Mon, 08/03/2020 - 21:35
- A nice laymen’s overview in “The Healthy” about the 5 presently most promising drugs correctly explains the two phases of COVID (first viral; then inflammatory + pro-coagulator). Whereas Remdesivir and neutralizing monoclonals are directly acting against the virus, dexamethasone and heparin are important in the second phase. And then, there is interferon. But, what is the evidence and the rationale for this good old workhorse?
- Evidence is still limited:
- A non-controlled study in Wuhan suggests that nebulized IFN α2b could be useful in “moderately ill” patients to enhance viral clearance and suppress pro-inflammatory IL-6 and CRP. Results are very difficult to interpret in view of the association with the presumably inactive antiviral arbidol and the differences in age and co-morbidities. I therefore did not discuss this study earlier.
- Recently there is this press release about a beneficial effect of nebulized IFN-β in a reportedly decent controlled trial in 101 patients. They found a much better outcome in the treated group: 79 % less severe disease and twice as likely to complete recovery. Clearly, these data still need to be subjected to peer review.
- Rationale: see the very nice review in “Cell Host & Microbe”: showing how CoV interact with the type I (α and β) and type III (λ) IFN (Fig 1), what the presumed protective and pathogenic role is of these IFN (Fig 2) and how the “mild” type III could be used as prophylaxis and in the late stage, whereas the “stronger” (more pro-inflammatory) type I should be preserved for the early stage (Fig 3).
- More on the origin of SARS-CoV-2:
- A very nice (and complicated) analysis by Boni, Lemey and others in Nature Microbiology with the following conclusion:
“Viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades.
The unsampled diversity descended from the SARS-CoV-2/RaTG13 common ancestor forms a clade of bat sarbecoviruses with generalist properties—with respect to their ability to infect a range of mammalian cells—that facilitated its jump to humans and may do so again.
Although the human ACE2-compatible RBD was very likely to have been present in a bat sarbecovirus lineage that ultimately led to SARS-CoV-2, this RBD sequence has hitherto been
found in only a few pangolin viruses.
Furthermore, the other key feature thought to be instrumental in the ability of SARS-CoV-2
to infect humans—a polybasic cleavage site insertion in the S protein— has not yet been seen in another close bat relative of the SARS-CoV-2 virus.”
Some more explanation (in simpler terms) in the BBC report
- While scientists agree that SARS-CoV-2 is a “natural virus” (see the Nature Medicine paper, I already sent in April), the “conspirators”, led by a reality TV star, called D.J. Trump, keep insisting that it was created in a lab by an evil Chinese scientist, named Shi Zhengli. You can read the summary and a full interview with this prominent lady by the well know John Cohen. Shi agrees with the call for “international collaboration to find the origin”. Apparently a WHO mission is in place: https://www.sciencemag.org/news/2020/07/who-led-mission-may-investigate-pandemic-s-origin-here-are-key-questions-ask
- A number of papers, showing the shift from (too much) emphasis on hand hygiene towards taking the airborne transmission more seriously. Finally, we are starting to wear mouth/nose caps, but still there is not enough attention for the importance of good ventilation in science communication. Why have we become so slow in the West to see the obvious relations and act accordingly? My father, a primary school teacher, always claimed that keeping at least one window open (be it summer or winter time) was important to keep himself and his pupils healthy…
I will be silent for a few days, since I have to prepare a presentation at ITM next week. Putting together all recent progress on vaccines.
Best,
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