Novel Coronavirus 2019 (COVID-19)

Medications and Treatments for COVID-19

LAU’s School of Pharmacy clinical faculty discuss current treatments for COVID-19 and the protocol for researching a new medicine.

Clinical Associate Professor-Pharmacy Practice in Infectious Diseases, Hanine Mansour (PharmD ‘02), and Clinical Assistant Professor-Pharmacy Practice in Critical Care, Yara Mary Kuyumjian (PharmD ‘14) clear up fundamental questions on the pharmaceutical side of COVID-19.

When a patient is diagnosed with COVID-19, what kind of treatment does he/she get at the hospital?

Currently, there is little firm evidence of a single or a combination of medications to treat or cure the 2019 coronavirus disease or COVID-19 that is caused by the novel coronavirus. Depending on the severity of the illness and the patient’s coexisting diseases, the in-hospital treatment of a patient with confirmed COVID-19 can range from supportive and symptomatic treatment to more advanced therapies that target the virus. Globally, there are currently many clinical trials investigating different treatment regimens for COVID-19 including existing medications such as chloroquine and hydroxychloroquine that are typically used for the treatment of malaria and rheumatologic diseases, antiretrovirals for the treatment of HIV/AIDS, the anti-viral agent remdesivir, and the immunosuppressant tocilizumab that targets the over-reactive immune system.

Lately we’ve been hearing on different media channels that there are medications proven effective in the treatment of COVID-19. Is this true?

This is in relation to chloroquine and hydroxychloroquine (a less toxic derivative of chloroquine). What initially piqued curiosity in considering these two medications for the treatment of COVID-19 is their in vitro (laboratory experiment outside living organism) activity against its causative agent the Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The media hype around this was further ignited following the results of a small-scale pilot non-randomized clinical trial in France on COVID-19 positive patients that used a combination of hydroxychloroquine 600 mg per day with or without azithromycin (an antibiotic) 500 mg on day one followed by 250 mg per day for the following four days depending on the patient’s clinical condition.

A total of 26 patients received hydroxychloroquine alone, and six patients received azithromycin in addition to hydroxychloroquine. Study results showed that, compared to untreated COVID-19 positive patents, hydroxychloroquine-treated patients had clearance of the nasopharyngeal virus in 3-6 days with possible added benefits when hydroxychloroquine and azithromycin are combined.

Furthermore, the same group of investigators followed up with another similar trial on 80 patients. Sixty-five out of 80 patients (81 percent) had favorable outcomes and were discharged from the hospital on day four, one patient died, and treatment was stopped in one patient due to cardiac side effects. Nasopharyngeal tests showed that the majority of patients’ nasopharynx cleared from the virus on day eight, and in all patients on day 12.  Although these results are promising, the trial did not have a control arm and there remain concerns regarding the real effect of medications on the overall clearance of the virus.

Because small-size trials cannot provide the needed evidence of the newly examined medications, there are ongoing large trials such as the World Health Organization (WHO) SOLIDARITY trial that is aimed at evaluating the safety and efficacy of the different treatments that may have shown potential benefit in smaller studies. Furthermore, the US Food and Drug Administration (FDA) has issued most recently a guidance letter for the emergency use authorization of hydroxychloroquine and chloroquine in COVID-19.

While there is uncertainty surrounding the evidence supporting the use of antimalarial medications for COVID-19, the evidence for the use of these drugs to treat immune-mediated diseases is established. For example, hydroxychloroquine is a cornerstone of therapy for patients with systemic lupus erythematosus or SLE. The irresponsible stockpiling of these medications may lead to their shortage, eventually depriving patients with SLE, rheumatoid arthritis or other conditions for which they have proven benefits.

Hence, physicians and pharmacists need to adhere to the highest standards of practice whenever prescribing or dispensing hydroxychloroquine or chloroquine with the intent to stockpile these medications. The public is reminded that these medications are not used to prevent or to self-medicate COVID-19 and can have serious side effects. Although they are overall well tolerated (hydroxychloroquine more so than chloroquine) and have been used for decades for established indications, they can have psychiatric and cardiac side effects such as life-threatening irregularities in the heart rhythm, and can also cause a drop in blood sugar levels particularly in diabetic patients. Additionally, azithromycin can negatively affect the heart and potentially more dangerously so when combined with hydroxychloroquine or chloroquine. Therefore, this combination should only be used when properly justified in COVID-19 patients and under close medical supervision.

In the setting of outbreaks caused by new viruses such as this 2019 novel coronavirus, what are the procedures for researching available medicines that might treat it? Can investigational agents be used on patients with the disease before going through clinical trials?

When considering clinical research during rapidly emerging outbreaks, it is typical that medicinal products that have previously shown promise in the earlier pre-clinical testing stages are pushed to the forefront of clinical trials. As COVID-19 is progressing rapidly, scientists and clinicians have begun to investigate the potential role of antivirals that are still in their earliest stages of development.

For instance, remdesivir is an antiviral that was originally developed for the treatment of Ebola virus disease but has not been labeled by the FDA for such treatment. The potent in vitro antiviral activity of remdesivir has also been demonstrated against the Middle East Respiratory Syndrome (MERS-CoV), SARS-CoV-1, and SARS-CoV-2 the virus responsible for COVID-19.

Remdesivir’s high selectivity for the virus makes it a potentially safe medication. Considering its remarkable effects in vitro and laboratory animal models, remdesivir has been made available by the pharmaceutical manufacturer to clinicians through a compassionate “expanded access process” and is being investigated in COVID- 19 patients. This process allows access to investigational therapies outside clinical trials when no comparable or satisfactory alternative therapeutic options are available. However, it is important to note that randomized controlled trials remain the gold standard type of studies to assess the efficacy and safety of medication therapies.

Since a lot of information is coming out these days, some fake and some true, what is the procedure and who is the authority when it comes to announcing new medications/effective treatments to the public?

It is always wise to get medication information from reliable sources such as the FDA, Centers for Disease Control and Prevention (CDC), European Medicines Agency (EMA), or WHO. In Lebanon, people can also follow the updates on the Ministry of Public Health webpage. It is also important to discuss medication directions with the treating physician or pharmacist.

How is the vaccine development going for COVID-19?

There are about 35 companies and academic institutions working to develop such a vaccine. Few have completed the testing on animals and proceeded to clinical trials to test on humans in China and the US. The fast development happened when China shared the sequence of genetic material of SARS-CoV-2. As this is a new pathogen in humans, only a few technologies to build the vaccine have been tested. This will be the first vaccine made from genetic material – RNA or DNA – to be approved, if this happens.

Also, clinical trials are a long process and take place in three phases. In the first phase, the product is tested on a few dozen healthy volunteers for safety while monitoring for adverse effects. The second involves hundreds of people, and in this case, will be conducted in affected parts of the world to determine the effectiveness of the vaccine. The final phase tests are much the same as in phase two, but are carried out on thousands of people. These are only some of the reasons why developing the vaccine will take time and cannot happen quickly.

Can immunity against the virus be potentially transferred to sick patients from those who have recovered from COVID-19?

Potentially yes, but we do not know yet for how long this immunity lasts in recovered COVID-19 patients. “Convalescent plasma” (plasma is the liquid blood component) is being investigated in seriously ill COVID-19 patients. The blood of a recovered patient from COVID-19 contains specific antibodies to the coronavirus. The antibody-rich plasma after separation from the whole blood is then transfused into a very sick COVID-19 patient to help fight the viral infection.

Convalescent plasma has been explored in other outbreaks such as the 2009-2010 H1N1 influenza, 2003 SARS-CoV-1, 2012 MERS-CoV and 2014 Ebola virus, all of which showed variable outcomes. While awaiting the results of ongoing clinical trials, it is not yet officially recommended to use convalescent plasma in COVID-19 patients. Yet, given the urgent need for therapeutic options, the FDA has a facilitated process for physicians to access and use convalescent plasma in COVID-19 patients with serious or immediately life-threatening disease.

While this novel coronavirus pandemic is rapidly changing, treatment guidelines can also quickly change. Therefore experts should be regularly consulted on up-to-date recommendations.