Statins and In-Hospital Mortality in Diabetics With COVID-19

Statins Reduce Mortality in Patients With Diabetes and COVID-19

The strange thing about COVID-19 is its variability—one person has no symptoms while another ends up on a ventilator and dies. This variability of outcomes is coming from the exact same virus. This means that difference is in the patients, not the virus. Maybe it’s their genetic makeup or the diseases they have or the medications they are taking? The fastest way to figure this out is to investigate patients in large databases to look for some patterns.

In this case, the investigators focused on the use of statin therapy to see if that could explain some of the variability. It is well-known that this virus causes inflammation and even cytokine storms, and it is also known that statins can lower inflammation, and, hence, statin therapy is a logical target for investigation. 

This study was done in a single center in the Bronx, New York, where they evaluated 4252 patients who were admitted with COVID-19 to see if there was a protective effect of statins or not. The investigators also divided the patients into categories of those having diabetes and those who did not have diabetes.

In patients with no diabetes, the mortality rate was the same whether they were on statins or not (20% vs 21%; P = .82). However, among patients with diabetes, there was a significant difference. On multivariate analysis, which adjusted for age, sex, history of atherosclerotic heart disease, Charlson comorbidity index, presenting diastolic blood pressure, respiratory rate, pulse oximetry measurement, serum glucose, serum lactic acid, serum creatinine, and intravenous antibiotic use during hospitalization, there was a 49% reduction in death (HR, 0.51; 95% CI, 0.43–0.61; P < .001) in favor of statin therapy. Even with full propensity score matching, there was still a significant 12% reduction of in-hospital death (HR, 0.88; 95% CI, 0.83–0.94; P < .01) in favor of statin therapy. These results would seem to say that, in patients with diabetes and COVID-19, statins can reduce death.

Now the explanation is not yet clear. The authors suggested that it might be the anti-inflammatory effect of statins that is the driving force. C-reactive protein (CRP) was slightly less in the statin group (CRP [IQR], 10.2 [4.5–18.4] vs 12.9 [5.9–21.4] mg/dL; P < .01), but this small difference would not be able to explain the rather significant death reductions, and it did not seem to work in patients without diabetes.

Another possible explanation has to do with accumulated cellular damage. We all know that patients with comorbidities like diabetes, hypertension, and CVD, along with old age, have higher mortality risk if they contract COVID-19. So, one theory is that all of these diseases cause damage to the cell. Once there is enough damage in the cell, then the cell has an auto-destruct sequence, which basically allows it to kill itself. This is a great way to get rid of damaged or bad cells from the body. 

Now imagine I am 80 years old, with diabetes and hypertension. My cells would have accumulated some damage, maybe not enough to trigger the auto-destruct sequence yet, but definitely some damage. Along comes the virus, and it increases the damage in the cell, and this pushes the damage level into the self-destruct range. Now the cell auto destructs. The virus is causing this destruction in all the lung cells that have been infected, so that means mass destruction, which then leads to organ failure or a cytokine storm, which then leads to death. 

Now imagine having a statin on board. It reduces the level of damage in the cell. So, patients on statins have fewer damaged cells, and, hence, have some buffer.

Why do we need diabetes to be in the mix? Without diabetes, the cells may not be damaged enough. A cell that already has a good deal of buffer is unlikely to get pushed to auto destruct. A statin provides a greater buffer, but it’s not needed in someone without diabetes, and there is no associated reduction in death rates. However, diabetes would cause the cells to have lots of accumulated damage and that’s when the statin will truly shine. It reduces the cellular damage and thereby creates some buffer so that the cells will not be pushed over the threshold by the virus, and hence, a death may be averted.

Of course, all of this is speculation, and the exact answer is not yet known. But, for the time being, please keep all your patients on statin therapy. And for the higher risk patients (ie, those with multiple comorbidities), please put them on statins if they are supposed to be on a statin. Maybe the statin will help protect them from the auto-destruct sequence. Even if it does not, you have still protected them against a heart attack or stroke.