Prof. Dr. Jürgen Rockstroh's notes and advice on COVID-19 - Part 4: RESEARCH AND DEVELOPMENT


  • Ana ŠARIĆ
  • Univadis
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Prof. Dr. Jürgen Rockstroh, an infectious disease doctor from the University Hospital in Bonn and current president of The European AIDS Clinical Society is walking us through the current state about COVID-19 R&D

So now let's talk a little bit about research and development and some of the speculations which are out there in the Internet.

Expanded research and publication are welcome with the caveat that results may be disseminated pre-publication or are published without usual peer-review. Clearly, there is ongoing discussion and research around some HIV and other anti-virals which may have some activity against COVID-19. And clearly, the wish and the need for developing drugs is huge, but you can't push things too fast.

Now, the first randomized clinical trial with lopinavir-ritonavir demonstrated no benefit over standard care in 199 hospitalized adults with severe COVID-19. Now, some people argue that potentially the use of anti-virals should only be reserved for the early stage of the disease where antiviral drugs help to decrease viral load. Now, in that particular trial with boosted lopinavir, there was no change in viral load, but there is in vitro data suggesting that there may be some anti-viral activity for this compound, and also for some other protease inhibitors. However, there is also structural analysis demonstrating that there is no darunavir binding to COVID-19 protease, so there is conflicting data.

I think one important message to bring forward at this point is really, at best, we now treat patients within given clinical trials to collect reliable and useable data. The danger of treating patients individually and outside of clinical trials is that we then never can tell because of the lack of a control group or randomized study whether the benefits or negative outcome of a given intervention is related to the drug which was administered, whether this is just the spontaneous disease course development.

A recent case series on hydrochloroquine with or without azithromycin was not able to demonstrate a clear clinical benefit, despite in vitro inhibition of SARS-CoV-2 due to methodological issues. One hospital treated patients, one didn't. So it was not a real randomized trial, and also note that the baseline characteristics of the two groups were completely different, particularly one hospital the patients were much younger, so that obviously has an impact. The same group had postulated infection control benefit of more rapid viral clearance, but there was really a lack of control arm for comparison, and also it was unclear whether this impact on viral load had any impact on clinical outcome. One small randomized clinical trial demonstrated trends for reduced time to clinical recovery and short-term radiological improvement with hydroxychloroquine, though another showed no benefit in terms of viral clearance, clinical radiological endpoints, so really conflicting data with regard to this particular drug regimen. Despite lack of evidence and clearly, indeed no acute viral infection has ever been successfully treated with either product, but the FDA has issued an emergency use authorization to allow hydroxychloroquine and chloroquine products to be used for certain hospitalized patients with COVID-19 while awaiting results from randomized trials. I think clearly if any way possible inclusion to randomized trials at this time is really the preferable strategy.

Further potential drug candidate for treatment COVID-19 is remdesivir, which was originally developed for Ebola therapy. Now, remdesivir is interesting, because it has a broad in vitro antiviral activity against SARS-CoV-2, and there have been some initial reports of COVID-19 patients who have been treated with remdesivir suggesting potential clinical benefit. But, again, these are case reports. Now, fortunately, there are quite a number of clinical trials which are currently ongoing, and so within the next two or three weeks I'm sure we will have first clinical results, which will help us to position remdesivir more reliably at this point.

I think what is important in the context of HIV, there's really no evidence to justify switching the patient from the usual antiviral therapy, and there's really no evidence to support HIV negative patients from taking antivirals outside the context of pre-exposure prophylaxis to prevent HIV acquisition.

Other important things, I think it's important to talk to people who have seen a lot of patients, because you also learn - you learn that some patients who present with cardiovascular disease symptoms, like suspected MI or a stroke, actually come down with COVID infection. So don’t forget that COVID-19 also comes with some other disease manifestations, and there may be cardiac involvement, so also think of COVID in these patients and also talk to people who have experience in doing intensive care therapy, particularly respirator therapy, because it turns out that there are certain things like laying a patient on the belly is important for improving the outcome on the respirator therapy.

I think with regards to drugs and vaccine development, there are many, many things in progress. I think nothing is going to be there for immediate use tomorrow, but I think one of the important messages about containing the epidemic and making sure that our medical systems don’t collapse is clearly one feature, but the other one is obviously that the more we can contain the epidemic, that we will be more readily to have found a successful vaccine intervention or potentially a promising treatment. So keep that in mind, and I hope you all stay healthy.

Thank you.