The current SARS CoV-2 pandemic has, understandably, instilled a palpable degree of anxiety, uncertainty, and fear throughout our cities and indeed throughout the globe. Naturally, what follows are intense hopes of modalities that can identify, prevent, treat, or even cure and eradicate this pervasive pathogen. Here, we will provide a brief synopsis of what is currently being researched, what is available, and our position on where these modalities stand as of this writing. Please note that virtually every aspect of this virus and the disease it causes changes day to day as we learn more. Lastly, we absolutely encourage self-education as knowledge really is power, however, in the age of free flowing internet, we caution that it can be challenging to separate quality from potentially inaccurate information.
A complete list of medications being investigated are beyond the scope of this article so we will focus on the few that have made headlines.
Hydroxychloroquine: By far the drug receiving the most press currently. This drug, along with its close relative chloroquine, has been used for many years for the treatment of autoimmune diseases and malaria respectively. Its recent off-label use for patients with covid stemmed from observations made in the laboratory setting that these drugs appear to have antiviral and immunomodulatory properties on cells. Additionally, a couple of very small uncontrolled studies as well as various anecdotal reports of use suggested an improved outcome for COVID-19 when taking these drugs alone or in combination with azithromycin, a macrolide antibiotic. However, much larger and more recent randomized studies that controlled for many factors have not demonstrated significant benefit in hospitalized patients taking either of these drugs alone or in combination with Azithromycin. This drug carries the potential for significant adverse effects related to the heart, eyes, and insulin levels and has a very long half life. For these reasons, the risks and benefits must be weighed prior to use. We believe that there is still much potential to study the use of this drug, especially in the outpatient setting. If safety and efficacy are ultimately demonstrated then we feel this could be a great tool in the fight against COVID-19.
Remdesivir: This investigational antiviral, which has already been approved for Emergency Use Authorization in the US and for full use in Japan for the treatment of COVID-19, is also being heavily studied and has shown potential due to promising results and low incidence of adverse effects. To date, 3 randomized, controlled clinical trials have demonstrated a modest improvement in clinical outcome in both moderate and severe disease, with the latest research showing a 5 day course as being as equally effective as a 10 day course. Demonstrated improvements have so far been significant but not dramatic. Future trials may be more revealing. Given its overall safety profile, we will continue to monitor these future studies along with its potential for use in treating COVID-19.
Convalescent plasma and Monoclonal antibodies: A more novel approach to treating COVID-19, both of these modalities involve introducing antibodies that attack SARS CoV-2, whether by harvesting from those who already recovered from the virus or through synthetic production. This technique had already shown very promising results and success with the Ebola virus in the past and trials are currently underway with the novel coronavirus. Although this exciting new approach also has great potential, it is currently not known how long these antibodies will last once infused and subsequently, how long immunity will last. We will keep a very close eye on these developments.
Dexamethasone: Although steroids were initially not recommended for patients with COVID-19, A recent unpublished large randomized study conducted in the UK demonstrated significant reductions in mortality to hospitalized patients with severe infection requiring supplemental oxygen with the greatest benefit observed in those requiring mechanical ventilation. There was no benefit observed in patients who did not require supplemental oxygen. The Patients with severe infection develop a severe inflammatory response which results in severe lung injury and multi-system organ failure. Steroids are highly potent anti-inflammatory agents which may mitigate the immune response seen in patients with severe disease. There is no evidence to suggest its usefulness in the outpatient setting and indeed it may be harmful through its immunosuppressive mechanism.
This appropriately brings us into our next hot topic. The availability of this type of testing has generated a lot of excitement and hope, and as promising as this is, it is also critical to understand how these tests work, what they might tell us and what they may not….yet. The current tests which are available detect up to 3 different types of antibodies depending on the specific test chosen. All 3 are produced at varying intervals anywhere from 1-3 weeks after infection, with IgM and IgA generally appearing earlier on, and IgG being produced a bit later and persisting for much longer. There is some evidence to suggest that the more severe the infection and the more robust the immune response, the more IgG is produced and the longer it may last to potentially offer greater and longer protection. While there is much uncertainty regarding how to use the results of these tests clinically, we are most certain that a positive test likely indicates prior exposure or infection. If IgM is positive, with or without IgG, there is a chance one is still actively infected. If IgG is the only detectable antibody, it is likely that a person is no longer infected but was in the past and implies the person has some level of protection against reinfection. It has also been suggested that the possibility of false positive results exist as there is a chance that the test is cross reactive to prior infections with other coronaviruses responsible for some common colds. What we do not know at present time is whether the presence of these antibodies indeed confers complete immunity and if so, then for how long. Studies on the prior SARS virus of 2003 showed persistence of neutralizing antibodies for 2 years on average with a decline soon after. Several other coronaviruses responsible for common colds showed an average of immunity for 3 months to just under 1 year. A new, small study in China suggested that patients with COVID-19 who never developed any symptoms may no longer have any detectable antibodies in as little as 2 months due to a lack of a robust immune response to the virus. Future research is focusing on the persistence and relevance of these antibodies following infection with SARS CoV-2, as well as tests to identify a recently discovered antibody to what is known as the Receptor Binding Domain (RBD). This antibody is more specific to the neutralization of a virus and a better marker of immunity. Lastly, there are other factors involved in being immune to further infection with a pathogen than antibody generation. We all hope to learn more soon.
Although there are no formally approved medical treatments for COVID-19 as of this writing, there are several that hold some promise and many more that are being investigated which are beyond the scope of this article. It is important to note that this virus was completely unknown to us only several months ago and the systems we have in place in this country to ensure that a proposed treatment’s safety and efficacy outweigh any of the potential risks follow a long and rigorous process. We want to ensure that all of the checks and balances remain in place and aren’t sacrificed to well founded fear and panic, but it appears that the sense of urgency is also having a positive effect on the consideration and expediting of the research and approval of effective treatments for this pandemic. We may be facing this virus for a while but we are confident that research will bear fruit to fight it effectively in the near future.