EM:RAP 2020 March 19th Breaking News - COVID-19 and NSAIDs
Sean Nordt MD, PharmD
On March 11, 2020 the Lancet published “Are Patients with Hypertension and Diabetes Mellitus at Increased Risk for COVID-19 Infection?” and this led to the Minister of Health of France Olivier Veran, M.D. sending a tweet raising potential concerns of anti-inflammatory medicines e.g., ibuprofen in patients with COVID-19. This was followed by reports in the popular press.
So, what is this all about?
COVID-19 (SARS-CoV2) can cause severe acute respiratory syndrome. This virus has spike proteins that use ACE2 as a receptor for host cell entry. ACE2 is a metallocarboxypeptidase with some homology to ACE. ACE2 is also expressed in large amounts in lungs particularly Type II pneumocytes, enterocytes in the intestines and found in the kidneys and blood vessels.
In the Lancet article the authors raised concerns patients with co-morbid conditions including diabetes mellitus and hypertension were found to have more severe disease and increased mortality. This is suggested to be from increased expression of ACE2 allowing for increased viral receptor binding. Diabetes mellitus itself can increase ACE2 but certain medications can increase ACE2 including ACE inhibitors, ARBs and thiazolidinediones e.g., rosiglitazone, pioglitazone. In addition, NSAIDs e.g., ibuprofen can increase ACE2 expression.
This raises the concern of using NSAIDs in the symptomatic treatment of patients with COVID-19 potentially worsening disease.
This is theoretical but does cause reason to consider.
Whether short courses of NSAIDs increase expression is unknown but and has raised differing opinions. Some health authorities and experts have recommended avoiding NSAIDs including the WHO. Others have dismissed as unlikely. Furthermore, infectious diseases specialists have raised the question whether there should limited treatment of fever as may affect the natural ability to fight infection.
Though data is lacking at this point in time it may be prudent to use acetaminophen (paracetamol) as first line agent unless contraindicated. Using NSAIDs e.g., ibuprofen judiciously and in the lowest dose possible and infrequently is probably safe and should be considered on a case per case basis. Another alternative would be to alternate acetaminophen (paracetamol) with NSAIDs rather than use NSAIDs exclusively.
Whether ACE inhibitors or ARBs should be discontinued is also debatable. The authors of the Lancet article suggest alternatives e.g., calcium channel blockers whereas some societies (see The Coronavirus Conundrum: ACE2 and Hypertension Edition) argue against this. From the emergency medicine perspective this decision should be made by or in consultation with the patient’s prescriber or the admitting team.
Fang L, Karakalpak’s G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection. Lancet Published: March 11, 2020DOI:https://doi.org/10.1016/S2213-2600(20)30116-8
Jia HP, Look DC, Shi L, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 2005;79:14614-14621
Wu Y. Compensation of ACE2 function for possible clinical management of 2019-nCoV-induced acute lung injury. Virologica Sinicia
Day M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ 2020;368m1068
The Coronavirus Conundrum: ACE2 and Hypertension Edition. http://www.nephjc.com/news/covidace2. March 14, 2020
Ian L. - March 19, 2020 6:00 PM
ACE inhibitors cause cough and some have seen in acute bronchitis that patients on ACE's have prolonged coughing for weeks -If a patient is in the catarrhal phase that is the 5 day cough fever sore throat before the pneumonia you could argue patients Ought be taken off ACE's if it is for blood pressure and another tablet eg CCB or Thiazide is available --also in diabetics on ACE for benefit years away . -With heart failure Sudden withdrawal if more problematic .
Sean N. - March 19, 2020 6:19 PM
Hi Ian, thank you for the comment
If you as the emergency clinician are concerned ACE inhibitor causing cough and aggravating the cough or prolonging course would recommend discussing with the patient to discuss with their primary care provider, cardiologist, etc. and mention there are other alternatives for blood pressure they can use eg, CCB
At this time though for the COVID-19 patients the recommendation is to continue ACE inhibitors and ARBs ie, do not discontinue just because have COVID-19
Sean N. - March 19, 2020 6:29 PM
As Mel mentions in the end of the audio segment the WHO has now changed it's position on NSAIDs and COVID-19 in tweet
"Based on currently available information, WHO does not recommend against the use of ibuprofen" from March 18, 2020 which is change from previous when WHO recommended that people suffering COVID-19 avoid taking ibuprofen.
Will let you know if any additional data comes on subject