'The wild, wild west': COVID-19 care improves amid hunt for more effective therapies
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Clinicians have an increasing number of options to treat patients with all stages of COVID-19 infection, from pauci-symptomatic early infection to those with long hauler syndromes, noted a speaker at the 2021 Rheumatology Nurses Society annual conference.
Leonard Calabrese, DO, RJ Fasenmyer Chair of the Center for Clinical Immunology at Cleveland Clinic, broke the COVID-19 disease course into three acts. Act one is the innate immune reaction, which is marked by viral engagement of pathogen-associated molecular patterns and production of type 1 interferon. “Interferon is very important to antiviral defense,” Calabrese said. “It is produced in the cell and exported outside the cell to defend other cells.”
The second act is the adaptive immune response, which includes the production of antibodies, T cell response and release of damage-associated molecular patterns. “Adaptive immunity is a more recent addition to the biology of the immune response,” Calabrese said. “It is a characteristic of vertebrates and other long-lived species.”
Most patients are either asymptomatic or pauci-symptomatic through these first two acts, and the virus resolves without much complication, according to Calabrese. However, some patients progress to the third act, which involves the cytokine storm or “cytokine mediated syndrome,” which is marked by production of IL-6, IL-1, TNF, granulocyte-macrophage colony-stimulating factor (GMCSF) and interferon.
In terms of basic treatment paradigms, for patients in the first act who have low symptoms, antiviral medications may be effective, although the research community is still trying to find the most effective agent. “But they are on their way, I expect by the end of the year,” Calabrese said.
Patients who progress require another type of intervention, according to Calabrese. “For the second act, we would like to bolster their interferon very early,” he said.
For the treatment of patients who progress to the third act of COVID-19 infection, Calabrese noted that many drugs in the rheumatology armamentarium have shown efficacy. “We see our drugs, like dexamethasone, IL-6, janus kinase inhibitors, which was just given emergency use authorization 2 weeks ago,” he said. “All things to tone down the immune system.”
That said, Calabrese described the search for a magic bullet drug for act three as “the wild wild West.”
But he stressed that that should not deter rheumatologists from using their knowledge to clinical benefit. “Probably the most important thing for a rheumatology practitioner to know is that several monoclonal antibody treatments, which our patients are eligible for, in patients with mild disease, can dramatically decrease the likelihood of being hospitalized or dying,” he said.
Ever-growing understanding of these treatment paradigms at the three stages of COVID-19 infection has made Calabrese cautiously optimistic. “It is totally clear that we have gotten better at taking care of this disease,” he said. “Mortality in the ICU has now been cut in half. But we think we can do better.”
If there is a final component to the discussion, it pertains to the ever-growing number of patients who are reporting symptoms of so-called “long COVID” after their infection has resolved. “This still lacks a consensus definition,” Calabrese said.
As with investigation into drugs to manage other stages of COVID infection, Calabrese said that the research community is working on understanding these prolonged syndromes. “We are thinking about this in a much more sophisticated way,” he said. “But it is very difficult to study.”
Until the parameters are defined and evidence-based treatments emerge, Calabrese had a simple message for rheumatologists managing patients with this spectrum of long-hauler syndromes. “We have to listen with humility and assume that it is real and not their fault,” he said.
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Calabrese L. Applied Immunology to Autoimmune Diseases: COVID-19 as Immunology Boot Camp (Part 2). Presented at: Rheumatology Nurses Society annual conference; August 4-7, 2021 (virtual meeting).
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