Anti-inflammatory drugs and the renin-angiotensin-aldosterone system: Current knowledge and potential effects on early SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 19 (COVID-19), and is genetically related to the 2003 SARS and Middle East respiratory syndrome (MERS-CoV) coronaviruses. Recent studies have reported that similar to SARS-CoV, this strain expresses a spike protein (S) with a receptor binding domain (RBD) that binds to angiotensin-converting enzyme 2 (ACE2) – an enzyme expressed mostly in the endothelium, kidneys, heart, gastrointestinal tract and lungs – to facilitate viral entry and intracellular replication. Incidentally, the renin-angiotensin-aldosterone system (RAAS) is integral to physiologic control of both ACE and ACE2 expression, and is an essential system utilized by SARS-CoV-2, albeit with varying schools of thought on how it can affect viral entry. In this paper, we will review current knowledge on the RAAS and how it can be affected by non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid use at the organ and cellular levels. We will then discuss the relevance of these interactions on organ-specific ACE2 expression, and provide scientific insights on how this mechanism can potentially affect SARS-CoV-2 infection in the early phases of disease. From the standpoint of other known viruses, we will then aim to discuss the potential uses or restrictions of these drugs in viral infection, and provide an update on relevant studies about COVID-19.