There is mounting, though not conclusive, evidence that aspirin may be offered to these patients as long as they do not have any contraindication such as a bleeding tendency or previous bleeding in the brain.
California, US: During the ongoing Covid-19 pandemic the vast majority of patients with SARS-CoV-2 infection have a mild to moderate illness that does not merit hospitalization. There is an urgent, unmet medical need to slow the disease in its early stages and prevent it from spiralling out of control, thereby minimizing the need for hospital admission, oxygen support and remdesivir, all in short supply. However, an effective treatment for outpatients with mild to moderate Covid-19 disease has remained elusive till now. Corticosteroids and the anti-viral drug remdesivir have been demonstrated to improve outcomes in hospitalized patients with severe disease, but not in outpatients with milder disease. Unfortunately, despite lack of scientific evidence, corticosteroids such as prednisone, prednisolone or dexamethasone, and antibiotics such as azithromycin or doxycycline are being widely used in the outpatient setting. This practice is leading to catastrophic emergence of mucormycosis, commonly referred to as black fungus, in patients who have recovered from Covid. Growth of black fungus is fuelled by corticosteroids adding insult to an immune system that has been injured by the virus itself, while antibiotics destabilize the microbial flora in the nose and mouth by killing the bacteria that keep fungal growth in check. A potentially effective treatment has emerged over the past few months that may offer hope for outpatients with Covid, thereby mitigating reliance on steroid and antibiotics.
Aspirin, an age-old drug, offers that ray of hope to millions of newly infected patients with early and mild disease. There is mounting, though not conclusive, evidence that aspirin may be offered to these patients as long as they do not have any contraindication such as a bleeding tendency or previous bleeding in the brain. Aspirin is currently being tested in randomized placebo-controlled clinical trials in outpatients with Covid-19. These trials include the ACTIV-4 trial sponsored by the National Institutes of Health, USA, and the ACTCovid19 trial sponsored by the Population Health Research Institute, Canada. The escalating second surge and increasing mortality rates in Southeast Asia and South America exhort us to act now based on available evidence, and not wait for completion of the ongoing trials.
Early use of aspirin is supported by the growing understanding of the critical role that clotting plays in this disease. Even in the early and mild disease it has been demonstrated that tiny blood clots form in the small blood vessels in the lungs, referred to as lung capillaries. This process is called microvascular thrombosis. These clots impede the transfer of oxygen from the air sacs to the blood. As the clots become more extensive and widespread, the oxygen level in the blood drops and hypoxia ensues. Aspirin can potentially slow the progression of Covid-19 by inhibiting clot formation and inflammation, while promoting resolution and healing. At least four recent studies, both prospective and retrospective, suggest that a tablet of low-dose aspirin, 75 mg to 100 mg, taken daily can decrease the need for hospitalization, oxygen support, and artificial respiration. In a recent retrospective study*, 6,300 Covid-19 positive American Veterans with preexisting aspirin prescription were compared with 6,300 Covid-19 positive patients matched via propensity scores but not taking aspirin. Aspirin use was associated with a statistically and clinically significant decrease in overall mortality of over 50% at 15 days and 30 days, cutting the odds of mortality by more than half.
Aspirin is a readily available, over the counter medicine. It is very safe when taken by adults without a bleeding tendency or risk of hemorrhage. The economic burden of hospitalization for a common Indian with a monthly per capita income is prohibitive. Aspirin costs $1-2 for a 30-day course as an outpatient, while remdesivir administered during hospitalization costs $350 for a 5-day course. An international panel of experts needs to be convened urgently to conduct a risk-benefit analysis of aspirin in early Covid-19 based on available evidence, and to determine if an interim analysis of ongoing clinical trials is needed to provide guidance for or against use of aspirin. Rapid deployment of aspirin can potentially reduce the burden of disease for the patients and the health care system in many developing countries battling this second surge of Covid-19.
Dr Ajay Gupta, MBBS, MD, is Clinical Professor, Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine; President & CSO, KARE Biosciences (www.karebio.com)
* Osborne TF, Veigulis ZP, Arreola DM, Mahajan SM, Röösli E, Curtin CM. Association of mortality and aspirin prescription for Covid-19 patients at the Veterans Health Administration. PLoS One. 2021;16(2):e0246825. Published 2021 Feb 11. doi:10.1371/journal.pone.0246825