The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, driven by the emergence of new and more transmissible variants. The mortality and long-term morbidity are known to be probably fueled by the cytokine storm that is typically observed in patients with severe and critical COVID-19.
Much attention has been focused on ways to reduce the deadly exaggeration of normal inflammatory reactions to this pathogen. A new research paper posted to the medRxiv* preprint server describes the alleviation of hyper-inflammatory phenomena following the administration of statins, drugs more widely known for their use in reducing blood cholesterol levels, to patients with COVID-19
Study: The protective association between statins use and adverse outcomes among COVID-19 patients: a systematic review and meta-analysis. Image Credit: Nucia / Shutterstock
With severe COVID-19 pneumonia, pro-inflammatory cytokines such as tumor necrosis factor (TNF), IL-6 and IL-1β are produced in abundance in response to the viral infection. As the disease progresses, the systemic effects of these cytokines leads to increased vascular permeability, multi-organ failure and death.
Lipid metabolism is strongly suspected of playing a pivotal role in this inflammation since cytokines are lipid derivatives, and lipids are essential elements of the cell membranes that help internalize the virus and facilitate further replication and transcription.
High cholesterol levels in the tissues have been shown to promote SARS-CoV-2 endocytosis into the host cell, allowing infection establishment. Statins act by inhibiting the enzyme 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inside the cells. This action not only prevents upregulation of the myeloid differentiation primary response 88 to the presence of the virus but leads to increased expression of the protective angiotensin-converting enzyme 2 (ACE2) molecule on the cell membranes.
Earlier studies
Prior research suggested reduced mortality as the result of statin use, but some studies reported contradictory findings. A comprehensive overview of the current literature is lacking. The available meta-analyses of statin use in COVID-19 patients do not report whether the patients were put on statins following hospitalization or if these drugs were in prior use.
The current preprint is a meta-analysis of the studies carried out so far on this aspect of COVID-19 management.