Therapies for COVID-19

Life in the Time of Coronavirus - Brought to you by Dr. TZ

As the COVID-19 pandemic progresses much attention is being paid to possible therapies. This article reviews what is currently happening as we attempt to treat current patients while at the same time accumulating data necessary to make sound scientific and medical decisions on what truly works.

The antiviral drug remdesivir was first used in the U.S. for the first patient diagnosed in Washington State on January 19, 2020. It was obtained as a compassionate release (expanded-access) medication, a method that allows a company to release an unapproved drug for clinical use. In return, the treating physicians must provide data to the company for the company’s FDA drug file. That first patient survived and his physicians thought the drug made a clinical difference. However, thinking the drug made a difference is far from proof that it did make a difference. Since then research trials have begun in China, the U.S., France, and Norway. Most are randomized clinical trials (RCT), meaning that the drug under study is compared in humans with either standard-of-care treatment or another drug. One of these trials is being conducted by Kaiser-Permanente. There are also a few expanded-access trials open, including one at Huntington Memorial Hospital in Pasadena. Because expanded-access trials lack a comparison group, they are much less valuable in assessing real differences between remdesivir and the standard-of-care.

 The “hot” drug in the news at present is hydroxychloroquine (HCQ). This drug has been approved in the U.S. since 1955 for use as an antimalarial and also to control autoimmune diseases such as lupus and rheumatoid arthritis. Clinicaltrials.gov has 54 registered trials with 12 of them actively recruiting subjects in RCTs. One study from France has been promoted widely in the news.  However, that study is full of faults and biases and is simply anecdotal. There is one completed trial from Shanghai that had 30 subjects with COVID-19; half received HCQ and half did not. I read the abstract (the paper is in Chinese): there were no statistical differences in the outcomes between the two groups. Henry Ford Hospital in Detroit is launching an RCT to determine whether HCQ prophylaxis may prevent infections with SARS-CoV-2; that trial was slated to begin on April 6. Hydroxychloroquine may be a useful therapy but, in the absence of proof, use of this drug depends on hope rather than science. Because it is already FDA approved, some hospitals (such as Massachusetts General Hospital) have issued guidelines for when it should be used in the clinical setting for COVID-19 patients. Data collected from ad hoc use of the drug in individual cases will be extremely hard to analyze.

HCQ is being considered for use in COVID-19 because, over 10 years ago, its cousin, chloroquine, was shown to inhibit the replication of SARS-CoV-1, the cause of the SARS epidemic in 2002-03. Subsequent study suggested these drugs could also inhibit the ability of the virus to infect human cells. HCQ is also a known modulator of the immune system that down-regulates the immune response. This is a fancy way to say it “puts on the brakes” and lessens the possibility that the immune system will overreact to COVID-19. Such overreaction, known as cytokine storm, causes severe lung and other organ damage, leading to the need for intubation and mechanical ventilation in an ICU. The end result of cytokine storm is often multisystem organ failure where not only the lungs, but the kidneys, the liver, the heart, and the brain fail, leading to death. The theoretical good that any drug has must always be balanced against harms it may cause. HCQ has the potential to induce lethal heart rhythms (especially in critically ill patients taking other drugs), retinopathy, and neuropsychiatric symptoms and its use in those with diabetes and other serious diseases require close monitoring. Hence, the need for thorough RCTs to provide those answers in a closely monitored setting.

 Preformed antibodies (immune plasma) from patients who have survived COVID-19 are also entering clinical trials. This kind of therapy dates back to Emil Behring in 1891 Germany (he received the Nobel Prize) and his work against diphtheria. Immune plasma has already been used in a few clinical instances. Three U.S. firms have RCTs set to begin this summer. The hope is to manufacture a hyperimmune plasma preparation that would be easily administered to COVID-19 patients.

 Finally, research is underway to find other drugs to prevent the cytokine storm associated with this disease. Trials with monoclonal antibody preparations used in people with rheumatoid arthritis and inflammatory bowel disease are pending in the U.S. with one such trial underway in France, to ascertain if cytokine storm can be prevented in patients with severe COVID-19 disease. Other drugs that inhibit cytokine storm, repurposed from oncology, are also pending trials. All need RCTs to assess for safety and efficacy.

There are many excellent minds at work gathering the clinical data to decide which therapies work best and in which subset of COVID-19 patients. In the setting of a pandemic, which may last for many months until an effective vaccine is developed, performing RCTs to make decisions on treatments is essential. Science and expertise are what will help humanity overcome COVID-19.

Feel free to send questions and concerns about COVID-19 and this pandemic to healthcare [at] LWV-PA.org.  They will be collated and addressed in future columns; individual answers to individual questioners will not be provided. Please stay safe and don’t forget to wash your hands, stay 6 feet away from others, wear your mask in public, and, as much as humanly possible, don’t touch your face.

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