Cognitive functioning in patients with neuro-PASC: the role of fatigue, mood, and hospitalization status

Patient-reported outcomes (PROs) are essential when evaluating many new treatments in health care; yet, current measures have been limited by a lack of precision, standardization, and comparability of scores across studies and diseases. The Patient-Reported Outcomes Measurement Information System (PROMIS) provides item banks that offer the potential for efficient (minimizes item number without compromising reliability), flexible (enables optional use of interchangeable items), and precise (has minimal error in estimate) measurement of commonly studied PROs. We report results from the first large-scale testing of PROMIS items. Fourteen item pools were tested in the U.S. general population and clinical groups using an online panel and clinic recruitment. A scale-setting subsample was created reflecting demographics proportional to the 2000 U.S. census. Using item-response theory (graded response model), 11 item banks were calibrated on a sample of 21,133, measuring components of self-reported physical, mental, and social health, along with a 10-item Global Health Scale. Short forms from each bank were developed and compared with the overall bank and with other well-validated and widely accepted ("legacy") measures. All item banks demonstrated good reliability across most of the score distributions. Construct validity was supported by moderate to strong correlations with legacy measures. PROMIS item banks and their short forms provide evidence that they are reliable and precise measures of generic symptoms and functional reports comparable to legacy instruments. Further testing will continue to validate and test PROMIS items and banks in diverse clinical populations. Copyright © 2010 Elsevier Inc. All rights reserved.

Background Adverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors. In this electronic health record network cohort study using data from 69 million individuals, 62 354 of whom had a diagnosis of COVID-19, we assessed whether a diagnosis of COVID-19 (compared with other health events) was associated with increased rates of subsequent psychiatric diagnoses, and whether patients with a history of psychiatric illness are at a higher risk of being diagnosed with COVID-19. Methods We used the TriNetX Analytics Network, a global federated network that captures anonymised data from electronic health records in 54 health-care organisations in the USA, totalling 69·8 million patients. TriNetX included 62 354 patients diagnosed with COVID-19 between Jan 20, and Aug 1, 2020. We created cohorts of patients who had been diagnosed with COVID-19 or a range of other health events. We used propensity score matching to control for confounding by risk factors for COVID-19 and for severity of illness. We measured the incidence of and hazard ratios (HRs) for psychiatric disorders, dementia, and insomnia, during the first 14 to 90 days after a diagnosis of COVID-19. Findings In patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events (HR 2·1, 95% CI 1·8–2·5 vs influenza; 1·7, 1·5–1·9 vs other respiratory tract infections; 1·6, 1·4–1·9 vs skin infection; 1·6, 1·3–1·9 vs cholelithiasis; 2·2, 1·9–2·6 vs urolithiasis, and 2·1, 1·9–2·5 vs fracture of a large bone; all p<0·0001). The HR was greatest for anxiety disorders, insomnia, and dementia. We observed similar findings, although with smaller HRs, when relapses and new diagnoses were measured. The incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18·1% (95% CI 17·6–18·6), including 5·8% (5·2–6·4) that were a first diagnosis. The incidence of a first diagnosis of dementia in the 14 to 90 days after COVID-19 diagnosis was 1·6% (95% CI 1·2–2·1) in people older than 65 years. A psychiatric diagnosis in the previous year was associated with a higher incidence of COVID-19 diagnosis (relative risk 1·65, 95% CI 1·59–1·71; p<0·0001). This risk was independent of known physical health risk factors for COVID-19, but we cannot exclude possible residual confounding by socioeconomic factors. Interpretation Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae, and a psychiatric diagnosis might be an independent risk factor for COVID-19. Although preliminary, our findings have implications for clinical services, and prospective cohort studies are warranted. Funding National Institute for Health Research.

There is strong evidence of brain-related abnormalities in COVID-19 1–13 . However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.