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Nearly a quarter of hospitalised COVID-19 patients have ‘brain fog’ — Mount Sinai registry

Nearly a quarter of COVID-19 patients in a Mount Sinai Health System registry experienced some issues with their memory, found a study in JAMA Network Open.

The research, published in the journal JAMA Network Open, found that nearly a quarter of COVID-19 patients in a Mount Sinai Health System registry experienced some issues with their memory, and although hospitalised patients were more likely to have such brain fog after a coronavirus infection, some outpatients had cognitive impairment too.

“We found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalised patients," wrote Jacqueline Becker and her colleagues at the Icahn School of Medicine at Mount Sinai in New York in the study.

They said this pattern was consistent with early reports describing a dysexecutive syndrome after COVID-19. “It has considerable implications for occupational, psychological, and functional outcomes,” they wrote.

Separate research, published in the journal Lancet Psychiatry, found that as many as one in three people with COVID-19 had longer-term mental health or neurological symptoms.

The US Centers for Disease Control and Prevention includes difficulty in thinking or concentrating, sometimes referred to as "brain fog", on its list of post-COVID conditions.

“Although most people with COVID-19 get better within weeks of illness, some people experience post-COVID conditions," the CDC notes on its website. "These conditions are a wide range of new, returning, or ongoing health problems people can experience four or more weeks after first being infected with the virus that causes COVID-19.”

The latest study included data from April 2020 to May 2021, on 740 COVID-19 patients with no history of dementia. The average age of patients was 49. Cognitive functioning was assessed for each patient and the researchers analysed the frequency of cognitive impairment among them.

It was found that 15% showed deficits in phonemic fluency in their speaking; 16% in a set of mental skills called their executive functioning; 18% showed deficits in their cognitive processing speed; 20% in their ability to process categories or lists; 23% in memory recall and 24% in memory encoding, among other impairments.

The researchers noted that hospitalised patients were more likely to have impairments in attention, executive functioning, category fluency and memory. For instance, when it came to memory recall, the researchers found 39% of hospitalised patients had impairment in that area compared with 12% of outpatients. With memory encoding, the data showed that 37% of hospitalised patients had impairment compared with 16% of outpatients.

The authors noted the possibility for bias in the sample because patients came to Mount Sinai Health System because they were experiencing symptoms.

“The association of COVID-19 with executive functioning raises key questions regarding patients’ long-term treatment,” the researchers wrote. “Future studies are needed to identify the risk factors and mechanisms underlying cognitive dysfunction as well as options for rehabilitation.”

Study details (JAMA)

Assessment of Cognitive Function in Patients After COVID-19 Infection

Jacqueline Becker, Jenny Lin, Molly Doernberg, Kimberly Stone, Allison Navis, Joanne Festa, Juan Wisnivesky.

Published in JAMA Network on 22 October 2021

People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association with disease severity are not well characterised. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning.
We investigated rates of cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency department (ED), or inpatient hospital settings.

We analysed data in this cross-sectional study from April 2020 through May 2021 from a cohort of patients with COVID-19 followed up through a Mount Sinai Health System registry. Study participants were 18 years or older, spoke English or Spanish, tested positive for SARS-CoV-2 or had serum antibody positivity, and had no history of dementia. Participant demographic characteristics (eg, age, race, and ethnicity) were collected via self-report. Cognitive functioning was assessed using well-validated neuropsychological measures: Number Span forward (attention) and backward (working memory), Trail Making Test Part A and Part B (processing speed and executive functioning, respectively), phonemic and category fluency (language), and the Hopkins Verbal Learning Test–Revised (memory encoding, recall, and recognition). The Mount Sinai Health System Institutional Review Board approved this study, and informed consent was obtained from study participants. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

We calculated the frequency of impairment on each measure, defined as a z score of less than or equal to 1.5 SDs below measure-specific age-, educational level–, and sex-adjusted norms. Logistic regression assessed the association between cognitive impairment and COVID-19 care site (outpatient, ED, or hospital), adjusting for race and ethnicity, smoking, body mass index, comorbidities, and depression. The threshold for statistical significance was α = .05, and the tests were 2-tailed. Analyses were performed using SAS, version 9.4 (SAS Institute).

The mean (IQR) age of 740 participants was 49 (38-59) years, 63% (n = 464) were women, and the mean (SD) time from COVID-19 diagnosis was 7.6 (2.7) months (Table 1). Participants self-identified as Black (15%), Hispanic (20%), or White (54%) or selected multiracial or other race and ethnicity (11%; other race included Asian [4.5%, n = 33)] and those who selected “other” as race). The most prominent deficits were in processing speed (18%, n = 133), executive functioning (16%, n = 118), phonemic fluency (15%, n = 111) and category fluency (20%, n = 148), memory encoding (24%, n = 178), and memory recall (23%, n = 170; Table 2).

In adjusted analyses, hospitalised patients were more likely to have impairments in attention (odds ratio [OR]: 2.8; 95% CI: 1.3-5.9), executive functioning (OR: 1.8; 95% CI: 1.0-3.4), category fluency (OR: 3.0; 95% CI: 1.7-5.2), memory encoding (OR: 2.3; 95% CI: 1.3-4.1), and memory recall (OR: 2.2; 95% CI: 1.3-3.8) than those in the outpatient group. Patients treated in the ED were more likely to have impaired category fluency (OR: 1.8; 95% CI: 1.1-3.1) and memory encoding (OR: 1.7; 95% CI: 1.0-3.0) than those treated in the outpatient setting. No significant differences in impairments in other domains were observed between groups.

Study details (The Lancet)

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Maxime Taquet, Prof John R Geddes, Prof Masud Husain, Sierra Luciano, Prof Paul J Harrison,

Published in The Lancet


Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the six months following a COVID-19 diagnosis.

For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020.

We estimated the incidence of 14 neurological and psychiatric outcomes in the six months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; Parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism.

Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events.

Our study provides evidence for substantial neurological and psychiatric morbidity in the six months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings.


JAMA article – Assessment of Cognitive Function in Patients After COVID-19 Infection (Open access)


The Lancet article – 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records (Open access)


See more from MedicalBrief archives:


Neurological injury biomarkers in acute COVID-19 normalise in the long term – Swedish study


SARS-CoV-2: No brain infection but can inflict significant damage — 40 autopsies


Fauci announces new name for 'COVID long-haulers' and a new study



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