The Food and Drug Administration (FDA) has issued a statement regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with coronavirus disease 2019 (COVID-19).
Commentary by Diane Hanna, DNP, DcNP:
In the early days of the pandemic there was a widely circulating myth that using NSAIDs or homeopathic anti-inflammatories in healthy individuals could increase one’s risk for contracting SAR-CoV-2 virus and having a poor outcome. This information continues to be widely shared across the internet, social media, and online media outlets with little evidence. Where did this notion originate from?
In the early days of the pandemic, medical teams across the globe tried to get their arms around treatment protocols and options for acutely ill patients stricken with COVID-19. In the absence of any evidence-based protocols for treatment for this novel virus, the initial diagnostic criteria and treatment approaches were similar to the management of influenza patients.
Anecdotal reports from several countries suggested that during early intervention and treatment of newly diagnosed and presumptively acutely ill COVID-19 patients, NSAIDs and systemic steroids may have contributed to worsening of disease and potentially linked to poorer patient outcomes.
The rapid progression of ARDS in a subset of COVID-19 positive patient population lead to the hypothesis that the mechanism of action of anti-inflammatories may have negative immunological complications. The first theory was that NSAIDS may act as a positive feedback loop that could increase the severity and intensity of cytokine storm, which often leads to multiorgan failure. The second hypothesis was that anti-inflammatories may dampen down the immune systems ability to respond to infection and could potentially contribute to the risk of secondary infections seen in influenza patients. While co-infections are now starting to be reported in COVID-19 patients, secondary pulmonary infections are not widely reported.
There was international discussion in reference to Ibuprofen use in patients with COVID 19. It is important to note that it is common practice in France not to use Ibuprofen for the treatment for any upper respiratory infections. In 2019, “on the advice of the National Agency for the Safety of Medicines and Health Products, French health workers have been told not to treat fever or infections with ibuprofen. Experts in the UK backed this sentiment. Paul Little, a professor of primary care research at the University of Southampton, said that there was good evidence “that prolonged illness or the complications of respiratory infections may be more common when NSAIDs are used—both respiratory or septic complications and cardiovascular complications.” (British Journal of Medicine, 2019)
The early clinical observations and the discussion of the 2019 BMJ data snowballed into a widely perpetuated myth that healthy individuals should stop using NSAIDS as it put them at risk for contracting the disease or worsening their prognosis.
There is contradictory data contained in a 2006 publication (C Amici et al.) suggesting that indomethacin has antiviral activity and could be utilized as a potential treatment for SARS-CoV-1 and this data could be useful or extrapolated to SARS-CoV-2. To further examine the potential benefits of NSAIDs, a phase 3 trial of naproxen versus the standard of care in patients has begun enrollment on March 27, 2020. The study will examine “patients with symptoms of respiratory distress caused by COVID-19 may be reduced by drugs combining anti-inflammatory and antiviral effects. This dual effect may simultaneously protect severely ill patients and reduce the viral load, therefore limiting virus dissemination. We want to demonstrate the superiority of naproxen (drug) treatment addition to standard of care compared to standard of care in term of 30-day mortality.”
Currently there is no clinical trial data that concludes that it is detrimental to use NSAIDs in healthy individuals. Anecdotal clinical reports have suggested that COVID-19 patients’ poorer outcomes may have been related to anti inflammatories. There are no clinical studies to support that hypothesis. As expected, treatment approaches may vary by country, institution and individual medical teams. Currently treatment decisions across the spectrum in COVID-19 patients is supported by clinical judgement and limited data.