First, a few updates on items which have popped up over the last few months. One of which, was an observation that countries with anti-tuberculosis vaccination programs (known as “BCG”) seemed to have better COVID-19 stats; but as critics pointed out, while it might be true, there were other factors in play that might explain the observations. A team of researchers took a close look at European countries, where the health records are extensive, and found that the signal was still very much present. They accounted for the potential confounding factors that had been raised by critics of the earlier work. In an earlier blog, I speculated that COVID-19 symptoms, particularly in severe cases, looked strikingly similar to sepsis which is marked by runaway inflammation and clotting (“DIC” – disseminated intravascular coagulation). In browsing around the preprint archives this weekend, a team from Mt Sinai hospital in NYC reported very encouraging results from using anti-coagulation therapy on ventilated patients. The results have been that the death rate halved (in round numbers).

 A Chinese paper reported very preliminary results of using a prototype therapy to interrupt an inflammatory pathway in the “innate” immune system. This is the part of the immune system that is typically the first to encounter pathogens and has a fixed repertoire of templates to recognize pathogens and respond to them. I was impressed by their meticulousness in demonstrating how the “N” (nucleocapsid) protein was able to trigger the innate immune system. What would have been icing on the cake is if they had been able to demonstrate that an existing (well known) compound was able to interrupt the activation process rather than a “biologic” agent. The so-called biologics are produced using genetically engineered bacteria (and sometimes animals) which makes them expensive and tends to lead to a long regulatory review process. In browsing clinical trial registrations, I was happy to see several trials registered for agents such as camostat and ivermectin, which have antiviral properties in vitro, and are known to be well tolerated. What I am not seeing enough of are trials or research papers repurposing existing pharmaceuticals to interrupt (or modulate) inflammatory pathways. There are a few trials using nicotine and drugs for arthritic conditions, but nothing for the “complement pathways” (part of the innate immune system mentioned above).

Our old friend hydroxychloroquine, a wonder drug in its time, has continued to attract colorful operators. It started when a French researcher with a history of questionable research practices announced that he had used it in patients, and it was a game changer. His enthusiastic pronouncements found their way to Fox News and thence to the president for his endorsement. The Lancet and New England Journal of Medicine published high profile papers on hydroxychloroquine (and also ivermectin and angiotensin drugs) that caused the WHO to pause its trials of hydroxychloroquine. In turn, it also elicited a sharp response from researchers around the world about the validity of the data which lead to the papers being retracted.

The data for these papers was supplied by a company called Surgisphere (that no one had heard of) which claimed to have a trove of patient data from hospitals around the world. While the science community focused on the many inconsistencies in Surgisphere’s story, I would argue that the red flag was something very low-tech: the company said it could not allow access to the data due to “non-disclosure agreements”. That was a line used in notorious management studies’ frauds, too. By the way, a recent paper from the UK demonstrated that it is quite possible to run statistical studies on a secure database (the one used for NHS patient records) so that no patient data is disclosed. Yet, the study is auditable. It is unfortunate that hydroxychloroquine has attracted such dubious characters. It was (before resistance) a “wonder” drug for malaria. As far as I can tell, it has no useful role in this pandemic; but that needs to be decided by several (to satisfy the scientific requirement that a result be replicable) properly run trials concluding that it either helps or it doesn’t. Meanwhile, two of the leading medical journals and a couple of co-authors are red-faced victims of their own rush to publish “important” results and burnish their reputations. Hmm, what word also rhymes with “burnish”?