Medication Use and COVID-19

As the world scrambles to contain COVID-19, a lot of information – and misinformation – is spread throughout the news and social media sites. There has been much published regarding the ways in which we can combat COVID-19, from drugs we can use for treatment (new or old), drugs we should not use, and vaccines that are being developed. There have also been assertions regarding over-the-counter remedies. Our goal is to relay evidence-based data we have available at the time of this publication and clear up some of the confusion. This is a fluid situation; the data is constantly being refined and recommendations can change on a daily, if not hourly, basis.

For now, supportive care is the mainstay of treatment. This includes oxygen support and if needed, intubation and mechanical ventilation. Additional investigational approaches are being evaluated but evidence, at this point, is lacking to determine their effectiveness. We do know that some medications, such as those used to treat influenza (e.g. Tamiflu®) are NOT effective. Investigators are looking at other antiviral medications such as remdesivir, sarilumab, tocilizumab, etc. to assess their effectiveness to treat COVID-19 but there are no solid answers yet. So far, the HIV medication, lopinavir/ritonavir, does not look promising for severe COVID-19 but studies have been started to look at its use earlier in the course of treatment.

The Food and Drug Administration has recently issued an emergency use authorization for remedesivir for hospitalized children and adults with severe COVID-19 infection. There are multiple clinical trials underway for this antiviral agent, but if preliminary results are confirmed, there appears to be some benefit to remdesivir use for faster recovery times.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, etc., has been questioned after the French Health Minister tweeted they may increase the risk of COVID-19. This seems to be an extension of a 2019 warning in France that NSAIDs may make infections worse based on data mostly involving strep infections. The thought is that ibuprofen may increase the number of ACE2 receptors on cells. ACE2 is the receptor that the SARS-CoV-2 virus, uses to enter the cell. But there is currently no evidence that NSAIDs worsen COVID-19. We do know that NSAIDs can cause bleeding ulcers in the stomach and intestines, increases the risk of bleeding overall, as well as exacerbating heart failure and hypertension, especially in older patients. Therefore, the first-line choice for fever and aches should be acetaminophen (Tylenol®).

You may also be hearing that blood pressure medications in the ace-inhibitor (e.g. lisinopril) or angiotensin receptor blocker (e.g. losartan) classes may increase the risk of getting serious complications with COVID-19. This is from speculative reports based on the fact discussed above that the coronavirus uses ACE2 to enter the cell. This risk is only hypothetical at this point and there is currently NO evidence to suggest these medications may increase the risk of getting or having a more severe case of COVID-19. In fact, researchers are currently studying the use of losartan to make COVID-19 LESS severe but there is no evidence this is the case yet either.

A couple of ‘older’ drugs – chloroquine and hydroxychloroquine – have been getting lots of press lately. They are thought to prevent the virus from multiplying, and they help to modulate the immune system. But the initial evidence was ONLY lab-based studies that showed reduced viral load (the quantity of virus in a given volume) in animal models that are sometimes very difficult to translate to human effectiveness. The buzz really took off when there was a French report of six patients who cleared the virus after 6 days on hydroxychloroquine and azithromycin – but this is a very small sample size. The plus side is most of these French patients did show favorable outcomes in this observational study. In contrast, two small randomized trials from China found mixed results with hydroxychloroquine. Investigators have pointed out that these reports have many flaws in them and it’s too soon to say that reducing viral load correlates to better COVID-19 outcomes. In addition, these medications are not free of side effects. Hydroxychloroquine can cause cardiac issues resulting in cardiac failure and death, psychiatric effects, eye problems, and other serious side effects. Azithromycin can also alter the conduction of the heart, so combining this with hydroxychloroquine poses the risk of added serious complications. There is really

no good evidence at this point that these medications should be used in the community to treat or prevent COVID-19 and they should be reserved for hospitalized patients or clinical trials.

Efforts are currently underway to prepare a vaccine against the SARS-CoV-2 virus that causes COVID-19. The first vaccine to be tested is using a new technique to utilize our own cells to create a viral protein that will allow our body to create a robust immune response prior to potential exposure to the invading virus. There are multiple pharmaceutical manufacturers exploring and preparing their own vaccine testing. As of the writing of this blog, there were 115 vaccine candidates, with 78 active, and 5 currently in phase 1 on human volunteers. There is optimism that a vaccine may be available in limited use in early 2021.

Immune boosters such as Airborne and Emergen-C are in big demand right now. But know that there is no good evidence that these or other supplements such as garlic, zinc, or echinacea can prevent COVID-19 or other viruses. But there should be little risk of harm if anyone would want to try these for themselves. Note that elderberry has been shown to reduce the symptoms of influenza but of course, there is no data yet with COVID-19.

In summary, if you have questions, your best resource is to ask your healthcare professionals and be leery of advice from sources other than the Centers for Disease Control (CDC) and the World Health Organization (WHO). In the meantime, we should continue to practice those things that we know are helping prevent the spread of COVID-19: social distancing, excellent hand hygiene through the use of washing and hand sanitizers, and staying at home as much as possible.

References

1. Lancet Respir Med Published online Mar 11, 2020; doi:10.1016/S2213-2600(20)30116-8
2. JAMA Published online March 24, 2020; doi:10.1001/jama.2020.4812
3. N Engl J Med Published online March 30, 2020; doi:10.1056/NEJMsr2005760
4. https://www.nature.com/articles/d41573-020-00073-5
5. https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician
6. www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19
7. Int J Antimicrob Agents Published online Mar 20, 2020; doi:10.1016/j.ijantimicag.2020.105949
8. www.groupedeveillecovid.fr/blog/2020/03/28/clinical-and-microbiological-effect-of-a-combination-of-hydroxychloroquine-and-azithromycin-in-80-covid-19-patients-with-at-least-a-six-day-follow-up-an-observational-study/
9. J Zhejiang Univ Published online Mar 6, 2020; doi:10.3785/j.issn. 1008-9292.2020.03.03
10. https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2.full.pdf
11. www.ama-assn.org/delivering-care/public-health/joint-statement-ordering-prescribing-or-dispensing-covid-19
12. www.ashp.org/Pharmacy-Practice/Resource-Centers/Coronavirus
13. Pharmacist’s Letter Online, Accessed April 6, 2020
14. Up-to-Date, Accessed April 6, 2020,
15. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins