The COVID-19 pandemic has brought about a flood of information. Newspapers, television, social media and even the White House have resulted in an overwhelming amount of information that frontline first responders are sifting through as they try to understand the novel coronavirus and how they might care best for their patients. But it’s been really hard. Information and policies are constantly evolving, sometimes daily, and trustworthy sources of science have offered competing views of the truth.
This has led to what the World Health Organization terms an “infodemic” – and it’s critical that frontline workers receive the most factual information. Because of the nature of the pandemic, facts may evolve, and may be presented with limited certainty. This can lead to confusion and mistrust, throwing a damper on our efforts to contain the virus and limit it’s effects.
Social media and politicians have amplified mistruths, disinformation and conspiracy theories that have resulted in tragic deaths and likely amplified contagion spread. This article, at the time of writing, presents an analysis of experimental treatments that paramedics may encounter in the field or in conversation with patients, colleagues and friends. Because our knowledge, aided by research, is developing constantly, I’ll try to stick to the available science as of May 10, 2020, as analyzed with the best principles of evidence based medicine, while acknowledging that tenets of EBM include patient values and provider experience.
Let’s start with this: coronaviruses are tricky. Prior to COVID-19, there was no cure for the common cold, and despite experience in SARS and MERS, effective treatments and vaccines have eluded us. The best known RNA virus is perhaps influenza, which you’ve probably had at some point in your life. Antivirals for influenza are only weakly supported by evidence, and vaccines, which require tailoring annually, are less effective than childhood immunizations. What we know works for all viral illnesses is good supportive care, and, in the event of critical illness, best possible resuscitation and critical care practices like titrated oxygen, treating concomitant bacterial infections with antibiotics, and effective, protocolized sedation and mechanical ventilation.
Given the gravity of the COVID-19 pandemic, several experimental treatments have been proposed based on biological plausibility, our knowledge of RNA viruses, and observations from clinicians. At times, optimism has outpaced the evidence. Historically, rushing unproven therapies to patients outside of clinical trials has led to harms, with several promising treatments later proven to be harmful or useless (but costly).
Quinine medications have been used since the 17th century. Most famous for their antimalarial properties, quinines such as hydroxychloroquine have been used to treat Lupus and Rheumatoid arthritis. It has been hypothesized to disable SARS-CoV-2 by inhibiting its ability to enter human cells. In a February letter to the editor of the journal Cell, Chinese scientists reported that chloroquine was effective against SARS-CoV-2 in cells in a laboratory. A poorly designed and highly criticized study in 32 patients tested hydroxychloroquine, but without comparing it to another drug. Two randomized controlled trials found no difference when the drug was compared to routine care, and another study was stopped early for harm.
Complications of hydroxychloroquine use include long QT and fatal arrythmias. In overdose, seizures, depressed consciousness and fatal arrythmias has been observed. Regulators around the world have advised that hydroxychloroquine should not be used outside of trials, of which over 100 are currently underway.
Lopinavir (with Ritonavir)
Lopinavir inhibits a protease enzyme that prevents HIV from maturing to it’s infectious state. It is often combined, or “boosted”, with another protease inhibitor called Ritonavir that extends its duration of action. (You might see this written as LPV +r). An impressive RCT, launched Jan 18 and published Mar 18, enrolled 200 patients in China and found no difference. Further trials are underway. The most common side effect is diarrhea and can be hepatotoxic in overdose.
Remdesivir was released in 2014 as a potential Ebola virus treatment. By inhibiting replication of RNA viruses in laboratory studies, it was touted as a potential treatment for COVID-19. An RCT in Hubbei, China enrolled 237 patients and did not find a difference in viral loads, oxygen requirements, the need for mechanical ventilation or mortality.
An RCT funded by the US National Institutes of Health, with preliminary data released May 22, was reported to be effective in reducing duration of symptoms from 15 days to 11 days, but showed no difference in mortality. The benefits appeared to occur in people with earlier or milder disease, which makes sense; the drug blocks the virus from entering cells, whereas death is often from an inflammatory response to the virus that remdesivir is not designed to impact.
Because other trials have shown no benefit from remdesivir, it’s controversial as to who, if anyone, should receive the drug for COVID-19. On May 1, the FDA approved remdesivir for emergency use.
Overdose information is not available, but the drug is similar to acyclovir, which can cause GI and neurological symptoms in overdose.
Blocking the Immune Response
Several studies are investigating drugs that block the immune response to COVID-19, which can be thought of similar to the sepsis response to bacterial infection. Drugs that block interleukins, like tocilizumab, and JAK, like baricitinib, are approved for other indications and are hoped to be effective against the body’s own response to the virus. The use of convalescent serum, or which involves giving plasma from recovered COVID-19 patients to infected patients, is meant to provide infected individuals with antibodies to the virus that were developed by the immune systems of patients who have successfully fought off the virus. A very small trial of 39 patients who received convalescent plasma, who were compared to similar cases found in hospital records who did not receive the plasma, showed encouraging results that must be replicated in larger, controlled trials.
There are hundreds of SARS-CoV-2 trials underway currently, including major international studies that should better inform our treatments for COVID-19. Despite enthusiasm and pressure to rush cures to patients, our experience from prior outbreaks gives reason to pause and be cautious, and carefully but quickly study potential therapies using the scientific method.