Procedural Motor Memory Deficits in Patients With Long-COVID.

BACKGROUND AND OBJECTIVES: At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms ("Long-COVID") including "brain fog" and deficits in declarative memory. It is not known if Long-COVID affects patients' ability to form and retain procedural motor skill memories. The objective was to determine the ability of patients with Long-COVID to acquire and consolidate a new procedural motor skill over 2 training days. The primary outcome was to determine difference in early learning, measured as the increase in correct sequence typing speed over the initial 11 practice trials of a new skill. The secondary outcomes were initial and final typing speed on days 1 and 2, learning rate, overnight consolidation, and typing accuracy. METHODS: In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days (NCT05746624). Patients with Long-COVID (reporting persistent post-coronavirus disease 2019 [COVID-19] symptoms for more than 4 weeks) were recruited at the NIH. Patients were matched one-to-one by age and sex to controls recruited during the pandemic using a crowd-sourcing platform. Selection criteria included age 18-90 years, English speaking, right-handed, able to type with the left hand, denied active fever or respiratory infection, and no previous task exposure. Data were also compared with an age-matched and sex-matched control group who performed the task online before the COVID-19 pandemic (prepandemic controls). RESULTS: In total, 105 of 236 patients contacted agreed to participate and completed the experiment (mean ± SD age 46 ± 12.8 years, 82% female). Both healthy control groups had 105 participants (mean age 46 ± 13.1 and 46 ± 11.9 years, 82% female). Early learning was comparable across groups (Long-COVID: 0.36 ± 0.24 correct sequences/second, pandemic controls: 0.36 ± 0.53 prepandemic controls: 0.38 ± 0.57, patients vs pandemic controls [CI -0.068 to 0.067], vs prepandemic controls [CI -0.084 to 0.052], and between controls [CI -0.083 to 0.053], p = 0.82). Initial and final typing speeds on days 1 and 2 were slower in patients than controls. Patients with Long-COVID showed a significantly reduced overnight consolidation and a nonsignificant trend to reduced learning rates. DISCUSSION: Early learning was comparable in patients with Long-COVID and controls. Anomalous initial performance is consistent with executive dysfunction. Reduction in overnight consolidation may relate to deficits in procedural memory formation.

A clinical primer for the expected and potential post-COVID-19 syndromes.

In late 2019, a novel coronavirus SARS-CoV-2 (COVID-19) spread unchecked across the world's population. With tens of millions infected, the long-term consequences of COVID-19 infection will be a major health care focus for years after the contagion subsides. Most complications stem from direct viral invasion provoking an over-exuberant inflammatory response driven by innate immune cells and activation of the clotting cascade causing thrombosis. Injury to individual organs and their protective linings are frequent presentations in respiratory, cardiovascular, and neurological systems. Reviewing the historical context of postviral fatiguing symptoms seems relevant to understanding reports of uneven recoveries and persistent symptoms that are emerging as "long-haul COVID-19." The pandemic is also an unprecedented sociocultural event, transforming how people consider their health, gather in groups, and navigate their daily lives. The unprecedented sociocultural stresses of the pandemic will have an invisible, ubiquitous, and predictable impact on neurologic, endocrine, and immune functioning, even in people untouched by the virus. COVID-19 may also have a surprise or two in store, with unique clinical presentations and novel mechanisms of injury which are yet to clearly emerge. Although challenging and unfortunate, these times also represent a unique opportunity to start to unravel the physiology that underlie how viruses may trigger cancers, neurological disease, and postviral fatiguing syndromes.