Change in Neuropsychological Test Performance Seen in a Longitudinal Study of Patients With Post-acute Sequelae of COVID-19: A 6-Month Follow-up Study.

BACKGROUND: Post-acute sequelae of COVID-19 may include physical, psychiatric, and neurocognitive symptoms. Few studies of cognitive symptoms have been longitudinal, with many following participants briefly after infection and relying on subjective complaints, screening instruments, or computerized testing. This group previously reported diminished neuropsychological (NP) test performance in over half of 60 individuals tested in-person 7 months post-COVID-19, particularly those seeking care for cognitive complaints. The current study describes the initial and 6-month follow-up results of an expanded cohort of 75 participants. OBJECTIVE: To measure longitudinal changes in neuropsychological test performance, as well as medical and psychiatric changes, post-COVID-19. METHODS: Participants underwent NP, psychiatric, and medical assessments approximately 7 months after acute COVID-19 infection. Sixty-three (84%) returned approximately 6 months later for repeat evaluation. RESULTS: At the initial visit, 29 (38.7%) met criteria for low NP performance, and 16 (21.3%) met criteria for extremely low NP performance. At 6-month follow-up, several NP domains that were significantly below normative values at the initial visit were no longer abnormal, with the exception of language. Only measures of delayed memory and fatigue showed significant improvements between the 2 time points. CONCLUSIONS: A substantial proportion of individuals recovered from acute COVID-19 infection have persistent neuropsychiatric symptoms over 1 year after infection. While the overall sample in this study showed some improvement in NP test performance relative to norms, only fatigue and delayed memory improved significantly between times 1 and 2. No individual declined in NP test performance, though relatively few individuals made significant clinical improvement, indicating the need for serial neuropsychiatric assessment and treatment supports. Longitudinal follow-up of this cohort is in progress.

Frequency and Characteristics of Depression and Its Association with Diminished Quality of Life in a Cohort of Individuals with Post-Acute Sequelae of COVID-19.

Background: Approximately one-third of COVID-19 survivors will experience persistent symptoms, which may include neurological and psychiatric disturbances. Previous research has suggested that up to 45% of people develop clinically significant depressive symptoms post-COVID. This study sought to determine frequency, symptom profile, and clinical correlates of depression post-COVID. Methods: Seventy-five participants who had recovered from COVID-19 underwent neurocognitive, psychiatric, medical, and cognitive testing/screening. The primary measures of interest in this report included the Patient Health Questionnaire (PHQ-9), a 9-item depression-screening tool, and the Endicott Quality of Life Enjoyment and Satisfaction Questionnaire. Results: One-third of study participants screened as positive on the PHQ-9 for clinically significant depression, with the most commonly reported symptom being fatigue, followed by sleep disturbance and poor concentration. Also reported were decreased satisfaction in employment, sexual life, and mood. Depressed patients described greater illness severity during COVID-19 infection and subjective cognitive impairment, which was not found on neurocognitive testing. The only significant predictor of depression was COVID-19 illness severity. Limitations: A significant portion of participants was a clinical population with specific post-COVID complaints and was predominately comprised of white females. Formal psychiatric evaluation was not performed. Conclusion: Many individuals may experience depression after COVID-19 infection, with symptoms appearing to be predominately somatic in nature and correspond with COVID-19 illness severity.

Impact of COVID-19 on employment: sociodemographic, medical, psychiatric and neuropsychological correlates.

Introduction: Given the nature of the persistent physical and neuropsychiatric symptoms reported in the literature, among individuals after acute COVID illness; there is growing concern about the functional implications of the Post-Acute Sequelae of COVID-19 (PASC). We aim to evaluate associations of sociodemographic, medical, psychiatric and neuropsychological factors with employment status post COVID-19. Methods: 59 participants were administered a neuropsychiatric assessment and queried about employment status and occupational difficulties months after quarantine. Two levels of comparison were conducted: (1) Those who took time off work (TTO) to those with no time off (NTO); (2) Those who reported occupational performance suffered (PS) to those who did not (PDNS). Results: TTO vs. NTO exhibited extensive differences across medical, psychiatric and neurocognitive domains. PS vs. PDNS differed on subjective measures of physical and cognitive symptoms, but not on objective testing. Conclusion: Individuals who took time off beyond COVID-19 quarantine experience persistent physical, psychiatric, subjective and objective neurocognitive burden. In contrast, occupational impairment appears to reflect subjective complaints, but not objective measures. Clinical implications are discussed.

Anxiety and posttraumatic stress in post-acute sequelae of COVID-19: prevalence, characteristics, comorbidity, and clinical correlates.

Background: Anxiety and post-traumatic stress symptoms have been reported in association with acute and post-acute sequelae of COVID-19 (PASC). Purpose: This study aimed to document the cross-sectional prevalence, characteristics and clinical correlates of anxiety and post-traumatic stress in a study of neuropsychiatric sequelae of COVID-19. Method: 75 participants recruited from a post-COVID-19 recovery program and the community were assessed for sociodemographic, medical, psychiatric, and neurocognitive symptoms and performance. The generalized anxiety questionnaire-7 (GAD-7) and post-traumatic stress disorder questionnaire for DSM5 (PCL5) were utilized to measure anxiety and PTSD symptoms. Established cutoff scoring for the GAD-7 and algorithm-based scoring of the PCL5 were utilized to determine clinically significant anxiety symptoms and PTSD, respectively. Results: The cohort was 71% female, 36% ethnic minority, with the main age of 43.5 years, 80% employment, 40% with the prior psychiatric treatment history and 2/3 seeking post-COVID care for PASC. Clinically significant anxiety symptoms were found in 31% and PTSD was found in 29% of the cohort. Nervousness and excessive worry were the most prominent anxiety symptoms, while changes in mood/cognition and avoidance were most frequent in PTSD. There was a high degree of comorbidity between clinically significant anxiety symptoms, PTSD, depression and fatigue. In logistic regression, acute COVID illness severity, prior psychiatric history, and memory complaints (but not objective neuropsychological performance) predicted clinically significant anxiety symptoms and/or PTSD. Conclusion: Clinically significant anxiety and PTSD are found in approximately 1 of 3 individuals after COVID-19 infection. They are highly comorbid with each other as well as with depression and fatigue. All patients seeking care for PASC should be screened for these neuropsychiatric complications. Symptoms of worry, nervousness, subjective changes in mood, and cognition as well as behavioral avoidance are particularly important targets of clinical intervention.

Frequency, Characteristics, and Correlates of Cognitive Complaints in a Cohort of Individuals with Post-Acute Sequelae of COVID-19.

BACKGROUND: Cognitive complaints are among the most frequent symptoms of post-acute sequelae of COVID-19 (PASC). This study aimed to investigate the frequency, characteristics, and clinical correlates of cognitive complaints (CC) in PASC, particularly in relation to objective neuropsychological (NP) performance. METHODS: Seventy-four participants underwent psychiatric, medical, and NP testing approximately 7 months after acute COVID-19. The Patient Assessment of Own Functioning Inventory (PAOFI) was used to characterize the frequency and severity of CC in domains of memory, language, and cognitive/executive function. The associations of CC with sociodemographic, medical, psychiatric, and NP variables were assessed utilizing correlational analysis, logistic regression, and pairwise comparisons of those categorized as having CC vs. not having CC. RESULTS: Taken together, approximately one-third of the study participants had clinically significant CC. Memory difficulty was the most frequent CC, although all categories were frequently endorsed. Memory and cognitive/executive complaints correlated with NP tests in these and multiple other NP domains. CC were more likely to be under-reported in those with diminished NP performance than over-reported in those without diminished performance. Acute COVID-19 symptom severity, elevated depressive symptoms, and NP tests of diminished attention and psychomotor processing speed were independent predictors of CC in logistic regression. CONCLUSIONS: Cognitive complaints after acute COVID-19 should be taken seriously, as they are likely to reflect diminished NP performance, as well as medical, psychiatric, and functional burdens. However, patients with PASC may not accurately identify or characterize objective cognitive difficulties, so programs offering comprehensive care for patients with PASC should offer formal neuropsychological testing.

Screening for brain fog: Is the montreal cognitive assessment an effective screening tool for neurocognitive complaints post-COVID-19?

BACKGROUND: Cognitive complaints are one of the most frequent symptoms reported in post-acute sequelae of COVID-19 (PASC). The Montreal Cognitive Assessment (MoCA) has been used to estimate prevalence of cognitive impairment in many studies of PASC, and is commonly employed as a screening test in this population, however, its validity has not been established. OBJECTIVE: To determine the utility of the MoCA to screen for cognitive impairment in PASC. METHODS: Sixty participants underwent neuropsychological, psychiatric, and medical assessments, as well as the Montreal Cognitive Assessment, 6-8 months after acute COVID-19 infection. RESULTS: The overall sample had a mean score of 26.1 on the MoCA, with approximately one third screening below the cutoff score of 26, similar to the rate of extremely low NP test performance. MoCA score was inversely correlated with fatigue and depression measures and ethnic minority participants scored on average lower, despite similar education and estimated premorbid function. The MoCA had an accuracy of 63.3% at detecting any degree of diminished NP performance, and an accuracy of 73.3% at detecting extremely low NP performance. DISCUSSION/CONCLUSION: The MoCA may not be accurate for detecting neither mild nor more severe degrees of diminished NP test performance in PASC. Therefore, patients with persistent cognitive complaints in the setting of PASC who score in the normal range on the MoCA should be referred for formal NP assessment.

Neuropsychological, Medical, and Psychiatric Findings After Recovery From Acute COVID-19: A Cross-sectional Study.

BACKGROUND: Persistent cognitive, medical and psychiatric complaints have been extensively described after recovery from acute SARS-CoV-2 infection. OBJECTIVE: To describe neuropsychological, medical, psychiatric, and functional correlates of cognitive complaints experienced after recovery from acute COVID-19 infection. METHODS: Sixty participants underwent neuropsychological, psychiatric, medical, functional, and quality-of-life assessments 6-8 months after acute COVID-19. Those seeking care for cognitive complaints in a post-COVID-19 clinical program for post-acute symptoms of COVID-19 (clinical group, N = 32) were compared with those recruited from the community who were not seeking care (nonclinical, N = 28). A subset of participants underwent serological testing for proinflammatory cytokines C-reactive protein, interleukin-6, and tumor necrosis factor-α to explore correlations with neuropsychological, psychiatric, and medical variables. RESULTS: For the entire sample, 16 (27%) had extremely low test scores (less than second percentile on at least 1 neuropsychological test). The clinical group with cognitive complaints scored lower than age-adjusted population norms in tests of attention, processing speed, memory, and executive function and scored significantly more in the extremely low range than the nonclinical group (38% vs. 14%, P < 0.04). The clinical group also reported higher levels of depression, anxiety, fatigue, posttraumatic stress disorder, and functional difficulties and lower quality of life. In logistic regression analysis, scoring in the extremely low range was predicted by acute COVID-19 symptoms, current depression score, number of medical comorbidities, and subjective cognitive complaints in the areas of memory, language, and executive functions. Interleukin-6 correlated with acute COVID symptoms, number of medical comorbidities, fatigue, and inversely with measures of executive function. C-reactive protein correlated with current COVID symptoms and depression score but inversely with quality of life. CONCLUSION: Results suggest the existence of extremely low neuropsychological test performance experienced by some individuals months after acute COVID-19 infection, affecting multiple neurocognitive domains. This extremely low neuropsychological test performance is associated with worse acute COVID-19 symptoms, depression, medical comorbidities, functional complaints, and subjective cognitive complaints. Exploratory correlations with proinflammatory cytokines support further research into inflammatory mechanisms and viable treatments.

Characteristics of Calls to a COVID-19 Mental Health Hotline in the First Wave of the Pandemic in New York.

This report describes the development, implementation and outcomes of a "COVID-19 Anxiety Hotline," designed to address the community's mental health crisis provoked by the coronavirus pandemic. The service was specifically designed using survey data regarding the effects of the COVID-19 pandemic on its staff and community members. Callers had around-the-clock direct access to mental healthcare providers at no cost. Quantitative analysis showed that nearly three out of four callers experienced new onset anxiety and insomnia driven by fear of exposure, and had difficulty accessing mental health care. In addition to immediate support, referral to tele-mental health care was provided to 86% of callers. Qualitative analysis indicates the effectiveness of immediate support and appropriate referrals using a tele-health platform. Our report indicates that the service was utilized by the general population, by health care workers, and rapidly provided referrals to individuals with limited access to mental health care during the pandemic.

Psychiatric emergencies during the height of the COVID-19 pandemic in the suburban New York City area.

BACKGROUND: This report characterizes patients presenting for psychiatric emergencies during the COVID-19 pandemic and describes COVID-19-related stressors. METHODS: Patients seen for emergency psychiatric evaluation during the height of the COVID-19 period (March 1-April 30, 2020; N = 201) were compared with those in the immediate Pre-COVID-19 period (January 1-February 28, 2020; N = 355), on sociodemographic characteristics, psychiatric diagnoses, symptoms, and disposition. Patients tested positive for COVID-19 were compared with those that tested negative on the same outcomes. Prevalence and nature of COVID-19-stressors that influenced the emergency presentation were rated. OUTCOME: The most common psychiatric diagnoses and presenting symptoms during both periods were depression and suicidal ideation. Comparing the Pre-COVID-19 and COVID-19 periods, a significant decline in emergency psychiatric volume was observed in children and adolescents (C/A), but not adults. COVID-19 period C/A patients had more new onset disorders and were more likely to be admitted to inpatient care, but were less likely to present with suicide attempts, impulse control disorders and agitation/aggression. Adults were more likely to have no access to outpatient care, present with anxiety disorders, and were also more likely to be admitted for inpatient care. COVID-19 directly affected the psychiatric emergency in 25% of patients, with the more severe stressors triggered by fear of COVID infection (including psychosis), actual COVID infection in self or family members, including death of a loved one. COVID-positive patients were more likely to have psychosis, including new-onset, and were less likely to be depressed/suicidal compared to their COVID-negative counterparts. CONCLUSION: This report demonstrates the need for emergency psychiatric services throughout the COVID-19 pandemic and the need for clinical and diagnostic COVID-19 screening of psychiatric emergency patients. New and severe pathology underscore the need for enhanced outpatient access to tele-mental health, crisis hotline and on-line psychotherapeutic services, as well as psychiatric inpatient services with capacity to safely care for COVID-19 patients.

A conserved, N-terminal tyrosine signal directs Ras for inhibition by Rabex-5.

Dysregulation of the Ras oncogene in development causes developmental disorders, "Rasopathies," whereas mutational activation or amplification of Ras in differentiated tissues causes cancer. Rabex-5 (also called RabGEF1) inhibits Ras by promoting Ras mono- and di-ubiquitination. We report here that Rabex-5-mediated Ras ubiquitination requires Ras Tyrosine 4 (Y4), a site of known phosphorylation. Ras substitution mutants insensitive to Y4 phosphorylation did not undergo Rabex-5-mediated ubiquitination in cells and exhibited Ras gain-of-function phenotypes in vivo. Ras Y4 phosphomimic substitution increased Rabex-5-mediated ubiquitination in cells. Y4 phosphomimic substitution in oncogenic Ras blocked the morphological phenotypes associated with oncogenic Ras in vivo dependent on the presence of Rabex-5. We developed polyclonal antibodies raised against an N-terminal Ras peptide phosphorylated at Y4. These anti-phospho-Y4 antibodies showed dramatic recognition of recombinant wild-type Ras and RasG12V proteins when incubated with JAK2 or SRC kinases but not of RasY4F or RasY4F,G12V recombinant proteins suggesting that JAK2 and SRC could promote phosphorylation of Ras proteins at Y4 in vitro. Anti-phospho-Y4 antibodies also showed recognition of RasG12V protein, but not wild-type Ras, when incubated with EGFR. A role for JAK2, SRC, and EGFR (kinases with well-known roles to activate signaling through Ras), to promote Ras Y4 phosphorylation could represent a feedback mechanism to limit Ras activation and thus establish Ras homeostasis. Notably, rare variants of Ras at Y4 have been found in cerebellar glioblastomas. Therefore, our work identifies a physiologically relevant Ras ubiquitination signal and highlights a requirement for Y4 for Ras inhibition by Rabex-5 to maintain Ras pathway homeostasis and to prevent tissue transformation.