The intersection of ‘very heterogeneous’ COVID-19, IMIDs remain ‘poorly understood’
The intersection of ‘very heterogeneous’ COVID-19, IMIDs remain ‘poorly understood’

The intersection of ‘very heterogeneous’ COVID-19, IMIDs remain ‘poorly understood’

March 2, 2022

3 min read


Calabrese L. COVID-19 in 2 years: politics, science and challenges. Presented at Basic and Clinical Immunology for the Busy Clinician; February 26, 2022. (virtual meeting).

Information: Disclosures: Calabrese does not report any relevant financial information.

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Scientific advances have provided slow but steady advances in the understanding of COVID-19, especially in patients with immune-mediated conditions, said a speaker at the Basic and Clinical Immunology for the Busy Clinicians symposium.

Leonard Calabrese, DO

Leonard Calabrese

“COVID-19 deserves a serious place in the pantheon of pandemics,” Leonard Calabrese, DO, RJ Fasenmyer, president of clinical immunology at the Cleveland Clinic, said in his presentation.

Source: Adobe Stock.
“The intersection of viruses and immune-mediated disease is still poorly understood,” Leonard Calabrese, DO, told the participants. Specifically, he noted that the “very heterogeneous” nature of COVID-19 itself has made it an intangible target. Source: Adobe Stock

Calabrese provided a brief overview of the political and social challenges that COVID-19 presents, before ultimately focusing on the role that science has played in combating the pandemic.

He suggested that the nearly 6 million deaths are a “gross underestimation” of the actual effect the virus has had. More worrying has been the popular reaction, especially in political arenas and on social media. “You can see how sadly unprepared we are for this,” he said.

But as he has mentioned in similar conversations over the last 2 years, Calabrese highlighted the work that the scientific community has done with cautious optimism. Specifically for rheumatologists, COVID-19 has focused on immune-mediated diseases like never before. With the light shining, the challenges take shape.

“That the intersection of viruses and immune-mediated disease still poorly understood, ”Calabrese said. Specifically, the “very heterogeneous” nature of COVID-19 itself has made it an intangible 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 strengthening the antiviral defenses,” he said. “In the later stages, we use immunomodulatory therapies, led by dexamethasone.”

Calabrese described the success of dexamethasone in immune-mediated COVID-19 setting as an unexpected turn, as the drug is generally avoided in patients with these conditions. “It’s surprising that dexamethasone has saved this pandemic,” he said.

But more needs to be done to refine treatment methods. “We lack useful biomarkers,” Calabrese said. “So far, artificial intelligence and mechanical learning have generated thousands of papers on this, but nothing we use at bedside.”

It is not only machines that create data. The speed and progress of scientific literature on COVID-19 is good news / bad news suggestions, according to Calabrese. About 250,000 peer-reviewed articles have been published since January 2020, of which 18,000 are 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 understand all this information, but he encouraged the participants to try to digest as much of it as possible. “We have to adapt to this,” he said. “We can not fight it.”

Calabrese highlighted a few important clinical and research challenges for the coming months and years. One is to understand the role of the interferon pathway in some patients experiencing severe COVID-19. Another is the production of anti-COVID-19 autoantibodies in certain individuals over the age of 70. “This is a story in development,” he said.

Another challenge for clinicians is to understand what happens in both the upper and lower respiratory tract as the virus develops. “There are still a lot of ignorant people about this too,” Calabrese said.

Further downstream, Calabrese believes that individuals experience “long COVID” symptoms can become a formidable patient population. “It’s our next big health challenge,” Calabrese said.

“The last question, of course, is: how will this pandemic end?” he said. “No one really knows.”

Although the end is uncertain, the near future is clear, according to Calabrese. “COVID-19 is not going to go away,” he said. “This virus is with us now. It’s part of the structure of humanity.”

Like many experts, Calabrese expressed a reasonable and rational hope that the virulence of the virus will decrease with each variant. “But we do not know,” he said.

In the end, Calabrese gave a sharp portrait of the present moment. “We have two pandemics,” he said. “There is one in healthy and vaccinated. But the other is in immunocompromised and unvaccinated. “

Calabrese recognized that unvaccinated populations are in some ways a separate problem from what rheumatologists face every day when dealing with their patients with immune-mediated diseases. But as for those patients, he was aware of the work to be done. “We have a long way to go.”

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