‘Real alliances’ between immunology, rheumatology provide hope for COVID-19 therapy
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The intersection of immunology and rheumatology may be a fruitful source of information regarding COVID-19 therapeutic possibilities and vaccine development, according to the keynote speaker at ACR 2020.
“Inflammation is an integral part of what can cause infection,” Eric Rubin, MD, PhD, editor in chief of The New England Journal of Medicine, and of the department of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health. He suggested that there are “real alliances” between infectious diseases and immunology — his areas of expertise — and rheumatology.
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The “interplay” of inflammation and immune response can vary from infection to infection, according to Rubin, who added that this interplay was brought into “sharp relief” by COVID-19.
The keynote talk included an overview of variables pertaining to the phases and complications of COVID-19 infection. Rubin said a deeper understanding of the inflammatory phases of the virus may unlock clues to both treatment and vaccine development.
SARS-CoV-2 has a “bimodal distribution” of inflammation, according to Rubin. This plays out clinically as an initial inflammatory or immune response, then a lull, then an enhanced inflammatory response that may lead to more severe disease or death later.
Before addressing how understanding of these inflammatory factors may inform treatment paradigms and vaccine development, Rubin stressed that simple public health measures to prevent infection work. “The easiest place to intervene in COVID-19 is before infection occurs,” he said. “Masks: We know that they work.”
Social distancing also is effective, as are quarantining and self-isolation of infected and potentially infected individuals and rigorous testing followed by contact tracing.
But Rubin acknowledged that therapeutic interventions and a vaccine will ultimately be necessary to contain COVID-19. However, developments on that front are slow. “Only remdesivir (Veklury, Gilead Sciences) has been shown to have some effect,” he said. While the drug has demonstrated some clinical outcome, it has demonstrated “not much” effect on mortality due to COVID-19.
But it is not all bad news. Corticosteroids, including dexamethasone, have demonstrated efficacy in preventing the second stage of inflammatory response. But Rubin stressed that clinicians use this drug with “trepidation” because it can lead to increased viral replication.
The key argument in favor of steroids is that the effect has the “small but dramatic” outcome of reducing mortality. There are other advantages to dexamethasone, as well, according to Rubin. “We know how it works, it is cheap and it is widely available,” he said.
Turning to vaccine development, the biggest challenge facing the research community is simply time, according to Rubin. “We are shrinking the usual time [for developing a vaccine] from a decade to a matter of months,” he said.
As for good news on the vaccine front, while a safe version of the SARS-CoV-2 virus is not yet available for use in a live vaccine, a live attenuated vaccine may be possible.
Another promising approach is to take some parts of the virus, purify them and use them in the vaccines. In the case of COVID-19, researchers have largely been using the spiked glycoprotein. “But we do not know that this antigen, or any antigen, produces effect in humans,” Rubin said.
Perhaps the most promising area of COVID-19 vaccine development is in the microRNA products moving through clinical trials. While mRNA vaccines were historically unstable and unable to replicate, Rubin noted that these problems have been overcome by technology in recent years.
As the research community addresses these important clinical questions, Rubin stressed that the real test of a vaccine is simply time. “When do you know a vaccine is safe?” he said. “The answer is not so simple. There is no magic formula for knowing if it is safe.”
Once a product or products hit the market, researchers will conduct “event-driven trials” in which experts “wait for a number of infections to occur and see how they play out,” Rubin said. Analysis of who received the vaccine and who received placebo will provide the key efficacy numbers. But that is still in the distance.
The silver lining in all of this is that it may not be necessary to make a choice about the type of vaccine that is ultimately used. “It is likely that if we have one vaccine, we will have multiple,” Rubin said.
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Rubin E. Keynote: COVID-19: The Convergence of Infection and Inflammation. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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