Nature: Protective Effects of Statins on COVID-19 Risk, Severity and Fatal Outcome

 

#16,883

Between our rapidly dwindling armamentarium against COVID infection (see FDA Limits Use Of Sotrovimab Monoclonal Antibody As Rising BA.2 Erodes Effectiveness), and declining protection against infection by vaccines, there is renewed interest in finding existing treatments that aren't invalidated every time the virus shifts antigenically. 

Earlier this year we also saw the FDA withdraw their EUAs on bamlanivimab and etesevimab (administered together) and REGEN-COV (casirivimab and imdevimab) (see FDA Removes Authorization For Two Monoclonal Antibody Therapies Due To Omicron).

 

Early hopes that convalescent plasma - harvested from those who had recovered from the illness - would be a game changer were quelled after study after study (see BMJ: Clinical Trial On Convalescent Plasma Showed Little Benefit For COVID-19) failed to show much effect.

In the fall of 2020,  Eli Lilly & ViralClear Halted Their Clinical Trials For COVID-19 Treatments after early data suggested that the drugs being tested were not providing a benefit to hospitalized COVID patients.

There are two oral antivirals (Paxlovid and molnupiravir) still available, but there are no guarantees how long both will remain effective against future variants. 

For many years Dr. David Fedson – former Professor of Medicine at the University of Virginia School of Medicine and formerly Director of Medical Affairs, Aventis Pasteur MSD - has championed the idea that we should be looking at cheap, easy to produce, generic statins for this role, which he believes may help modulate the immune response.

Over the years we've looked at his proposals, and some (admittedly) conflicting studies, on the effectiveness of statins against influenza and pneumonia.

Pandemic Influenza: A Potential Role for Statins in Treatment and Prophylaxis - David S. Fedson

New Approaches to Confronting an Imminent Influenza Pandemic - Dr. Fedson and Peter Dunnill, DSc,FREng

Statins & Pneumonia: Revisited

Study: Statins, Influenza, & Mortality

We've also seen a number of reports and/or studies suggesting that statins might be useful in reducing the impact of COVID-19.

Statins Reduce COVID-19 Severity, Likely by Removing Cholesterol That Virus Uses to Infect

Meta-analysis of Effect of Statins in Patients with COVID-19

Protective role of statins in COVID 19 patients: importance of pharmacokinetic characteristics rather than intensity of action

But the first big study (Dec. 2020) we looked at (see BMJ Open: Association Between Statin Use And Outcomes in Patients with COVID-19) was far from encouraging, failing to find a survival benefit among patients who were taking statins when infected.

Another (relatively small) study from Johns Hopkins (Sept 2021) (see Statins Likely Not Helpful in Reducing Covid-19 Mortality or Severity) warned that statins may even be associated with an significantly increased risk (18%) of more serious illness. 

Yesterday, however, the Journal Nature published a large population-based study out of Sweden which may help revive interest in statins as a potential therapeutics/preventatives for COVID.

This is a long and detailed report, and while (spoilers ahead) it falls far short of proving its case, it does suggest that statin users had a 14% lower risk of death from COVID. 

And it isn't the only recent study to do so.  

Last month, a study appearing in JAHA - this time out of France - found that statin use was associated with a 16% lower risk of hospitalization for COVID‐19, and a similar reduction of in‐hospital deaths from COVID‐19.

Conflicting studies are nothing new, and all studies suffer from various (and often different) limitations. While neither of these new studies prove statins are beneficial for the treatment and/or prevention of COVID, they do suggest that more research is warranted. 

Research that may well be needed more for the next pandemic, than for this one. 

 

Protective effects of statins on COVID-19 risk, severity and fatal outcome: a nationwide Swedish cohort study

Ailiana Santosa, Stefan Franzén, Jonatan Nåtman, Björn Wettermark, Ingela Parmryd & Fredrik Nyberg

Scientific Reports volume 12, Article number: 12047 (2022) Cite this article

Abstract

The impact of statins on COVID-19 remains unclear. This study aims to investigate whether statin exposure assessed both in the population and in well-defined cohorts of COVID-19 patients may affect the risk and severity of COVID-19 using nationwide Swedish population-based register data. 

A population ≥ 40 years was selected by age/sex-stratified random sampling from the Swedish population on 1 Jan 2020. COVID-19 outcomes were identified from the SmiNet database, the National Patient Register and/or Cause-of-Death Register and linked with the National Prescribed Drug Register and sociodemographic registers. Statin exposure was defined as any statin prescriptions in the year before index date. 

In Cox regressions, confounding was addressed using propensity score ATT (Average Treatment effect in the Treated) weighting. Of 572,695 individuals in the overall cohort, 22.3% had prior statin treatment. 

After ATT weighting, protective effects were observed among statin user for hospitalization and COVID-19 death in the overall cohort and onset cohort. In the hospitalized cohort, statin use was only associated with lower risk for death (HR = 0.86, 95% CI 0.79–0.95), but not ICU admission.  

Statin-treated individuals appear to have lower COVID-19 mortality than nonusers, whether assessed in the general population, from COVID-19 onset or from hospitalization.

(SNIP)

Discussion

This study investigated the impact of prior statin treatment on a range of five different COVID-19 outcomes in three different Swedish population-based cohorts—general population, individuals with COVID-19 onset and a COVID-19 hospitalization cohort. Our main findings show that prior statin treatment was significantly associated with a reduced risk of COVID-19 test-positivity, diagnosis, hospitalization and mortality in the 3 studied population cohort. 

These findings strengthen and support evidence on the hypothesis of pleiotropic protective effects of statins in COVID-19 from prior cohort studies23,24,25,26,27,28,29,30 and align with evidence summarized by recent meta-analyses and systematic reviews on the association of statin use and the potential protective effects against progression and severity of COVID-1915,16,18,31,32. A recent Swedish cohort study using register data with a smaller sample size limited to the Stockholm Region similarly showed statin use to be a protective factor for COVID-19 death29. That study had shorter follow-up than ours, but similar to our main exposure definition, defined statin exposure broadly as any statin treatment initiated before the pandemic, not regular statin use).

(SNIP)

Conclusions

Findings from this study provide broad evidence of a beneficial effect of prior statin exposure on COVID-19 mortality in all the three cohort populations studied (overall population, COVID-19 onset and COVID-19 hospitalization cohorts), as well as less strong effects on other COVID-19 outcomes along the COVID-19 progression spectrum of outcomes that we studied. Together with prior available scientific evidence, both mechanistic and epidemiological, our findings support potential investigation into repurposing of statins for COVID-19 protection.

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