Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons.

Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by re-expression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral re-expression of ISL1 and LHX3 reactivates aspects of the youthful gene expression program in mature motor neurons and alleviates key disease-relevant phenotypes in the SOD1G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.

Mainz II urinary diversion in low-resource settings: patient outcomes in women with irreparable fistula in Malawi.

BACKGROUND: Obstructed labor leading to a vesicovaginal fistula remains a devastating outcome of childbirth in low-resource countries. Women with an irreparable vesicovaginal fistula may be candidates for a urinary diversion, such as the Mainz II modified ureterosigmoidostomy procedure. Previous reviews state that the procedure should be considered in low-resource countries. However, given the limited duration of postoperative follow-up, these studies do not adequately represent the long-term morbidity and mortality that is likely associated with this procedure. We present data that strongly support avoiding the procedure in low-resource countries. OBJECTIVE: This study aimed to evaluate the postoperative status of the patient (dead, alive, lost to follow-up) and time to death following the Mainz II procedure. STUDY DESIGN: This is a case series including 21 patients who underwent a Mainz II urinary diversion from April 2013 to June 2015 for management of irreparable vesicovaginal fistula at the Fistula Care Centre in Lilongwe, Malawi. Patients were seen postoperatively at 3, 6, 9, and 12 months, followed by every 6 to 12 months thereafter. Descriptive statistics were performed to summarize the data. RESULTS: During the postoperative period, 8 (38.1%; 8/21) patients died, 5 (23.8%; 5/21) were lost to follow-up, and 8 (38.1%; 8/21) are currently alive and followed up at the Fistula Care Centre. We strongly suspect that 7 of the 8 deaths were related to the procedure given that the patients had illnesses that exacerbated the metabolic consequences of the procedure. The eighth patient died after being attacked by robbers. Unfortunately, the exact cause of death could not be determined for these patients. Given that most of the suspected illnesses would be treatable in an otherwise healthy patient, even in this low-resource setting, we surmised that the metabolic compromise from the Mainz II procedure likely contributed to their untimely death. The average time from procedure to death was 58 months, with the earliest death at 10 months and the most recent at 7 years after the procedure. CONCLUSION: The Mainz II procedure is an option for patients with irreparable fistula. However, it should likely not be performed in low-resource countries given the long-term complications that often cannot be adequately addressed in these settings, leading to significant morbidity and mortality.

Clandestine abortion resulting in uterine perforation and a retained foreign body led to generalized peritonitis: a case report from Lilongwe, Malawi.

Abortion is criminalized in Malawi in the absence of a life-threatening condition. Consequently, women often undergo unsafe abortions. A large proportion of abortions performed in Malawi require subsequent treatment at a healthcare facility. We describe the case of a 17-year-old who presented with generalized peritonitis and was found intraoperatively to have a necrotic and perforated uterus with a stick retained in her abdominopelvic cavity from a clandestine abortion. This case demonstrates the need for awareness and vigilance among healthcare providers in all specialties to suspect surgical abortion complications as a cause of generalized peritonitis and points to the need for further studies on the optimal management of such patients.

Use of Electronic Health Record-Based Measures to Assess Quality of Care for Pediatric Agitation.

OBJECTIVES: Acute agitation during pediatric mental health emergency department (ED) visits presents safety risks to patients and staff. We previously convened multidisciplinary stakeholders who prioritized 20 proposed quality measures for pediatric acute agitation management. Our objectives were to assess feasibility of evaluating performance on these quality measures using electronic health record (EHR) data and to examine performance variation across 3 EDs. METHODS: At a children's hospital and 2 nonchildren's hospitals, we assessed feasibility of evaluating quality measures for pediatric acute agitation management using structured EHR data elements. We retrospectively evaluated measure performance during ED visits by children 5 to 17 years old who presented for a mental health condition, received medication for agitation, or received physical restraints from July 2020 to June 2021. Bivariate and multivariable regression were used to examine measure performance by patient characteristics and hospital. RESULTS: We identified 2785 mental health ED visits, 275 visits with medication given for agitation, and 35 visits with physical restraints. Performance was feasible to measure using EHR data for 10 measures. Nine measures varied by patient characteristics, including 4.87 times higher adjusted odds (95% confidence interval 1.28-18.54) of physical restraint use among children with versus without autism spectrum disorder. Four measures varied by hospital, with physical restraint use varying from 0.5% to 3.3% of mental health ED visits across hospitals. CONCLUSIONS: Quality of care for pediatric acute agitation management was feasible to evaluate using EHR-derived quality measures. Variation in performance across patient characteristics and hospitals highlights opportunities to improve care quality.

A comparison study: The use of digital and conventional impression techniques in dental hygiene education.

PURPOSE/OBJECTIVES: The study aimed to assess the applicability of digital intraoral scanning in dental hygiene education and compare the quality, efficiency, and ease of use to conventional impression techniques. METHODS: Twenty-eight first-year dental hygiene students (DH1) at UTHealth Houston School of Dentistry (UTSD) participated in this 2022 study. Each student participated in two 4-h lab sessions. Students took traditional alginate impressions and digital intraoral scans using Planmeca Romexis on standardized teeth during the first and second sessions. Both techniques were assessed by faculty for quality and efficiency using a standardized rubric. Participants completed a post-survey providing insight into their perceptions of both techniques and ease of use. RESULTS: The study had 100% participation in the lab sessions and survey responses (N = 28). The results showed digital scanning produced a statistically higher quality product than conventional alginate impressions (p = 0.023). The study found no statistical difference in the efficiency between the two methods. The majority of students (82%) agreed that digital intraoral scanning was easy to use (p = 0.001), and 89% agreed they would use digital intraoral scanning in clinical courses to help with patient care (p = 0.03). CONCLUSION: In this study, dental hygiene students with limited clinical experience learned new technology and used it to produce quality impressions compared to the conventional technique, indicating the value of introducing digital dentistry early in dental hygiene education.

Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by cell-type-specific tau lesions in neurons and glia. Prior work uncovered transcriptome changes in human PSP brains, although their cell-specificity is unknown. Further, systematic data integration and experimental validation platforms to prioritize brain transcriptional perturbations as therapeutic targets in PSP are currently lacking. In this study, we combine bulk tissue (n = 408) and single nucleus RNAseq (n = 34) data from PSP and control brains with transcriptome data from a mouse tauopathy and experimental validations in Drosophila tau models for systematic discovery of high-confidence expression changes in PSP with therapeutic potential. We discover, replicate, and annotate thousands of differentially expressed genes in PSP, many of which reside in glia-enriched co-expression modules and cells. We prioritize DDR2, STOM, and KANK2 as promising therapeutic targets in PSP with striking cross-species validations. We share our findings and data via our interactive application tool PSP RNAseq Atlas ( https://rtools.mayo.edu/PSP_RNAseq_Atlas/ ). Our findings reveal robust glial transcriptome changes in PSP, provide a cross-species systems biology approach, and a tool for therapeutic target discoveries in PSP with potential application in other neurodegenerative diseases.

Urinary tract reconstruction for iatrogenic fistula secondary to radical hysterectomy: Cases from Malawi's Fistula Care Center.

Complications from radical hysterectomy in low-income countries (LICs) are largely unreported in the medical literature. We report on three cases of urinary tract reconstruction performed at the Fistula Care Center (FCC) in Lilongwe, Malawi for iatrogenic fistula following radical hysterectomy. These cases demonstrate the diversity and complexity of reconstruction techniques required and emphasize the need for careful tracking of surgical outcomes of radical hysterectomy.

Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

Voice Acoustics and Vocal Effort in Mask-Wearing Healthcare Professionals: A Comparison Pre- and Post-Workday.

OBJECTIVE: We evaluated voice acoustics and self-perceptual ratings in healthcare workers required to wear face masks throughout their workday. METHODS: Eighteen subjects (11 cisgender female, 7 cisgender male; M = 33.72 years, SD = 8.30) completed self-perceptual ratings and acoustic recordings before and after a typical workday. Chosen measures were specific to vocal effort, dysphonia, and laryngeal tension. Mixed effects models were calculated to determine the impact of session, mask type, sex, and their interactions on the set of perceptual and acoustic measures. RESULTS: The subjects self-reported a significant increase in vocal effort following the workday. These perceptual changes coincided with an increase in vocal intensity and harmonics-to-noise ratio, but decrease in relative fundamental frequency offset 10. As expected, men and women differed in measures related to fundamental frequency and vocal tract length. CONCLUSION: Healthcare professionals wearing masks reported greater vocal symptoms post-workday compared to pre-workday. These symptoms coincided with acoustic changes previously related to vocal effort; however, the degree of change was considered mild. Further research is needed to determine whether vocal hygiene strategies may reduce vocal symptoms in mask-wearing workers.

Development and preliminary validation of the challenges of living with cystic fibrosis (CLCF) questionnaire: a 46-item measure of treatment burden for parent/carers of children with CF.

OBJECTIVE: Treatments for cystic fibrosis (CF) are complex, labour-intensive, and perceived as highly burdensome by caregivers of children with CF. An instrument assessing burden of care is needed. DESIGN: A stepwise, qualitative design was used to create the CLCF with caregiver focus groups, participant researchers, a multidisciplinary professional panel, and cognitive interviews. MAIN OUTCOME MEASURES: Preliminary psychometric analyses evaluated the reliability and convergent validity of the CLCF scores. Cronbach's alpha assessed internal consistency and t-tests examined test-retest reliability. Correlations measured convergence between the Treatment Burden scale of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the CLCF. Discriminant validity was assessed by comparing CLCF scores in one vs two-parent families, across ages, and in children with vs without Pseudomonas aeruginosa (PA). RESULTS: Six Challenge subscales emerged from the qualitative data and the professional panel constructed a scoresheet estimating the Time and Effort required for treatments. Internal consistency and test-retest reliability were adequate. Good convergence was found between the Total Challenge score and Treatment Burden on the CFQ-R (r=-0.49, p = 0.02, n = 31). A recent PA infection signalled higher Total Challenge for caregivers (F(23)11.72, p = 0.002). CONCLUSIONS: The CLCF, developed in partnership with parents/caregivers and CF professionals, is a timely, disease-specific burden measure for clinical research.

Fifteen-minute consultation: An overview of major incidents.

Major incidents are rare but require a large amount of preparation, co-ordination and communication across different emergency services and specialities. This ensures that casualties are efficiently managed within the constraints of limited clinical resources. This article aims to provide a brief understanding of what constitutes as a major incident, how it is declared and the chain of command in communication and action, focusing specifically on the paediatric process. It also aims to highlight important considerations that could potentially be missed (eg, the mental health impact, forensic evidence and so on).

Factors Related to Treatment Attendance for Patients Seeking Gender-Affirming Voice Therapy.

OBJECTIVE: The purpose of this study was to investigate factors related to treatment attendance for patients seeking gender-affirming voice therapy (GAVT). METHOD: We completed retrospective chart reviews of 50 patients (43 transgender women, three transgender men, four nonbinary patients; aged 18-67 years, M = 34.92 years, SD = 12.32 years) referred for GAVT at a Midwest outpatient center from 2016 to 2021. Data extraction included patient demographics, therapy visit specifics (e.g., number of sessions attended, treatment completion status, and in-person vs. virtual visits) and treatment timing (in relation to the onset of the COVID-19 pandemic), and psychosocial and socioeconomic information. RESULTS: There was no impact of treatment-timing relative to the onset of the pandemic on any attendance measure; however, patients were 1.9 times more likely to complete therapy with each virtual telehealth session attended. Individual factors of outside social support and hormone replacement therapy were positively related to the number of therapy sessions attended, whereas insurance provider and employment status were related to therapy completion. CONCLUSIONS: Telehealth attendance during the COVID-19 pandemic was positively associated with GAVT completion. Future research should investigate psychosocial and socioeconomic factors to understand how to identify patients at risk for poor treatment adherence and facilitate access to clinical care.

Current Trends in Immuno-Oncology.

Surgery, radiation, chemotherapy, and targeted therapy were the four basic kinds of cancer treatment until recently. Immuno-oncology (IO), or the concept that cancer cells were damaged by activating the body's immune system, has emerged and is explained as a unique and crucial method for treating different cancers over the last decade. The US Food and Drug Administration and the European Medicines Agency both approved this newly recognized way of treating cancer in 2020. Within IO, different therapeutic classes have arisen, which are the subject of this article. Immune checkpoint inhibitors are currently the most well-known therapeutic class of immuno-oncology medications due to their amazing ability to show efficacy in a variety of tumor types. Biomarkers were tested for different tumors like gastrointestinal cancer, whole Head, lower and upper part Neck cancer, and also cervical cancer by programmed death-ligand 1 (PD-L1) check point and their targets and are currently being utilized prior to treatment by using Pembrolizumab. However, the significance of PD-L1 expression for immune check point reticence therapy in other/different onco-cancer types remains unclear. Homogenized immuneoncology drugs with regular therapy have been recently studied and clinical efficacy outcomes have shown to be significantly improved. While IO agents are fast transforming the marketed treatment for cancer patients, there are still a number of obstacles to overcome in terms of associating their adverse effects and confirming those different healthcare systems, such as financing these expensive therapies. In addition to cancer vaccines and chimeric antigen receptor T-cell treatments, other IO drugs are in pipeline containing chimeric antigen receptor T-cell therapies; earlier ones have their own set of toxicities and high cost related challenges.

Influence of the COVID-19 pandemic on learning preferences and perspectives of generation Y and Z students in dental education.

OBJECTIVES: For the first time in history, the COVID-19 pandemic required students at The University of Texas School of Dentistry (UTSD) to move to remote education. Based on a literature review, it was assumed that younger generations of students would prefer virtual teaching models over in-classroom formats. The purpose of this study is to assess students' perspectives of remote learning during COVID-19 in dental education relative to their generation and programme. METHODS: An electronic survey was administered to all UTSD dental and dental hygiene students via Qualtrics. The survey collected information on demographics, pre-pandemic learning preferences, remote learning experiences during the pandemic, and a free response section. Descriptive statistics and Fisher's exact test were used to analyse data. RESULTS: The survey received a 60% response rate (n = 290). Over 95% of respondents belonged to Generations Y and Z. There were no significant differences in responses between generations. However, significant differences in responses between programmes arose with more dental hygiene students agreed that they liked learning in a classroom setting compared to dental students (p < 0.01). Significantly more dental students agreed that they stayed organized, were less stressed, and felt that the transition to online learning was easy compared to dental hygiene students (p < 0.01). CONCLUSION: Although the majority of students surveyed belong to Generations Y and Z, there are still preferences for traditional, in-person learning. Both cohorts recognized the benefits and challenges of distance learning, and the findings from this study shed light on how students are handling remote learning in dental education.

Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro.

Neurons born in the embryo can undergo a protracted period of maturation lasting well into postnatal life. How gene expression changes are regulated during maturation and whether they can be recapitulated in cultured neurons remains poorly understood. Here, we show that mouse motor neurons exhibit pervasive changes in gene expression and accessibility of associated regulatory regions from embryonic till juvenile age. While motifs of selector transcription factors, ISL1 and LHX3, are enriched in nascent regulatory regions, motifs of NFI factors, activity-dependent factors, and hormone receptors become more prominent in maturation-dependent enhancers. Notably, stem cell-derived motor neurons recapitulate ~40% of the maturation expression program in vitro, with neural activity playing only a modest role as a late-stage modulator. Thus, the genetic maturation program consists of a core hardwired subprogram that is correctly executed in vitro and an extrinsically-controlled subprogram that is dependent on the in vivo context of the maturing organism.

17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson's disease are associated with LRRC37A/2 expression in astrocytes.

BACKGROUND: Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified. METHODS: To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain tissue. RESULTS: We identified three novel H1 sub-haplotype blocks across the 17q21.31 locus associated with PD risk. Protective sub-haplotypes were associated with increased LRRC37A/2 copy number and expression in human brain tissue. We found that LRRC37A/2 is a membrane-associated protein that plays a role in cellular migration, chemotaxis and astroglial inflammation. In human substantia nigra, LRRC37A/2 was primarily expressed in astrocytes, interacted directly with soluble α-synuclein, and co-localized with Lewy bodies in PD brain tissue. CONCLUSION: These data indicate that a novel candidate gene, LRRC37A/2, contributes to the association between the 17q21.31 locus and PD via its interaction with α-synuclein and its effects on astrocytic function and inflammatory response. These data are the first to associate the genetic association at the 17q21.31 locus with PD pathology, and highlight the importance of variation at the 17q21.31 locus in the regulation of multiple genes other than MAPT and KANSL1, as well as its relevance to non-neuronal cell types.

Ranking reprogramming factors for cell differentiation.

Transcription factor over-expression is a proven method for reprogramming cells to a desired cell type for regenerative medicine and therapeutic discovery. However, a general method for the identification of reprogramming factors to create an arbitrary cell type is an open problem. Here we examine the success rate of methods and data for differentiation by testing the ability of nine computational methods (CellNet, GarNet, EBseq, AME, DREME, HOMER, KMAC, diffTF and DeepAccess) to discover and rank candidate factors for eight target cell types with known reprogramming solutions. We compare methods that use gene expression, biological networks and chromatin accessibility data, and comprehensively test parameter and preprocessing of input data to optimize performance. We find the best factor identification methods can identify an average of 50-60% of reprogramming factors within the top ten candidates, and methods that use chromatin accessibility perform the best. Among the chromatin accessibility methods, complex methods DeepAccess and diffTF have higher correlation with the ranked significance of transcription factor candidates within reprogramming protocols for differentiation. We provide evidence that AME and diffTF are optimal methods for transcription factor recovery that will allow for systematic prioritization of transcription factor candidates to aid in the design of new reprogramming protocols.

Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients.

BACKGROUND: Persistent viral RNA shedding of SARS-CoV-2 following COVID-19 has increasingly been recognized, with limited understanding of its implications on outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively assessed for persistent viral shedding across Northwestern Medicine Healthcare (NMHC) patients between March and August 2020. We assessed for predictors of persistent viral shedding, in-hospital delirium, and six-month mortality using binary logistic regression. RESULTS: Of the 2,518 hospitalized patients with an RT-PCR-confirmed diagnosis of COVID-19, 959 underwent repeat SARS-CoV-2 RT-PCR at least fourteen days from initial positive testing. Of those, 405 (42.2%) patients were found to have persistent viral shedding. Persistent viral shedding was associated with male sex, increased BMI, diabetes mellitus, chronic kidney disease, and exposure to corticosteroids during initial COVID-19 hospitalization. Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjusting for factors including severity of respiratory dysfunction (OR 2.45; 95% CI 1.75, 3.45). Even after adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding remained significantly associated with increased six-month mortality (OR 2.43; 95% CI 1.42, 4.29). CONCLUSIONS: Persistent viral shedding occurs frequently in hospitalized COVID-19 patients and is associated with in-hospital delirium and increased six-month mortality.

Evolution of neurologic symptoms in non-hospitalized COVID-19 "long haulers".

OBJECTIVE: We characterized the evolution of neurologic symptoms and self-perceived recovery of non-hospitalized COVID-19 "long haulers" 6-9 months after their initial Neuro-COVID-19 clinic evaluation. METHODS: In this follow-up study on the first 100 patients, 50 SARS-CoV-2 laboratory-positive (SARS-CoV-2+ ), and 50 laboratory-negative (SARS-CoV-2- ), evaluated at our Neuro-COVID-19 clinic between May and November 2020, patients completed phone questionnaires on their neurologic symptoms, subjective impression of recovery and quality of life. RESULTS: Of 52 patients who completed the study (27 SARS-CoV-2+ , 25 SARS-CoV-2- ) a median 14.8 (range 11-18) months after symptom onset, mean age was 42.8 years, 73% were female, and 77% were vaccinated for SARS-CoV-2. Overall, there was no significant change in the frequency of most neurologic symptoms between first and follow-up evaluations, including "brain fog" (81 vs. 71%), numbness/tingling (69 vs. 65%), headache (67 vs. 54%), dizziness (50 vs. 54%), blurred vision (34 vs. 44%), tinnitus (33 vs. 42%), and fatigue (87 vs. 81%). However, dysgeusia and anosmia decreased overall (63 vs. 27%, 58 vs. 21%, both p < 0.001). Conversely, heart rate and blood pressure variation (35 vs. 56%, p = 0.01) and gastrointestinal symptoms (27 vs. 48%, p = 0.04) increased at follow-up. Patients reported improvements in their recovery, cognitive function, and fatigue, but quality of life measures remained lower than the US normative population (p < 0.001). SARS-CoV-2 vaccination did not have a positive or detrimental impact on cognitive function or fatigue. INTERPRETATION: Non-hospitalized COVID-19 "long haulers" continue to experience neurologic symptoms, fatigue, and compromised quality of life 14.8 months after initial infection.