Navigating the Neurological Aftermath of COVID-19: An In-Depth Exploration (preprint)

Background: The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people and can result in both immediate and prolonged neurological effects, including severe complications. While numerous studies have explored the occurrence and consequences of neurological issues in COVID-19, they have often involved limited sample sizes. Purpose: This paper aims to determine the overall occurrence of neurological complications in COVID-19, examine their links with patient demographics, and assess their impact on patient outcomes. Additionally, it seeks to provide an overview of the current understanding of the underlying mechanisms. Methodology: Two systematic reviews were conducted to investigate acute and chronic neurological complications associated with COVID-19. A comprehensive search of medical databases was performed, and relevant studies were evaluated following PRISMA guidelines. Meta-analysis was carried out using the Mantel-Haenszel method, with subgroup analysis and meta-regression used to assess heterogeneity. Results: The analysis of acute complications included 20,011 patients with an average age of 58.1 years and a slight male predominance (55.2%). Common neurological symptoms included loss of taste and smell, headaches, acute encephalopathy, and stroke. For the analysis of long-term complications, 2,094 patients were included. Survivors of COVID-19 experienced ongoing neurological issues ranging from sensory impairments to fatigue, headaches, strokes, and even cognitive and psychiatric problems. Conclusion: By examining various neurological symptoms, this study found a significant association between these manifestations and worse overall outcomes, especially in patients over 60 years old. Identifying high-risk individuals and maintaining a high level of suspicion are crucial for enhancing our understanding of the underlying mechanisms, validating biomarkers, and improving the management of these neurological issues.

Brain infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern is a severe outcome in K18-hACE2 transgenic mice (preprint)

Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type, Delta, and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung and brain of these animals. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: We established that Wild-type, Delta, and Omicron infect the lung and brain of K18-hACE2 mice. At 3 dpi, mice infected with the Omicron variant show lower levels of viral RNA than those infected with Wild-type or Delta in the lung and brain. However, they still demonstrate upregulation of cytokines and chemokines, indicating that the Omicron variant can induce pulmonary and neuronal inflammation despite reduced viral proliferation after infection. At the humane endpoint/8dpi, there is a significant increase in viral RNA in mice infected with the Wild-type or Delta variant brains. However, viral RNA levels in Omicron-infected mice did not increase significantly as compared to 3dpi, and the expression of cytokines and chemokines in the brain, olfactory bulb, and medulla oblongata was downregulated, suggesting that infection by the Omicron variant results in attenuated neuroinflammation as compared with Wild-type and Delta.

Epileptic seizure and electroencephalographic characteristics of adult COVID-19 inpatients during the Omicron outbreak in China: a single center retrospective study (preprint)

Background This retrospective analysis assessed the characteristics of epileptic seizure and continuous electroencephalogram (CEEG) data in hospitalized patients diagnosed with COVID-19 during the Omicron outbreak.Methods CEEG was performed in 28 patients, with 17 showing unexplained altered mental status and 11 suspected of having seizures. Demographic and clinical variables, imaging results, outcomes, and comorbidities were collected.Results In total, 1,405 patients with COVID-19 infection were admitted during the study period. The proportion of patients who required intensive care unit (ICU) care and the in-hospital mortality was 16.3% and 7.8%, respectively. Among patients who underwent CEEG monitoring, 11 were in ICU, and 17 were in regular wards. Of these, 8 patients (28.5%) had severe COVID-19, whereas 6 had acute neuroimaging findings. EEG findings were not specific, with 7 patients (25%) having normal EEG results. Furthermore, 11 (39.3%) had benign EEG alterations, 6 (21.4%) had malignant, and 4 (14.3%) had highly malignant. Six patients exhibited epileptiform abnormalities, including 1 with a prior epilepsy history. Moreover, 4 patients experienced electrographic seizures, with 2 manifesting as epilepsia partialis continua and 2 as nonconvulsive status epilepticus. Periodic and rhythmic patterns were observed in 2 patients, spike-and-wave in 1 patient and generalized rhythmic delta activity in another patient. EEG attenuation without reactivity was seen in 4 patients.Conclusions Seizures can manifest as early symptoms in individuals infected with the Omicron variant of COVID-19. Despite the increased contagiousness associated with Omicron, we observed a higher prevalence of normal EEG results. This suggested that the Omicron variant may be associated with a lower likelihood of causing encephalitis or encephalopathy compared to other variants.

Post-traumatic Stress and Depressive Sequelae in ICU Hospitalized COVID-19 Patients 6 Months after Discharge: A Comparison with Non-COVID ICU Patients (preprint)

The Coronavirus Disease 2019 (COVID-19) pandemic has had a major impact on the mental and physical health of hospitalized patients. In our study we focused on the onset of symptoms correlated with Post-traumatic stress disorder (PTSD), depression and physical disabilities in patients admitted to the Intensive Care Unit (ICU) because of a severe respiratory distress related to COVID-19 (COVID Group) compared with patients admitted to the same ICU for trauma and other medical conditions than COVID-19 (No-COVID Group). The physical symptoms and the level of disability were evaluated with the Glasgow Outcome Scale-Extended (GOS-E), the Quality of Life after Brain Injury (QOLIBRI) and the 3 levels version of EQ-5D (EQ-5D-3L) questionnaire; psychiatric symptoms were investigated using the Impact of Event Scale-Revised 22-item (IES-R), the Patient Health Questionnaire, 9-Item Version (PHQ-9) and the Generalized Anxiety Disorder Assessment, 7-items version (GAD-7). These questionnaires were administered 6 months after discharge. Patients in the No-COVID Group showed statistically significant more severe scores in all the physical assessments while similar relevant PTSD and depressive symptoms were reported in both groups. The results of the present study underline the psychopathological impact of being hospitalized in ICU because of COVID-19 even after 6 months from discharge ,suggesting the importance of assessing the psychiatric effects of COVID-19 in the long term in order to create supportive measures.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Pathogenesis and Management of Acute Necrotizing Encephalopathy.

INTRODUCTION: During the COVID-19 pandemic, many cases of acute necrotizing encephalopathy (ANE) secondary to COVID-19 have been reported. ANE is characterized by a rapid onset, a fulminant course, and low morbidity and fatality rates. Therefore, clinicians need to be vigilant for such disorders, especially during the influenza virus and COVID-19 epidemics. AREAS COVERED: The authors summarize the most recent studies on the clinical spectrum and treatment essentials of ANE to provide references for prompt diagnosis and improved treatment of this rare but fatal disease. EXPERT OPINION: ANE is a type of necrotizing lesion of the brain parenchyma. There are two major types of reported cases. One is isolated and sporadic ANE, which is primarily caused by viral infections, particularly influenza and HHV-6 virus. The other type is familial recurrent ANE, which is caused by RANBP2 gene mutations. ANE patients have rapid progression and a very poor prognosis, with acute brain dysfunction occurring within days of viral infection and requiring admission to the intensive care unit. Clinicians still need to investigate and find solutions for the problems of early detection and treatment of ANE.

Analysis of risk factors for seizures and short-term reoccurrence of seizures in febrile children with SARS-CoV-2 infection: an observational study (preprint)

Background:With the epidemic of the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) variant Omicron, its accompanying neurological manifestations have gradually attracted attention.The main objective of this study was to compare seizures in febrile children with and without coronavirus disease 2019(COVID-19) and to conduct a short-term follow-up in the COVID-19 positive group to investigate the risk factors for short-term recurrence of seizures in children with febrile seizures(FS). Methods: Retrospective analysis of patients admitted to the Children's Hospital of Chongqing Medical University for fever and seizures between October 1 and December 30, 2022.Based on the results of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the patients were divided into a COVID-19 positive group and a COVID-19 negative group.Moreover,we followed up patients in the COVID-19-positive group for 3 months using outpatient or telephone follow-up, and the main content of follow-up included whether the patients had seizures after discharge and whether there were neurological abnormalities. Results:Compared with the COVID-19-negative group, the COVID-19-positive group had a higher proportion of seizure duration ≥ 15 minutes(18.7%VS5.1%;P=0.001), seizure ≥ 2 time(54.4%VS41.0%;P=0.024), status epilepticus(15.4%VS5.1%;P=0.005), and Electroencephalogram (EEG) abnormalities(29.4%VS13.6%;P=0.016).Seizures ≥2 time[P=0.015,OR(95% CI)=4.632(1.347-15.928)], peak temperature ≤39°C[P=0.001,OR(95% CI)=6.296(2.059-19.254)], and history of convulsions[P=0.005,OR(95% CI)=5.628(1.707-18.550)] were risk factors for recurrence of seizures within a short period of time in children with covid-19 infected febrile convulsions.In the COVID-19 positive group, three patients died and four patients had residual cognitive or motor dysfunction. Conclusions:The seizures were more severe in the COVID-19 positive group compared to the COVID-19 negative group.In addition, patients with COVID-19 who present with seizures and persistent impaired consciousness need to be alerted to serious neurological disorders such as acute necrotizing encephalopathy.

Nanomedicines for brain diseases: where we are and where we are going.

Graphical abstract [Formula: see text].

An unresponsive COVID-19 patient.

Neurological manifestations and complications are increasingly reported in coronavirus disease-19 (COVID-19) patients. Although pulmonary manifestations are more common, patients with severe disease may present with neurological symptoms such as in our case. We describe a case report of a 50-year-old male without previous known comorbidity who was found unresponsive due to COVID-19-related neurological complications. During this pandemic, an emergency radiologist should be well acquainted with various neurological manifestations of COVID-19. In this article, we will discuss the pathogenesis, imaging findings, and differentials of this disease.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Acute cerebellar ataxia during acute COVID-19: A case series and review of the literature.

Acute coronavirus disease 2019 (COVID-19)-associated cerebellar ataxia without multisystem inflammatory syndrome in children (MIS-C) or encephalopathy in children has been rarely reported. We reviewed medical records of hospitalized children who had developed cerebellar ataxia during the acute phase of COVID-19 infection, without MIS-C or encephalopathy, in our center. We also conducted a literature review and summarized the clinical characteristics, treatment, and outcomes. We found three cases in our center and additional three cases in the literature. All patients were male and five were preschool children. The cerebellar symptoms started between day 2 and day 10 during the acute phase of the COVID-19 infection. Two cases were complicated by mutism. One patient received therapy for acute cerebellar ataxia with corticosteroids, and others did not receive any specific therapy for acute cerebellar ataxia. The symptoms improved completely in all patients, with the recovery interval ranging from one week to two months. Further studies are warranted to elucidate the pathogenesis of acute cerebellar ataxia during acute COVID-19 in children.

SARS-COVID-19 TRIGGERED WERNICKE'S ENCEPHALOPATHY (CLINICAL CASE).

Patient P., born in 1956, was found by relatives in a state of confused consciousness, an act of involuntary urination and defecation, numbness and weakening of the strength of both lower limbs were recorded. He was taken by ambulance to the reception room of the Regional Clinical Center of Neurosurgery and Neurology. The following concomitant diseases are known from the life anamnesis: Atrial fibrillation, gout, hypertension and type II non-insulin-dependent diabetes mellitus. Objective status: general condition of medium severity, tophuses of small joints of hands and feet, knee and elbow joints. Pronounced deformity of hands and feet due to gouty lesions. Heart tones are weakened. Breath sounds are weakened. The abdomen is soft, not painful on palpation. Glasgow coma scale 14-15 points. Consciousness is confused, disoriented in time, space and own person. To clarify the diagnosis, clinical and laboratory and instrumental diagnostic methods were used. Neurological complications, in particular, acute encephalopathy, on the background of coronavirus infection, may develop in patients with the presence of such risk factors as advanced age, cardiovascular diseases, hypertension, diabetes, gout. Most of the neurological complications in COVID-19 are probably not related to the direct penetration of the virus into the CNS, but are a trigger for the development of the pathology. Neuroimaging in such cases does not reveal pathological changes or reflects non-specific disorders.

Acute necrotising encephalopathy: A rare complication providing a clue for the outbreak of H1N1 among medical students in Kanpur, India.

Kanpur, India, recently witnessed an outbreak of undifferentiated febrile illness among medical students. Several students developed high-grade fever with altered sensorium within 2-3 days after the index case. Surprisingly, this outbreak coincided with the death of several pigs in the vicinity. Acute necrotising encephalitis, although rare, was noted in some patients. When correlated with each other, all of these incidents were suggestive of an outbreak of H1N1.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program.

BACKGROUND: Compared to white individuals, Black and Hispanic individuals have higher rates of COVID-19 hospitalization and death. Less is known about racial/ethnic differences in post-acute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: Examine racial/ethnic differences in potential PASC symptoms and conditions among hospitalized and non-hospitalized COVID-19 patients. DESIGN: Retrospective cohort study using data from electronic health records. PARTICIPANTS: 62,339 patients with COVID-19 and 247,881 patients without COVID-19 in New York City between March 2020 and October 2021. MAIN MEASURES: New symptoms and conditions 31-180 days after COVID-19 diagnosis. KEY RESULTS: The final study population included 29,331 white patients (47.1%), 12,638 Black patients (20.3%), and 20,370 Hispanic patients (32.7%) diagnosed with COVID-19. After adjusting for confounders, significant racial/ethnic differences in incident symptoms and conditions existed among both hospitalized and non-hospitalized patients. For example, 31-180 days after a positive SARS-CoV-2 test, hospitalized Black patients had higher odds of being diagnosed with diabetes (adjusted odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.50-2.56, q<0.001) and headaches (OR: 1.52, 95% CI: 1.11-2.08, q=0.02), compared to hospitalized white patients. Hospitalized Hispanic patients had higher odds of headaches (OR: 1.62, 95% CI: 1.21-2.17, q=0.003) and dyspnea (OR: 1.22, 95% CI: 1.05-1.42, q=0.02), compared to hospitalized white patients. Among non-hospitalized patients, Black patients had higher odds of being diagnosed with pulmonary embolism (OR: 1.68, 95% CI: 1.20-2.36, q=0.009) and diabetes (OR: 2.13, 95% CI: 1.75-2.58, q<0.001), but lower odds of encephalopathy (OR: 0.58, 95% CI: 0.45-0.75, q<0.001), compared to white patients. Hispanic patients had higher odds of being diagnosed with headaches (OR: 1.41, 95% CI: 1.24-1.60, q<0.001) and chest pain (OR: 1.50, 95% CI: 1.35-1.67, q < 0.001), but lower odds of encephalopathy (OR: 0.64, 95% CI: 0.51-0.80, q<0.001). CONCLUSIONS: Compared to white patients, patients from racial/ethnic minority groups had significantly different odds of developing potential PASC symptoms and conditions. Future research should examine the reasons for these differences.

SARS-CoV-2 alters neural synchronies in the brain with more severe effects in younger individuals.

Coronavirus disease secondary to infection by SARS-CoV-2 (COVID19 or C19) causes respiratory illness, as well as severe neurological symptoms that have not been fully characterized. In a previous study, we developed a computational pipeline for the automated, rapid, high-throughput and objective analysis of electroencephalography (EEG) rhythms. In this retrospective study, we used this pipeline to define the quantitative EEG changes in patients with a PCR-positive diagnosis of C19 (n = 31) in the intensive care unit (ICU) of Cleveland Clinic, compared to a group of age-matched PCR-negative (n = 38) control patients in the same ICU setting. Qualitative assessment of EEG by two independent teams of electroencephalographers confirmed prior reports with regards to the high prevalence of diffuse encephalopathy in C19 patients, although the diagnosis of encephalopathy was inconsistent between teams. Quantitative analysis of EEG showed distinct slowing of brain rhythms in C19 patients compared to control (enhanced delta power and attenuated alpha-beta power). Surprisingly, these C19-related changes in EEG power were more prominent in patients below age 70. Moreover, machine learning algorithms showed consistently higher accuracy in the binary classification of patients as C19 versus control using EEG power for subjects below age 70 compared to older ones, providing further evidence for the more severe impact of SARS-CoV-2 on brain rhythms in younger individuals irrespective of PCR diagnosis or symptomatology, and raising concerns over potential long-term effects of C19 on brain physiology in the adult population and the utility of EEG monitoring in C19 patients.