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February 28, 2022
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Much about post-acute COVID syndromes remains ‘poorly defined’

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Despite a growing body of evidence documenting the existence of post-acute COVID-19 syndromes, there remain many more questions than answers, according to data presented at the Basic and Clinical Immunology for the Busy Clinician symposium.

Leonard Calabrese, DO
Leonard Calabrese

Leonard Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, covered long COVID — also called “long-haulers” or post-acute sequelae of COVID-19 (PASC) — from “30,000 feet” in his presentation. The talk covered epidemiology, major endotypes, pathogenesis and emerging therapies.

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“We have to confront ourselves with the challenges of lacking a uniform definition, no specific criteria, serious reporting bias and no diagnostic biomarkers,” Leonard Calabrese, DO, told attendees.

Data on this topic are growing. “The RECOVER study is the first database,” he said. “This will be a fabulous resource but it will be years until we see the full potential of this study.”

That said, early findings have shown evidence running contrary to the assumption that only severe acute infection would lead to sequalae. “Many patients were not symptomatic or pauci-symptomatic,” Calabrese said.

Another issue for consideration is the length of time since infection that qualifies as long COVID. “It is not universally agreed upon,” Calabrese said.

He noted that persistent symptoms a month after infection are “not surprising” and 2 months out are “disturbing.” By 3 months, the symptoms may be ongoing acute infection or they may be moving into the long-term syndrome category. “We are now starting to look at data for 6 months out.”

Regarding manifestations of PASC, Calabrese noted that some 50 symptoms have been logged. “First and foremost is fatigue,” he said. “The rheumatologists who are listening will understand fatigue, even if patients have a difficult time articulating it.”

Pain, cough, tachycardia and brain fog are other major issues, along with appetite loss. “There is incontrovertible evidence that some tachycardia occurs post-COVID,” Calabrese said.

As for brain fog, even patients who had very mild disease could experience this outcome, according to Calabrese. But it does not end there.

“There is also some data suggesting neurocognitive defects that could be correlated with surrogate IQ effects,” he said. Patients who had severe COVID, particularly those aged 50 to 70 years, have experienced losses in IQ score of up to seven points. “When people talk about brain fog, they are not just talking about forgetting their grocery list. We need to robustly evaluate this.”

Epidemiology of long hauler syndrome is variable. Across countries, PASC rates range from 10%-80%. “In the U.S.A., one in three patients will have symptoms at 3 months,” Calabrese said. “Globally, it is about one in four.”

Calabrese challenged attendees to consider some epidemiological questions. “We have to confront ourselves with the challenges of lacking a uniform definition, no specific criteria, serious reporting bias and no diagnostic biomarkers,” he said.

Regarding risk factors, Calabrese noted, unsurprisingly, that older patients may be more likely to develop long COVID, along with women and patients with some frailty.

Unfortunately, there are “no specific therapies” for long COVID at the current moment, Calabrese said. With this in mind, he urged attendees to consider the humanity of the medical profession. “There is stress on both the patient and provider” in dealing with these “poorly defined” manifestations. “We need to give them our time, our ear and our voice. Simply talking to them is empathic.”