NEJM editor-in-chief discusses the convergence of inflammation and infection in COVID-19 pathogenesis

Eric Rubin, MD
Eric Rubin, MD

Like most pathogens, SARS-CoV-2 causes disease not only by replicating in the host, but by its interplay with host inflammation. A growing understanding of the ways that COVID-19 is defined by the interface between the mechanisms that define infectious disease and rheumatology is contributing to advances in treatments and progress toward a vaccine, according to Eric Rubin, MD, editor-in-chief of The New England Journal of Medicine.

As someone at the forefront of new data analysis and dissemination, Dr. Rubin shared his unique perspective on the pandemic in his keynote address, COVID-19: The Convergence of Infection and Inflammation, during the ACR Convergence 2020 Opening Session on Thursday, Nov. 5. Registered attendees have on-demand access to watch a replay of the session through Wednesday, March 11.

When looking at the interplay between inflammation and infection as it relates to COVID-19 treatment, Dr. Rubin said that, given what is known about the pathogenesis of the disease, different approaches to intervention at different stages of the disease may be necessary.

“Early in disease, viral replication dominates. There’s a lot of replication occurring very early on—in fact, before people become symptomatic—and viral numbers tend to fall over the course of illness,” said Dr. Rubin, who is also professor and chair of the Department of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health. “There’s an inflammatory response, or an immune response, to the virus initially, followed by some sort of lull, and then an enhanced inflammatory response, which leads to the pathology late in disease. Given that, how can we intervene and make a difference?”

Thus far, he said, clinicians have a very limited number of treatment options.

“And those tools are really aimed at the virus itself, at preventing viral replication, which occurs early on in infection,” Dr. Rubin said. “A number of drugs have been tested in these circumstances, and we don’t really have anything that’s highly effective. Only one drug—the antiviral remdesivir—has been shown to have an effect. It has an effect on the clinical outcome of disease, but not much of an effect on death.”

At later stages of infection, however, he said that there has been some success with the use of corticosteroids, namely dexamethasone, to prevent the inflammatory response that occurs. 

“Corticosteroids are a class of drugs that we’ve used in many infections over the years, and we’ve used them with quite a bit of trepidation because we worry that viral replication will be increased by decreasing the appropriate inflammatory response to a viral infection. However, much of the pathology might be avoided,” Dr. Rubin said. “In the case of COVID-19 and the one large trial that’s been done, there was an effect of using dexamethasone in these patients late in infection. That effect was pretty small, but dramatic, because it reduced the number of deaths.”

While dexamethasone is not the only “anti-inflammatory” agent that’s being tested and being used in these circumstances, Dr. Rubin said it does have many advantages.

“We know how it works. It’s incredibly cheap and it’s widely available all over the world,” he said. “So, it’s set a standard that all of these other agents are going to have to beat.”

As research into COVID-19 treatments is conducted in laboratories around the world and a number of potential vaccines are in the pipeline, Dr. Rubin said the most important and proven effective interventions are the ones that can prevent infection in the first place.

“And we have many tools to do that. For example, masks—we know that those work. Social distancing, spreading out from people also is important. Isolation of infected people and quarantine of exposed people,” he said. “And finally, testing followed by contact tracing so that we can make sure that we’re isolating and quarantining the appropriate people to try to shut down spread. I want to emphasize how important these straightforward, simple public health measures are.”