Q&A: Navigating ‘the COVID literature tsunami’
As COVID-19 continues to surge across the United States, researchers have been analyzing developments to determine what areas of research should be explored next.
In a recent journal article, Ferric C. Fang, MD, professor of laboratory medicine, pathology and microbiology at the University of Washington, and other editors of Clinical Infectious Diseases explored previous research related to COVID-19 virology, epidemiology, presentation, diagnosis, complications, treatment and prevention and summarized the results from several related studies to help researchers and clinicians “surf the COVID literature tsunami.”
Healio spoke with Fang about the state of COVID-19 diagnostic and vaccine research, and the role of peer-reviewed studies during the pandemic.
What takeaways from this summary are most important for clinicians?
We have now learned enough about COVID-19 to provide effective supportive care for the majority of patients with severe illness, provided that health care systems are not overwhelmed. In the sickest patients, we have learned that it is an overly exuberant inflammatory response, not direct actions of the virus, that is causing the most damage. This tells us what we need to do to prevent further harm. We also now understand enough about the epidemiology of COVID-19 to understand who is at greatest risk and how to effectively limit community spread, if we have the will to work together as a society and take appropriate measures.
What areas of COVID-19 research (vaccines, diagnostics, etc.) have evolved the most rapidly during the pandemic? Why do you believe these evolved faster than other areas?
After a slow start out of the gate, COVID-19 diagnostics have evolved rapidly, although there continue to be issues with supply chains that are preventing more widespread implementation of testing at some locations. With regard to therapeutics, we have learned that large centrally coordinated clinical trials such as the RECOVERY trial in the United Kingdom tend to be more valuable than retrospective observational studies and multiple fragmented small trials. Unfortunately, many of the answers, such as the lack of efficacy of hydroxychloroquine, have been negative, but it is also important to know what doesn’t work. Thanks to RECOVERY, we now know that dexamethasone is beneficial in critically ill patients requiring ventilatory support, something that was by no means a certainty at the outset of the pandemic. Novel adaptive trial designs can quickly evaluate multiple agents and combinations of agents, as has been demonstrated in the NIH-sponsored ACTIV studies. Vaccine development has actually progressed remarkably quickly. We are still awaiting the most important results of these trials because it simply takes time to properly organize and execute a rigorous clinical trial of a vaccine. As the punchline to an old joke goes, the immune system is very complicated.
Conversely, what areas of research need more exploration?
COVID-19 exhibits enormous variability in severity among individuals and countries. We grasp some of the outlines of reasons for this variability, such as age, sex and comorbidities, but there is much that we do not understand. For example, what is the influence of prior exposure to endemic seasonal coronaviruses? There is evidence that prior exposure may be associated with milder illness, but other observations suggest the potential for detrimental cross-reactive immune responses. Another important issue to understand is the impact of viral inoculum on clinical outcomes. Could it be that more recent cases of COVID-19 are less likely to be fatal because people are being infected by lower doses of virus as a result of social distancing and face masks?
A third issue that urgently requires clarification is how to safely reopen communities without overwhelming health care systems and causing terrible morbidity and mortality in high-risk persons. This is presently the $64 million question. In theory, we should be able to keep viral spread at a manageable level without costly sustained lockdowns if we can avoid superspreading events, but that is easier said than done.
What advice do you have for clinicians in regard to navigating the amount of peer-reviewed articles related to COVID-19?
This is an enormous challenge, and the Clinical Infectious Diseases editors wrote this article in part to help busy clinicians stay informed about some of the most significant recent publications. Personally, I devote a large portion of each weekend to surveying the past week’s literature and trying to keep up. I have a personal reference collection that now exceeds 1,200 key articles and a set of single-spaced notes about those articles that exceeds 40 pages.
What do you believe will likely be the next major development in regard to COVID-19 research?
We are all looking forward to hearing about the effectiveness of SARS-CoV-2 vaccines currently undergoing clinical evaluation, perhaps as soon as the next couple of months. Although many are pinning their hopes on vaccines to ultimately get us back to the way things used to be, the complexity of vaccine development should not be underestimated. As in the case of HIV, highly effective and widely available oral anticoronavirus drugs might also prove to be game changing while vaccine development proceeds.