1 May GI involvement Viral evolution Rendesivir and cats in Wuhan

Fri, 05/01/2020 - 21:05


  1. GI involvement

- In “avant-première” a press release and papers in Science from one of the colleagues in Maastricht (thanks Peter P) , clearly showing that enterocytes various GI models, including organoids, are susceptible to productive SARS-CoV-2 infection, even at low ACE2 expression.  Enterocytes also show a typical antiviral innate response with “interferon-stimulated genes” although type 1 and type 3 IFN themselves are rather low. See the very nice pictures and date in the first two attachments.

- I add also a clinical retrospective study in Zhejiang province, showing that patients who presented with also GI symptoms to the hospital were more ill (higher T°, more sputum, higher inflammation and showed increased family clustering. The authors also investigated whether viruses from these patients were genetically different, but that was not the case.   

  1. With regard to genetic variability: a very didactic explanation (for non-molecular biologists ) in NYT on the genetic evolution of SARS-CoV-2 since its discovery with rather reassuring conclusions:

…. the coronavirus is mutating relatively slowly compared to some other RNA viruses, in part because virus proteins acting as proofreaders are able to fix some mistakes. Each month, a lineage of coronaviruses might acquire only two single-letter mutations

In the future, the coronavirus may pick up some mutations that help it evade our immune systems. But the slow mutation rate of the coronavirus means that these changes will emerge over the course of years. That bodes well for vaccines currently in development for Covid-19. If people get vaccinated in 2021 against the new coronavirus, they may well enjoy a protection that lasts for years.


For more details and nice graphs see: https://www.nytimes.com/interactive/2020/04/30/science/coronavirus-mutations.html?utm_source=Nature+Briefing&utm_campaign=887c6175ad-briefing-dy-20200430&utm_medium=email&utm_term=0_c9dfd39373-887c6175ad-44799709


  1. Preliminary positive news om Remdesivir: “On 29 April, Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID), announced that a clinical trial in more than 1,000 people had showed that those taking remdesivir recovered in 11 days on average, compared with 15 days for those on a placebo.  


See:  https://www.nature.com/articles/d41586-020-01295-8?utm_source=Nature+Briefing&utm_campaign=887c6175ad-briefing-dy-20200430&utm_medium=email&utm_term=0_c9dfd39373-887c6175ad-44799709


Although Fauci compared this results with the first hopeful data on AZT against HIV and with all due respect for one of the greatest scientists I know,  I think we have to be careful since SARS-CoV-2 is, just like Flu, an acute infection, not a chronic one such as HIV and HepB.  In the primate experiments with MERS, it was also clear that Remdesivir was only very effective if given either before or immediately after infection.   

So, let’s wait for the full data before getting euphoric….


  1. Seropositive cats in Wuhan: a short non-peer reviewed paper  (thanks to Peter VL) claims that almost 25 % of cats in Wuhan were serologically positive for antibodies against receptor binding domain of SARS-CoV-2 after the outbreak, including low levels of neutralizing antibodies. There wazs no PCR positive cat and no cross-reactivity with feline coronaviruses.  The highest titers were found in 3 cats of SARS-CoV-2 owners, but most cats with low titers.  Hospital pet cats, but also stray cats had lower levels.  Especially the latter is strange, if you suppose that humans are the source.  So, either cats could catch it from the “environment” (feco-oral?) and/or transmission between cats occurs.


  1. A  reaction in follow-up on the “exit” controversy also by Peter VL:


About the massive testing proposal. I also have the opinion that the current focus on identifying the virus in symptomatic individuals and now contact tracing is the wrong strategy (it seems the Ebola strategy, but we do not deal with Ebola…). But what is proposed in the lancet is also not a good strategy as I do not think it will be possible. I have an opinion somewhere in the middle which I also mentioned on my LinkedIN profile several times already.

We need to start to go back to epidemiology hence, population monitoring, testing for virus (point prevalence) and for antibodies (period prevalence). Having mobile teams that sample randomly 10000-20000 people every day, we might start to see how and where the virus is spreading in the population and in which age groups. Serum tests will tell us if indeed infection is followed by an immune response (or not  or not always) and confirm the spreading of the virus.

Tracking and quantifying virus in waste waters can be added (Frenche paper) so that we monitor transmission and virus accumulation in specific areas as well. By following mobile phone movements (which is done already), we can further link  all this data with population movements….And if needed we can based on all this data, take action, by smaller lockdowsn in certain regions, areas, companies, schools…

As we know the most vulnerable groups (>70 y), we can protect this, but this time we do it right…

In this scenario you can stepwise reduce the lockdown…first people going back to work… etc..