Intersection of ‘highly heterogenous’ COVID-19, IMIDs remains ‘poorly understood’
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Scientific advancement has yielded slow but steady progress in the understanding of COVID-19, particularly in patients with immune-mediated conditions, a presenter said at the Basic and Clinical Immunology for the Busy Clinician symposium.
“COVID-19 merits a serious place in the pantheon of pandemics,” Leonard Calabrese, DO, RJ Fasenmyer Chair of Clinical Immunology at Cleveland Clinic, said in his presentation.
Calabrese provided a brief overview of the political and social challenges presented by COVID-19 before ultimately focusing on the role science has played in combating the pandemic.
He suggested that the nearly 6 million deaths is a “gross underestimation” of the actual impact that the virus has had. More troubling has been the popular response, particularly in political arenas and on social media. “You can see how woefully unprepared we are for this,” he said.
However, as he has mentioned in similar talks over the last 2 years, Calabrese highlighted the body of work that the scientific community has mounted with cautious optimism. Specifically for rheumatologists, COVID-19 has placed a spotlight on immune-mediated diseases like never before. With that light shining, the challenges are taking shape.
“The intersection of viruses and immune-mediated disease still remains poorly understood,” Calabrese said. Specifically, the “highly heterogeneous” nature of COVID-19 itself has made it an elusive target.
That said, clinicians have been able to hit some targets. Calabrese suggested that in broad, general terms, there is a reliable treatment paradigm for COVID-19. “Early on, we are bolstering antiviral defense,” he said. “In the later stage, we are using immunomodulatory therapies, led by dexamethasone.”
Calabrese described the success of dexamethasone in the immune-mediated COVID-19 setting as an unexpected turn, as the drug is generally avoided in patients with these conditions. “It is surprising that dexamethasone has saved this pandemic,” he said.
But more work needs to be done to refine treatment approaches. “We lack useful biomarkers,” Calabrese said. “So far, AI and mechanical learning have generated thousands of papers on this, but nothing we use at the bedside.”
It is not just machines that are creating data. The speed and advancement of scientific literature on COVID-19 is a good news/bad news proposition, according to Calabrese. There have been some 250,000 peer-reviewed papers published since January 2020, with 18,000 currently under peer review, and more than 4 million COVID-19-related hits on Google. He has no illusions that it will be easy to make sense of all of this information, but he urged attendees to try to digest as much of it as possible. “We have to adapt to this,” he said. “We can’t fight it.”
Calabrese highlighted a couple of key clinical and research challenges for the coming months and years. One is to understand the role of the interferon pathway in some patients who experience severe COVID-19. Another is the production of anti-COVID-19 autoantibodies in certain individuals over aged 70 years. “This is an evolving story,” he said.
Yet another challenge for clinicians is to understand what happens in both the upper and lower respiratory tracts as the virus progresses. “There are still many unknows about this, as well,” Calabrese said.
Further downstream, Calabrese believes that individuals experiencing “long COVID” symptoms may become a formidable patient population. “That is our next major health challenge,” Calabrese said.
“The final question, of course, is: how will this pandemic end?” he said. “No one really knows.”
While the end is uncertain, the near future is clear, according to Calabrese. “COVID-19 is not going to disappear,” he said. “This virus is with us now. It is part of the fabric of humanity.”
Like many experts, Calabrese expressed a reasonable and rational hope that the virulence of the virus will diminish with each variant. “But we don’t know,” he said.
In closing, Calabrese offered a stark portrait of the current moment. “We have two pandemics,” he said. “There is one in the healthy and vaccinated. But the second is in the immunocompromised and unvaccinated.”
Calabrese acknowledged that unvaccinated populations are, in some ways, a separate issue from the one facing rheumatologists each day as they manage their patients with immune mediated diseases. But as for those patients, he was clear about the work that needs to be done. “We have a long way to go.”
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Calabrese L. COVID-19 at 2 years: politics, science and challenges. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 26, 2022. (virtual meeting).
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