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The only pattern in so-called "long COVID" is there is no pattern, as it appears to affect even those who experienced more mild disease, specialists told clinicians on a CDC call on Thursday.

"Long COVID" is nebulous, particularly because it can overlap with other complications of COVID-19 illness, such as hospitalization complications and post-intensive care syndrome, or even multisystem inflammatory disorder, said Alfonso Hernandez-Romieu, MD, of the CDC.

And there is no standardized definition of the condition, either. Persistent severe fatigue, headache, "brain fog," and mild cognitive impairment are some of the most commonly presenting symptoms, and patients tend to present more than 4 weeks after illness. However, Hernandez-Romieu noted that these symptoms can be independent of disease severity, and can be newly occurring or recurring symptoms.

For example, Hernandez-Romieu said that research out of China showed that three-quarters of patients hospitalized with COVID-19 said they had at least one "ongoing" symptom, and one in five patients not requiring supplemental oxygen during hospitalization reported decreased lung function after 6 months.

While long COVID symptoms span a variety of specialties, respiratory and neurological complaints are among the most common. Jennifer Possick, MD, of Yale University School of Medicine in New Haven, Connecticut, discussed her experience with long COVID in a pulmonary specialty clinic. In her experience, dyspnea, fatigue, and exertional intolerance were most commonly reported, with patients reporting multiple symptoms simultaneously, and a quarter of patients reporting dyspnea 6 months post-infection.

While Possick noted that persistent imaging abnormalities were more common in patients with more severe disease, "impairment in pulmonary function tests, diffusion capacity, and the 6-minute walk test were observed for patients who did not have hypoxemia as part of acute illness, as well," she said.

Since the field of long COVID is relatively new, clinicians only have prior experience from SARS and MERS, as well as with patients with all-cause acute respiratory distress syndrome, from which a minority of patients developed persistent individual changes.

"Although prior experience with SARS ... potentially suggests pulmonary fibrosis is restricted to a minority of patients, this is not yet known with COVID-19," Possick said.

She described the "dominant pattern" of post-COVID pulmonary disease as patients with persistent symptoms with normal pulmonary function tests and thoracic imaging.

She shared her initial clinical model, which included imaging, pulmonary function tests, and 6-minute walk tests, and repeating selected labs to the initial diagnostics when a patient presented with symptoms. Though she noted patients with normal pulmonary function tests did not need repeat imaging, tests were generally repeated at 3, 6, and 12 months, as needed, for severity, along with extrapulmonary consultation.

And even if these symptoms resolve, Possick said patients still may be expected to "demonstrate impairments in physical, cognitive, or psychological functions."

"We did not anticipate how common neuro-cognitive symptoms would be," which evolved into an independent need for a post-COVID neurology program, she said.

Allison Navis, MD, of Icahn School of Medicine at Mount Sinai in New York City, described her experiences with this type of program at her hospital. She also said most patients she was seeing had what would be considered "mild COVID," with a broad range of symptoms, most of which would not be considered pure neurological syndromes with objective deficits.

"Brain fog," she said, was the most common neurological symptom, which she described as a combination of issues with short-term memory, concentration, and word-finding or speech difficulty. There was no correlation with the severity of COVID, and the impact on patients varied, with symptoms fluctuating ("good and bad days").

Other neurological symptoms that patients reported included headaches, which also followed no clear pattern of either migraines or tension headaches, as well as paresthesias, such as tingling or numbness, and dysautonomia, including light-headedness, palpitations, and gastrointestinal disturbances.

Initially, a broad workup was undertaken, including bloodwork, neuroimaging, and neuropsychological testing, she said. But after some experience, Navis said it's likely sufficient to do a small, focused workup, as "extensive testing has not been helpful in the vast majority of patients."

Their current approach involves taking a patient history, including symptoms, severity of COVID, age and medical comorbidities, focal neurological deficits or symptoms, and the impact of symptoms on ability to work or function. Imaging can be considered if the patient had moderate to severe COVID, was age 50 or older, or had medical comorbidities and any focal neurological deficits or symptoms.

Navis said treatment is mostly symptomatic and supportive, since there are no medications to "cure" neurological damage.

Hernandez-Romieu said the CDC is currently involved in a multi-pronged approach to understand and characterize long COVID, including cohort studies, chart reviews, and clinician engagement. However, he noted another limitation to long COVID research: few studies include baseline pre-COVID health status.

"It's important for providers to provide baseline and serial reviews and physical exams," Hernandez-Romieu said. "There's still a lot we do not understand."

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