Rationales and uncertainties for aspirin use in COVID-19: a narrative review

Abstract

Objectives: To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19.

Design: Narrative review.

Setting: The online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance.

Participants: Not applicable.

Results: A review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable.

Conclusion: The authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40-70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin's protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.

Keywords: COVID-19; cardiovascular diseases; global health; infectious disease medicine; respiratory system.

Figure 1

COVID-19-induced inflammation, endotheliopathy and thrombosis. Alveolar-capillary endothelial cells can be activated by SARS-CoV-2 infection leading to cytokine release and expression of vascular adhesion molecules. Also, endothelial cells express ACE which allows infection by SARS-CoV-2. This could trigger endothelial dysfunction and pyroptosis that also increase the pro-inflammatory stimuli and thrombogenic events. This figure was used with permission from the publisher Wolters Kluwer Health (license number: 4938390247706). ‘The Creative Commons license does not apply to this content. Use of the material in any format is prohibited without written permission from the publisher, Wolters Kluwer Health. Please contact permissions@lww.com for further information’. ICAM-1, intercellular adhesion molecule 1; IL, interleukin; TNF, tumour necrosis factor.

Figure 2

Mechanisms in which aspirin can manipulate the process in sepsis and acute respiratory distress syndrome: aspirin inhibits the enzyme COX, preventing the formation of pro-inflammatory thromboxane and prostaglandins. It also inhibits the release of NFκB from its inhibitor IkB, preventing the formation of pro-inflammatory cytokines and chemokines. Aspirin leads to the production of aspirin-triggered lipoxin, which induces the release of NO, inhibits the production of IL-8 and MPO, restores neutrophil apoptosis and promotes resolution. Aspirin increases the production of NO, resulting in reduced migration and infiltration of neutrophils and reduced permeability of the endothelium. 15-epi-ATL, aspirin-triggered 15-epi-lipoxinA4; AA, arachidonic acid; COX, cyclooxygenase; eNO, endothelial nitric oxide; IKK, IkB kinase; IL-8, interleukin 8; MPO, myeloperoxidase; NFκB, nuclear factor kappa B; NO, nitric oxide; PGE 2, prostaglandin E2; TXA 2, thromboxane. This image is licensed under the Creative Commons Attribution 4.0 International License found at http://creativecommons.org/licenses/by/4.0/.