Sunday morning March 15th and total worldwide confirmed #COVID-19 cases stand at 156,400 of which 2,952 are in the US. Of these, we have had 57 deaths (1.9% mortality rate) and 12 confirmed recoveries. Please note that the mortality rate is unlikely to be accurate for several reasons including the lack of accurate case acertainment (due to lack of test kits primarily) as well as where we are in the epidemic. A true case fatality rate (CFR) cannot be calculated until towards end of an epidemic. However, given that the CFR in China has been estimated at 2.3% and thus far in South Korea it stands at 0.5% looking at a moving average of our CFR may provide some insights.
In this post I would like to highlight data we have thus far on the role of medications in interrupting either infectivity (acquisition) of the virus, or in modifying its severity (i.e. making it more or less lethal). Olivier Veran, the Secretary of Social Affairs and Health in France, tweeted this morning the following;
Taking anti-inflammatory drugs (ibuprofen, cortisone, …) could be a factor in worsening the infection. If you have a fever, take paracetamol [Tylenol/acetaminophen]. If you are already on anti-inflammatory drugs or in doubt, ask your doctor for advice.
France is now advising all people to stop taking NSAIDs like Motrin, Aleve, Ibuprofen altogether to avoid side-effects in case of a potential COVID-19 infection. Instead of Ibuprofen, they are suggesting Tylenol. Why? Their supposition is that NSAIDs prevent the inflammatory responses of the body, a natural reaction that happens to fight the coronavirus after infection. By preventing inflammation, these drugs could mask the severity of a disease, and reduce the capacity of the immune system to deal with the pathogen.
A similar discussion has emerged regarding the role of two classes of medications commonly used to treat hypertension:
ACE inhibitors (identifiable by their suffix -pril) and ARBs (suffix -sartan). The angiotensin converting enzyme (ACE) controls blood pressure by regulating the volume of fluids in the body. Some research has shown that the ACE2 protein was the main receptor for the SARS virus and therefore advocacy for stopping these effect medications has begun. However, European Society for Cardiology did not agree and noted that in stable patients with COVID-19 infections or at risk for COVID-19 infections, treatment with ACEIs and ARBs should be continued.
Best summed up by Dr. Mohammad Majiid (UTHealth; Houston who has studied the links between influenza and cardiovascular disease: “There is a lot of misinformation out there,” he said. “The ACE inhibitors and ARBs do not act on this receptor directly so they are not going to affect the activity of the virus for these cells. The proposed interactions of ACE inhibitors and ARBs with the virus is purely hypothetical with no reliable data to justify any deviation from current practice guidelines.”
Three medications in particular have generated interest (and questions from my patients!) as all three are currently in early phase COVID-19 treatment trials in China. These are: Kaletra / Aluvia (a combination lopinavir and ritonavir), the generic drug chloroquine phosphate and the generic drug hydroxychloroquine.
Kaletra is an ntiretroviral agents for human immunodeficiency virus (HIV). It is under investigation in 16 ongoing or planned clinical trials for Covid-19 in China.
Chloroquine is a generic anti-malarial medication that is believed to have broad-spectrum antiviral activities. Note that it it is not approved as an antiviral agent but there remains a strong rationality for the use of chloroquine to treat infections with intracellular micro-organisms. It has been used to treat Coxiella burnetii, the agent of Q fever as well as Tropheryma whipplei, the agent of Whipple’s disease. Data from China has shown that chloroquine could reduce the length of hospital stay and improve the evolution of COVID-19 pneumonia leading to recommendation for administration of 500 mg of chloroquine twice a day in patients with mild, moderate and severe forms of COVID-19 pneumonia (click here
Hydroxychloroquine is structurally related to Chloroquine (as the name implies) but is less toxic. It too acts an anti-infective and antirheumatic agent. It is used for rheumatoid arthritis, discoid and systemic lupus erythematosus and juvenile idiopathic arthritis
Another medication (not on this list) that is further along in clinical trials is Remdesivir, initially developed to treat Ebola virus (and, unfortunately, ineffective in Ebola) and developed by Gilead Sciences. It is now being tested on 761 patients in a study at multiple hospitals in Wuhan. The results from the trials are expected to be available over the next few weeks.
Lastly, I would add to this list Favilavir (Favipiravir). The National Medical Products Administration of China has approved the use of Favilavir, an anti-viral drug, as a treatment for coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial involving 70 patients.
There’s emerging evidence that some medications may have the potential to treat the symptoms of COVID-19. More large-scale testing is needed to determine if these treatments are safe and clinical trials for these drugs could take several months.
At this point in time, at Santa Monica Primary Care we are not recommending any change to patient’s current medications. Over the next weeks, however, we will be actively checking in with our patients to ensure that they have adequate supplies of vital medications. Based on data from France, we will begin to recommend Tylenol instead of Ibuprofen for supportive care of potential coronavirus infections. In the meantime, should you have questions or concerns, please feel free to call our office at (310) 828-4411. We are available 24/7 for our patients.