The study itself is a simple data mining exercise comparing RNA sequencing data collected from lung fluid from six patients in Wuhan suffering from COVID-19 versus 40 "control" samples (originally collected by in 2018 for an unpublished study on asthma and obesity by GlaxoSmithKline). This leads to a number of difficulties in interpreting the differences they found. The control patients are not well matched to the population from which the COVID-19 patients were derived. Furthermore, because the samples from the two groups were prepared by different teams, we cannot rule out that technical differences between how the two groups handled their samples are behind some of the differences that were detected. Usually, one would like to see the key differences that the study observed validated in an independent cohort of patients where COVID-19 and control samples could be processed in parallel, but no such validation was done.
The differences they detect are big enough that they probably don't result from technical artifacts, and the results make sense biologically (people have been
speculating about the role of the Renin-Angiotensin system since the beginning of the pandemic, for example, see discussion in this
PF thread). The paper provides useful information (though this data still needs independent validation), but it should only be seen as advancing a hypothesis rather than providing a definitive answer.
Even if the observations in the paper are correct, there's still the matter of determining cause and effect. The paper establishes only a correlation between COVID-19 infection and activation of bradykinin signaling, but it could be that the elevated bradykinin levels are an effect of the disease rather than a major cause of symptoms. We'd need a lot more data to establish that elevated bradykinin levels are responsible for the more deadly symptoms of COVID-19 (for example, comparing the genes they studied in asymptomatic vs mild vs severe cases of COVID-19 and data showing that drugs targeting these pathways can alleviate symptoms). Of note, people do take drugs for hypertension that affect the Renin-Angiotensin system, and most studies suggest that they do not have any major effects on the course of the disease, which would argue against their hypothesis (though it does not provide definitive evidence against their hypothesis either). Again, a lot more research needs to be done to establish the roles of the RAS and bradykinin in COVID-19.
DrDu said:
Did I miss a passage where they explain what was the role of the supercomputer in creating the Bradikinine hypothesis?
The paper does not seem to mention supercomputing and the methods describe fairly routine RNA-seq methods (over the summer, I taught an undergrad in my lab how to do a similar analysis on a smaller scale). Some groups will submit these jobs to computer clusters run by their university, though I typically do these types of analyses on our own server we have setup in lab (though I'm typically analyzing fewer samples than they did in their paper).
