A lot of respect for @DrAseemMalhotra , but this is promoting frankly dangerous advice on very shaky ground. Do not stop or change your statin dose without consulting your own doctor and beware medicines advice without proper clinical evidence... Thread follows https://twitter.com/DrAseemMalhotra/status/1247762398049472512

The link between low blood LDL levels and poor infection outcomes is well recognised, as shown here where compared to those with high cholesterol, those with lower levels had higher risks of sepsis

And yes, LDL is a carrier molecule for bacterial toxins that are cleared by the liver when LDL engages it's receptor on hepatocytes. It's also the case that HDL helps clear these toxins in the liver

So putting two and two together, what do you think about stopping cholesterol lowering drugs in those already on them when having an infection?

But not everything is that simple. Here's some clinical evidence based on real whole person, human responses. Statin use associates with reduced likelihood of pneumonia - substudy from the Jupiter trial.

@drjminpat's work with @teamneutrophil also showed in a pilot randomised controlled trial that statins could reduce the risk of pneumonia becoming sepsis

And this was replicated in another trial by the same group led by @e_sapey where it was shown that giving these drugs improved clinical outcomes in pneumonia while improving the efficiency of neutrophil movement and reducing potentially lung damaging neutrophil behaviours

In patients with severe degrees of illness, like sepsis, it's been more difficult to show an effect of these drugs on disease outcome. But importantly there is no signal to harm and a suggestion of benefit for those already on these medicines. But what about severe lung failure??

Again, difficult to show effect in severe lung failure (ARDS) which is what COVID-19 patients have in ICU. In this trial of Simvastatin by HARP-2 investigators including @dfmcauley @perkins_gd and @armycritcare no benefit was shown of statins, though no harm either, HOWEVER...

Researchers identify two groups of patients across ARDS trials. A high mortality inflamed one, and one with lower mortality, less inflamed. We usually see 1:4 red: blue in ARDS due to pneumonia, but may be seeing much more red in COVID. Red has high neutrophil markers (IL-8)

The importance of this is when we re-analyse HARP-2 by looking at these groups, statins have mortality benefit in the inflamed red group only. Because of the way it was done, this needs confirmation in another trial so this only suggests the drugs might work in specific ARDS pts

It's also worth considering that acute cardiovascular events increase significantly after viral and bacterial pneumonia, and that stopping a prognostically beneficial CVS drug in the middle of a pneumonia is possibly unwise to say the least

So now what can we conclude about statins in covid-19? Should patients routinely stop them as hinted at by @DrAseemMalhotra ?

So how can we explain the discrepancy between low LDL & bad infection outcomes, and a possible benefit of cholesterol lowering therapies in infection? It's complex, but first thing is that before Abx, evolution strategised withstanding infection just enough to reproduce. Ugly.

Then, when obesity & atheroprone diets were less uncommon, a naturally higher LDL was probably protective against infection & maximised chances of reaching reproductive age, though the strategy was clearly not watertight. People still died early from infection

Now we're living longer, and getting bigger. It also happens that central obesity seems to make infection outcomes worse, but even obesity and LDL dynamics interact to determine infection outcomes. Complex, not simple.

LDL is produced, transported and cleared. Cellular cholesterol metabolism also determines immune function. So a low blood LDL level in individuals hides a lot & isn't the same as a population signal: blood levels make simple headlines for people with simple messages. Beware!

In summary, although natural variation in LDL associates with poor infection outcomes, drug therapies that reduce cholesterol do not make you become a poor outcome patient, and may even protect. Don't stop your statin without your doctor's advice, and don't dose either! END