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Anti-viral Medications for COVID-19: The future for investigational, existing anti-viral or a combination approach to help stem this pandemic

Getting to know what a virus is, how it works, and how it invades will help us understand how to stop it. 

Please note: This article has been updated on April 15, 2020

Getting to know what a virus is, how it works and how it invades will help us understand how to stop it. A virus is very small. It is 0.001 to 0.1 microns which is 100 times smaller than a bacteria cell. A virus is genetic information, a single strand RNA, in a spiked protein capsule that invades and uses a body cell’s protein, energy stores and genetic material to replicate a new virus. A person coughs and droplets with the virus spreads by direct contact to the face. This is called the T-zone (T for touch). T zone areas of infection are the eyes, nose and mouth. To put it in aviation terms, it is the virus touchdown zone. Your hands are the vehicle of the virus to the entry points. The virus invades, replicates and spreads to the lung tissue cells where it causes inflammation, damage and mucous production. This is called Acute Respiratory Distress Syndrome (ARDS). The patient will often go into septic shock, causing a very low blood pressure which subsequently leads to very little oxygen getting to the lungs.

COVID-19 means it is a coronavirus (corona meaning crown) identified in 2019. It comes from a virus called SARS-CoV-2 (Severe Acute Respiratory Syndrome) coronavirus discovered in 2002. This virus (SARS 2002) originated in bats, spread to civets (cat in China) and later was spread to humans. SARS 2002 reported 8,098 cases and caused 774 deaths at a rate of 9.6%.

 Another coronavirus called MERS (Middle East Respiratory Syndrome) 2012 originated in bats, spread to camels and then to humans resulting in a reported 2,494 cases with 858 deaths, at a rate of 34%. COVID-19 has been speculated to have originated in bats, spread to pangolins (cross of an anteater and armadillo) and later to humans. Pangolins are a delicacy for their meat in China, and their scales are used as a folk medicine. As of April 14, 2020, there have been 579,005 cases reported with 22,252 deaths, at a rate of 3.8%. This data comes from the CDC.  

Once the patient is infected there is an incubation period between 5 to 24 days. Symptoms are usually seen at 5 days, but as you can see, symptoms in some patients may not be seen until much later. There are asymptomatic patients who do not show any signs and symptoms. This is probably due to a very low viral load of COVID-19. It is now known based on recent studies from the CDC, that asymptomatic patients can spread the virus. Asymptomatic patients with COVID 19 and patients who are infected that may later show symptoms can spread COVID 19 between people who are in close proximity to each other. The recommendation is to wear a cloth mask when going to the grocery store and pharmacy and stay 6 feet from each other

There is also a replication quotient called Ro (R naught) which indicates how quickly the virus spreads. If the Ro is 1 that means one patient can spread to one patient. COVID-19 has a Ro of 2 to 2.5, which means one infected patient can spread the virus to a least 2 other people. This will lead to a geometric increase in infected patients.

Besides coughing and sneezing spreading the virus, it has been postulated the fecal route may also be a way of transmission. There have been cases in China involving a faulty drainage system where the COVID-19 was spread from toilet to sink to patient, resulting in infection. The virus resides in blood and has also been isolated in stool (this may be the reason for the toilet paper shortage)!

What is in our anti-viral toolbox that can be used to eradicate COVID-19? Since the end of 2019, I have been researching this on a global scale. My way of thinking is we have anti-HIV and anti-influenza medications that have been proven to work on virus. The World Health Organization (WHO) has taken a very close look at a global database of all available anti-viral medications. WHO has found 120 medications, already on the global market that has been shown to be safe to give to humans. Of these 120 medications, 31 were identified as potential candidates for prophylaxis and treatment of coronavirus infections. An international collaboration of hundreds of scientists around the world, including microbiologists at Mount Sinai hospital in New York and the Pasteur Institute in Paris have identified 50 medications to be tested. Some of these medications are used in cancer treatment.  They mask the proteins that are needed by COVID-19 to replicate. Randomized controlled and observational trials will need to be done to validate if these medications can be used successfully. Per NIH, U.S. National Library of Medicine, clinicaltrials.gov, there are 585 trials, studying various treatments for COVID 19. I have also found at least 8 partnership (2 separate companies working together) pharmaceutical companies working on vaccines. The vaccines take longer to get to market and they are not expected to be out until the summer of this year at the earliest.

A study was published on February 4th, 2020, Cell Research (2020) 30:269-271, that came out of China looked at 5 anti-viral medications in vitro, against COVID-19. In vitro means the process is performed in a test tube, culture dish or elsewhere outside a living organism. A new anti-viral medication called Remdesivir and an antimalarial medication called chloroquine were added to a broth of COVID-19 and this combination stopped the replication of the virus. Remdesivir stops the genetic material of the virus from replicating.

On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever. He disclosed that he had returned to Washington State on January 15 after traveling to visit his family in Wuhan, China. On the evening of Day 7 of hospital admission, he received IV Remdesivir. The patient received Remdesivir for “compassionate use” from China.  The next day he was off supplemental oxygen and his pneumonia improved, (First Case of 2019 Novel Coronavirus in the United States, March 5, 2020 N Engl J Med 2020.

In a study out of Wuhan, China, 41 patients with pneumonia from COVID-19 were treated with traditional antibiotics, and 38 (93%) with an oral anti-viral influenza medication, oseltamivir (TamifluÒ). A randomized controlled trial of two anti-HIV medications, ritonavir and lopinavir has been initiated to assess the efficacy in patients hospitalized with COVID-19 (Lancet Volume 395, Issue 10223, P497-506, February 15, 2020.

I am very grateful to see the world coming together to share their resources, wisdom, experience and research to take care of patients now and create a future vaccine with COVID-19. Pilots are a very mobile group of people. Continue to do your hand washing, exercise, eat well and keep a 6-foot distance between you and folks who are coughing and sneezing. AOPA recommends not to fly internationally with general aviation aircraft, so as to slow the spread and risk of being infected. Your airplane makes a wonderful incubator for viruses. I also recommend wiping down all rental aircraft inside before flight. If renting, ask what the FBO is doing to decrease the risk of infection with COVID-19. Make sure your daily information about coronavirus is coming from the CDC and WHO. That is my go-to site. Stay well everyone.

Larry M. Diamond, PharmD, CFII

Larry Diamond has a Doctor of Pharmacy Degree and has been a pharmacist for 37 years. Larry’s pharmacy practice has been as a Clinical Pharmacy Specialist in Cardiology, Orthopedic Surgery Specialist and most recently Clinical Pharmacy Coordinator. He is a CFII, a pilot for 33 years and has been an AOPA member since 1984.

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