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Objective Covid‐19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid‐19. Methods We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid‐19 within a hospital network in Chicago, Illinois. We compared the severity of Covid‐19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression. Results Neurologic manifestations were present at Covid‐19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid‐19 (OR 4.02; 95% CI 2.04–8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968–0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0–2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11–0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001). Interpretation Neurologic manifestations occur in most hospitalized Covid‐19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

Objective Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”. Methods This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive (SARS‐CoV‐2+) and 50 laboratory‐negative (SARS‐CoV‐2‐) individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments. Results Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01). Interpretation Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.

Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA). Using a single-center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results. Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening-cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01). Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use.

Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4 T cell responses and diminished CD8 memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8 T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction. We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

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.

To compare demographics, comorbidities, neurologic symptoms, quality of life, and cognitive outcomes among adult individuals with neurologic manifestations of post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) across countries with varying income levels: the United States (U.S.), Colombia, Nigeria, and India. In this multi-country observational study, participants were evaluated in hospital clinics and recruited from institutional databases between 2020 and 2025. Patients were categorized as post-hospitalization Neuro-PASC (PNP) or non-hospitalized Neuro-PASC (NNP). Cognitive assessments were performed using the NIH Toolbox (U.S. and Colombia), the Montreal Cognitive Assessment (Nigeria), or the Mini-Mental State Examination (India). A total of 3,157 participants were enrolled (652 PNP; 2,505 NNP). PNP patients were predominantly male except in the US, while NNP patients were predominantly female, except in India. The most frequent neurologic symptoms were brain fog, myalgia, dizziness, headache, and sensory disturbances, with frequency highest in the U.S. and lowest in India. There were significant differences for most neurologic and non-neurologic symptoms of PASC, driven by higher frequencies in U.S. and Colombia in both PNP and NNP cohorts. In addition, cognitive impairment measured with different instruments varied across countries for both PNP and NNP groups. Multiple correspondence analysis showed clustering of symptom burden between U.S./Colombia and Nigeria/India. Neuro-PASC presents globally but symptom burden, and psychological distress vary across regions, likely influenced by sociocultural factors, healthcare access, and diagnostic tools. These findings highlight the need for culturally-adapted screening and post-COVID care worldwide.

Background Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects 14 million people in the US. Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating. However, the evolution of these symptoms and factors associated with recovery are poorly understood. This study aimed to characterize Neuro-PASC symptom evolution using a mobile phone application and assess user experience. Methods The Neuro-COVID Recovery Care Companion (NCRCC) mobile application consists of questionnaires integrated within Northwestern Medicine’s online MyChart platform which interfaces with the electronic medical record. Neuro-PASC patients completed daily surveys of twelve Neuro-PASC symptoms and their perceived percent recovery compared to their pre-COVID baseline. Patients also completed Patient-Reported Outcomes Measurement Information System (PROMIS) quality-of-life (QoL) surveys and NIH toolbox cognitive assessments at baseline and at 3-month follow up. Participants were retrospectively classified as “Improvers” or “Non-Improvers” based on the slope and range of their percent subjective recovery. Results Data from 63 participants presenting an average of 12.7 months after symptom onset were analyzed, including 27 (42.9%) Improvers and 36 (57.1%) Non-Improvers. Fewer women were Improvers (50% vs 75.7%; p  = 0.04). Multiple correspondence analysis showed that patients presenting with a constellation of anosmia, dysgeusia, and a lack of insomnia ( p  = 0.023) were less likely Improvers. Improvers had more fluctuations in their subjective recovery than Non-Improvers with greater mean variance (7.01 vs 3.79; p  = 0.0004) and positive recovery slope (5.84 vs 0; p  < 0.0001). There were no differences in QoL and cognition at initial assessment, but Improvers showed a trend toward increased processing speed and decreased sleep disturbance after 3 months. Both groups found the NCRCC application easy-to-use, useful, and satisfactory. Conclusions Our findings reveal previously unrecognized fluctuations in subjective recovery of Neuro-PASC, and that women and patients presenting with anosmia and dysgeusia are less likely to improve one year from COVID-19 onset. We found broad alterations in QoL in both groups suggesting that strategies to reduce sleep disturbance and improve cognition may contribute to subjective improvement. Our results suggest similar mobile applications may benefit patients with other ill-defined chronic diseases, by equipping and empowering them on their often windy road to recovery.

A trade-off between survival to sexual maturity and mating success is common across alternative reproductive tactics (ARTs), and can lead to tactical disruptive selection on shared traits (i.e. positive selection gradient in one tactic, and negative selection gradient in another). We were interested in examining the theoretical possibility of tactical disruptive selection on intrinsic growth rate. The male ARTs in Xiphophorus multilineatus express two distinct life histories: “courters” optimize mating success by maturing later at larger size and coaxing females to mate, while “sneakers” optimize survival to sexual maturity by maturing earlier at a smaller size, using both coaxing and coercive mating behaviors. In addition to differences in mating behaviors, body length, body depth, and the pigment pattern vertical bars, courter males grow faster than sneaker males. We present a new hypothesis for differences in growth rates between genetically influenced ARTs. The “growth-maturity optimization” hypothesis suggests that ARTs with differences in the probability of surviving to sexual maturity may have different optimal growth rates, leading to tactical disruptive selection. We also present a simple model to suggest that when considering both a cost and benefit to faster growth, tactical disruptive selection on growth rates is theoretically possible. In our model, the value that determines when tactical disruptive selection on growth rate will occur is the increase in probability of survival to sexual maturity gained through faster growth multiplied by the cost of faster growth (reduced longevity). Finally, we present empirical evidence to support the prediction that faster growth has a cost in X. multilineatus: in a controlled laboratory setting, courter males that did not survive 1.2 years past sexual maturity grew faster as juveniles (14–70 days) than those that survived.

[This corrects the article DOI: 10.3389/fimmu.2023.1155770.].[This corrects the article DOI: 10.3389/fimmu.2023.1155770.].

As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain–Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.