnt/dmf20200530_04976610/ex-woordvoerder-emmanuel-andre-haalt-zwaar-uit-naar-coronabeleid-experts-hebben-het-risico-niet-gezien

4. 

1. I guess you heard about the mink infections in neighboring Noord-Brabant. Obviously, these animals were infected by humans, but they presumably also spread the disease amongst each other. In tempore non suspect Christian Drosten already proposed that minks (or related captive animals) could be the enigmatic “intermediary host between the bats and the humans, since there are quite a number of these farms in China.  At present, it is all speculation and I’m waiting for more scientific evidence.  But in the meantime, you find in attachment a summary and two original papers on some susceptible species. 

Thus:  

- Several species, including pet dogs and cats, captive lions and tigers, and farmed mink, almost certainly caught the virus from people. 

- Hamsters, rabbits and common marmosets are also susceptible, according to laboratory experiments.

- Experiments in pigs, ducks and chickens show2 that they are not susceptible, but there have been no studies of other livestock animals, such as cows, sheep and horses.

- Cats, ferrets, hamsters1 and horseshoe bats were all able to pass the coronavirus to animals of the same species in the lab, and mink living in close quarters on Dutch farms have passed the infection between them.

Best,

Guido