Cool stuff, thanks. As you noted, this finding could explain a lot about why convalescent plasma has had such mixed success and why the very pure new antibody cocktails, which wouldn't contain all the other "stuff" from previously infected patients in their plasma, will hopefully be far more effective.
On a perhaps related note, a paper was just published by the Ridgeback/Merck folks on their oral antiviral EIDD-2801/MK-4482 (remdesivir is only IV), showing two key findings. First, they developed a mouse model with supposedly bona fide human lung tissue that duplicates what has been seen with infectivity and impacts of various human coronaviruses, including SARS, MERS and SARS-CoV-2, meaning it should be a good model to test treatments on. And second, they showed that this antiviral is very effective, in vivo, in preventing CV2 infections, used as a pre-exposure prophylactic (and it's worth noting that many of the antivirals were ineffective in vivo, such as HCQ, despite being active in vitro).
The antiviral is in a phase II human study now, which should be rolling into an expanded phase III study soon. Below is the abstract from the paper - where they also talk about inducing a robust type-1 interferon response. Would be curious of your opinion of the paper. This is the drug they brought me back for to help on with process development, as it's all hands on deck to make huge amounts, at risk, in case the clinical trials are positive.
https://assets.researchsquare.com/files/rs-80404/v1_stamped.pdf
Abstract: All known recently emerged human coronaviruses likely originated in bats. Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbor endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained Type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a pre-exposure prophylaxis strategy for coronavirus infection. Our results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment of COVID-19.