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1.
researchsquare; 2024.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3955556.v1

ABSTRACT

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong’s intensive COVID-19 containment policy through 2020–2021 permitted us to identify sera from a small number of infection naïve individuals who received 3 doses RNA vaccine BNT162b2 of vaccines encoding the Wuhan-like spike who were boosted with a fourth dose monovalent Wuhan-like (WT) vaccine or the bivalent Wuhan-like and BA.4/5 spike (WT + BA.4/5) expressing vaccine. While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.


Subject(s)
COVID-19 , Breakthrough Pain , Seizures
2.
researchsquare; 2024.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3932956.v1

ABSTRACT

Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague‒Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1β, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1β/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.


Subject(s)
COVID-19 , Epilepsy , Nerve Degeneration , Adenomatous Polyposis Coli , Seizures
3.
researchsquare; 2024.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3928486.v1

ABSTRACT

Purpose: The COVID-19 pandemic caused rapid shifts in the workflow of many health services, but evidence of how this affected multidisciplinary care settings is limited. We propose a Process Mining approach that utilises timestamped data from Electronic Health Records to compare care provider patterns across pandemic waves.  Methods: We collected routine events from Scottish hospital episodes in adults with COVID-19 status and linked health provider inputs to generate standardised treatment logs. Conformance checking metrics were used to select the optimal model (Inductive Miner infrequent [IMi]) for downstream analysis. Visual diagrams from the discovered Petri Nets indicated the interactions on pre-coded provider and activity-level subsets. We used cross-log conformance checking and graph similarity to measure distances between adverse and less adverse groups across pandemic waves.  Results: We included 1,153 patients with COVID-19 (302 [26%] in Wave 1 and 851 [74%] in Wave 2) with 55,212 relevant care provider events. At the conformance checking stage, the IMi model, achieved good log fitness (LF=0.95) and generalisation (G=0.89), but limited precision (PR=0.27) across all granularity levels. More structured care procedures in Wave 1 were present, compared to mixed multidisciplinary patterns in Wave 2. Care activities differed in patients with extended stay (GED=348, PR=0.231 vs GED=197, PR=0.429 in shorter stays). Patients in out-of-hours care and intensive therapy were linked with more standardised patterns.  Conclusion: Process Mining can be incorporated alongside clinical oversight to provide visual and quantitative comparisons of care interactions in COVID-19 episodes and enhance further research in complex cases.


Subject(s)
COVID-19 , Seizures
4.
authorea preprints; 2024.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.170670149.94256463.v1

ABSTRACT

Objectives: To test the prevalence and evolution of acute olfactory and gustatory functional impairment and of their morphologic correlates in COVID-19 patients who require hospitalization due to COVID-19-related respiratory conditions. Key-words: COVID-19, taste, olfaction, electrogustometry, contact endoscopy Design: Electrogustometric (EGM) - thresholds at the tongue area supplied by the chorda tympani, at the soft palate and at the vallate papillae area were recorded bilaterally. Olfaction was examined by Sniffin’ sticks. The patients’ nasal and oral mucosa (fungiform papillae, fpap) were examined by contact endoscopy. Setting: Tertiary referral medical centre. Patients: 53 consecutive hospitalized patients (23 males, 30 females, age 42,54 ± 10, 95 yrs) with RT-PCR-confirmed COVID-19 diagnosis were included. Patients have been examined twice: just after hospital discharge and 4-6 weeks later. Main outcome measures: EGM-thresholds and taste strips, Schniffin-Sticks, Contact-Endoscopyesults: EGM-thresholds in patients were significantly higher at both instances than those of healthy subjects. EGM-thresholds at the second measurement were significantly lower than those at the first measurement. Accordingly, patient-reported gustatory outcomes were improved at the second measurement. The same pattern has been found using Sniffin’ sticks. Significant alterations in form and vascularization of fPap have been detected in patients, especially at the first instance. Conclusions: COVID-19 affects both gustatory and olfactory functions. It also affects in parallel the structure and vascularization of both nasal and oral mucosa, although the nasal mucosa to a much less, non-significant, extent. Our findings suggest that COVID-19 may cause a mild to profound neuropathy of multiple cranial nerves.


Subject(s)
COVID-19 , Nervous System Diseases , Taste Disorders , Seizures
5.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.12.18.572180

ABSTRACT

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble alpha-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) frequently experience hyposmia. We previously hypothesized that alpha-synuclein and tau misprocessing could occur following host responses to microbial triggers. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19+ patients (n=22), individuals with Lewy body disease (e.g., PD and dementia with Lewy bodies (DLB; n=6)), Alzheimer disease (AD; n=3), other non-synucleinopathy-linked degenerative diseases (e.g., progressive supranuclear palsy (PSP; n=2) and multisystem atrophy (MSA; n=1)). Further, we included neurologically healthy controls (HCO; n=9) and those with an inflammation-rich brain disorder as neurological controls (NCO; n=7). When probing for inflammatory changes focusing on anterior olfactory nuclei (AON) using anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, inflammation on average was not significantly altered in COVID19+ patients relative to controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-alpha-Syn and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes, when present, in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19+ patients.


Subject(s)
Parkinson Disease , Lewy Body Disease , Neurodegenerative Diseases , COVID-19 , Tauopathies , Supranuclear Palsy, Progressive , Dementia , Encephalitis , Inflammation , Severe Acute Respiratory Syndrome , Alzheimer Disease , Multiple System Atrophy , Seizures
6.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.12.05.570076

ABSTRACT

Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.


Subject(s)
Severe Acute Respiratory Syndrome , Seizures
7.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.11.30.23299240

ABSTRACT

Genomic surveillance of pathogen evolution is essential for public health response, treatment strategies, and vaccine development. In the context of SARS-COV-2, multiple models have been developed including Multinomial Logistic Regression (MLR) describing variant frequency growth as well as Fixed Growth Advantage (FGA), Growth Advantage Random Walk (GARW) and Piantham parameterizations describing variant Rt. These models provide estimates of variant fitness and can be used to forecast changes in variant frequency. We introduce a framework for evaluating real-time forecasts of variant frequencies, and apply this framework to the evolution of SARS-CoV-2 during 2022 in which multiple new viral variants emerged and rapidly spread through the population. We compare models across representative countries with different intensities of genomic surveillance. Retrospective assessment of model accuracy highlights that most models of variant frequency perform well and are able to produce reasonable forecasts. We find that the simple MLR model provides ~0.6% median absolute error and ~6% mean absolute error when forecasting 30 days out for countries with robust genomic surveillance. We investigate impacts of sequence quantity and quality across countries on forecast accuracy and conduct systematic downsampling to identify that 1000 sequences per week is fully sufficient for accurate short-term forecasts. We conclude that fitness models represent a useful prognostic tool for short-term evolutionary forecasting.


Subject(s)
Refractive Errors , Seizures
8.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.10.13.23296903

ABSTRACT

Importance Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective To conduct near-real-time monitoring of health outcomes following COVID-19 vaccination in the United States (US) pediatric population aged 6 months to 17 years. Design We evaluated 21 pre-specified health outcomes; 15 were sequentially tested through near-real-time surveillance, and 6 were monitored descriptively within a cohort of vaccinated children. We tested for increased rate of each outcome following vaccination compared to a historical comparator cohort. Setting This population-based study was conducted under the US Food and Drug Administration public health surveillance mandate using three commercial claims databases. Participants Children aged 6 months to 17 years were included if they received a monovalent COVID-19 vaccine dose before early 2023 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination dose. Exposure Exposure was defined as receipt of a monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose. The primary analysis evaluated dose 1 and dose 2 combined, and secondary analyses evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk window, end of study period, or a subsequent dose administration. Main Outcomes Twenty-one prespecified health outcomes. Results The study included 4,102,016 enrollees aged 6 months to17 years. Thirteen of 15 outcomes sequentially tested did not meet the threshold for a statistical signal. In the primary analysis, myocarditis or pericarditis signals were detected following BNT162b2 vaccine in children aged 12-17 years old and seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates. Conclusions and Relevance Of the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously published reports. The new signal detected for seizures/convulsions among younger children should be further investigated in a robust epidemiological study with better confounding adjustment.


Subject(s)
Pericarditis , COVID-19 , Seizures , Myocarditis
9.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.09.07.556636

ABSTRACT

In September 2023, the SARS-CoV-2 XBB descendants, such as XBB.1.5 and EG.5.1 (originally XBB.1.9.2.5.1), are predominantly circulating worldwide. Unexpectedly, however, a lineage distinct from XBB was identified and named BA.2.86 on August 14, 2023. Notably, BA.2.86 bears more than 30 mutations in the spike (S) protein when compared to XBB and the parental BA.2, and many of them are assumed to be associated with immune evasion. Although the number of reported cases is low (68 sequences have been reported as of 7 September 2023), BA.2.86 has been detected in several continents (Europe, North America and Africa), suggesting that this variant may be spreading silently worldwide. On 17 August 2023, the WHO designated BA.2.86 as a variant under monitoring. Here we show evidence suggesting that BA.2.86 potentially has greater fitness than current circulating XBB variants including EG.5.1. The pseudovirus assay showed that the infectivity of BA.2.86 was significantly lower than that of B.1.1 and EG.5.1, suggesting that the increased fitness of BA.2.86 is not due to the increased infectivity. We then performed a neutralization assay using XBB breakthrough infection sera to address whether BA.2.86 evades the antiviral effect of the humoral immunity induced XBB subvariants. The 50% neutralization titer of XBB BTI sera against BA.2.86 was significantly (1.4-fold) lower than those against EG.5.1. The sera obtained from individuals vaccinated with 3rd-dose monovalent, 4th-dose monovalent, 4th-dose BA.1 bivalent, and 4th-dose BA.5 bivalent mRNA vaccines exhibited very little or no antiviral effects against BA.2.86. Moreover, the three monoclonal antibodies (Bebtelovimab, Sotrovimab and Tixagevimab), which worked against the parental BA.2, did not exhibit antiviral effects against BA.2.86. These results suggest that BA.2.86 is one of the most highly immune evasive variants ever.


Subject(s)
Seizures
10.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.09.23293901

ABSTRACT

Objective: To characterize subphenotypes of self-reported symptoms and outcomes(SRSOs) in Post-acute sequelae of COVID-19(PASC). Design: Prospective, observational cohort study of PASC subjects. Setting: Academic tertiary center from five clinical referral sources. Participants: Adults with COVID-19 [≥] 20 days before enrollment and presence of any new self-reported symptoms following COVID-19. Exposures: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardized assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning, and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via qPCR. Primary and Secondary outcomes of measure: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA), and relationship between viral load with SRSOs and PASC subphenotypes. Results: Baseline data for 214 individuals were analyzed. The study visit took place at a median of 197.5 days after COVID-19 diagnosis, and participants reported ever having a median of 9/16 symptoms (interquartile range 6-11) after acute COVID, with muscle-aches, dyspnea, and headache being the most common. Fatigue, cognitive impairment, and dyspnea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3, interquartile range 1-6) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically-active PASC subphenotypes: a high burden constitutional symptoms (21.9%) , a persistent loss/change of smell and taste (20.6%) , and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001). Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. Conclusions: We identified distinct PASC subphenotypes and highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.


Subject(s)
Headache , Pain , COVID-19 , Dyspnea , Sexual Dysfunctions, Psychological , Cognition Disorders , Seizures
11.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.07.26.550688

ABSTRACT

SARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.


Subject(s)
Seizures , Severe Acute Respiratory Syndrome
12.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.07.23.549423

ABSTRACT

Background: By the end of 2022, new variants of SARS-CoV-2, such as BQ.1.1.10, BA.4.6.3, XBB, and CH.1.1, emerged with higher fitness than BA.5. Methods: The file (spikeprot0304), which contains spike protein sequences, isolates collected before March, 4, 2023, was downloaded from Global Initiative on Sharing All Influenza Data (GISAID). A total of 188 different spike protein sequences were chosen, of which their isolates were collected from December 2022 to February 2023. These sequences did not contain undetermined amino acid X, and each spike protein sequence had at least 100 identical isolate sequences in GISAID. Phylogenetic trees were reconstructed using IQ-TREE and MrBayes softwares. A median-join network was reconstructed using PopART software. Selection analyses were conducted using site model of PAML software. Results: The phylogenetic tree of the spike DNA sequences revealed that the majority of variants belonged to three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. The median network showed that these lineages had at least six major diversifying centers. The spike DNA sequences of these diversifying centers had the representative accession IDs (EPI_ISL_) of 16040256 (BN.1.2), 15970311 (BA.5), 16028739 (BA.5.11), 16028774 (BQ.1), 16027638 (BQ.1.1.23), and 16044705 (XBB.1.5). Selection analyses revealed 26 amino-acid sites under positive selection. These sites included L5, V83, W152, G181, N185, V213, H245, Y248, D253, S255, S256, G257, R346, R408, K444, V445, G446, N450, L452, N460, F486, Q613, Q675, T883, P1162, and V1264. Conclusion: The spike proteins of SARS-CoV-2 from December 2022 to February 2023 were characterized by a swarm of variants that were evolved from three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. These lineages had at least six diversifying centers. Selection analysis identified 26 amino acid sites were under positive selection. Continued surveillance and research are necessary to monitor the evolution and potential impact of these variants on public health.


Subject(s)
Seizures
13.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202307.0921.v1

ABSTRACT

We provide a summary of various epidemiological parameters related to COVID-19 such as incubation period, serial interval and other parameters. Understanding these parameters is important for developing prevention strategies. SARS-CoV-2 can be transmitted by droplets and close contact, but there is evidence of airborne transmission. Aerosol-generating procedures have been identified as one of the specific risk factors for healthcare workers. Super-spreading events refer to situations where a small number of individuals cause the majority of infections. The basic reproductive number (R0) and the spread parameter (k) are used to characterise the transmissibility of the disease. Estimated values for R0 range from 2 to 3 and the estimated value for k is 0.1.The duration of infectiousness depends on viral load and shedding. Viral load varies according to factors such as clinical spectrum, type of variant and vaccination status. The relationship between viral load and infectivity is not fully understood.With regard to the frequency of symptoms and signs of COVID-19, fever, cough, fatigue and dyspnoea are common. The prevalence of olfactory and gustatory dysfunction (OGD) varies between studies and countries. Age and comorbidities are factors associated with olfactory dysfunction.Estimates of the proportion of asymptomatic patients range from 6% to 96%. Asymptomatic transmission is considered likely and is important for control measures.We reviewed the quantitative semiology of COVID-19 is reported on sensitivity, specificity and likelihood ratios of signs.Finally, we also review risk factors for COVID-19 (including health care workers), co-infections, and epidemiology of variants..


Subject(s)
COVID-19 , Cough , Fatigue , Coinfection , Fever , Seizures
14.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3113656.v1

ABSTRACT

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.


Subject(s)
COVID-19 , Status Epilepticus , Brain Diseases , Epilepsy , Encephalitis , Epilepsia Partialis Continua , Landau-Kleffner Syndrome , Seizures
15.
Med Lav ; 114(3): e2023028, 2023 Jun 12.
Article in English | MEDLINE | ID: covidwho-20232123

ABSTRACT

BACKGROUND: Italy had a persistent excess of total mortality up to July 2022. This study provides updated estimates of excess mortality in Italy until February 2023. METHODS: Mortality and population data from 2011 to 2019 were used to estimate the number of expected deaths during the pandemic. Expected deaths were obtained using over-dispersed Poisson regression models, fitted separately for men and women, including calendar year, age group, and a smoothed function of the day of the year as predictors. The excess deaths were then obtained by calculating the difference between observed and expected deaths and were computed at all ages and working ages (25-64 years). RESULTS: We estimated 26,647 excess deaths for all ages and 1248 for working ages from August to December 2022, resulting in a percent excess mortality of 10.2% and 4.7%, respectively. No excess mortality was detected in January and February 2023. CONCLUSIONS: Our study indicates substantial excess mortality beyond those directly attributed to COVID-19 during the BA.4 and BA.5 Omicron wave in the latter half of 2022. This excess could be attributed to additional factors, such as the heatwave during the summer of 2022 and the early onset of the influenza season.


Subject(s)
COVID-19 , Male , Humans , Female , Italy , Pandemics , Seizures
16.
Med J Malaysia ; 78(3): 421-426, 2023 05.
Article in English | MEDLINE | ID: covidwho-20235551

ABSTRACT

OBJECTIVES: Severe, acute, respiratory syndromecoronavirus- 2 (SARS-CoV-2) infections can be complicated by central nervous system (CNS) disease. One of the CNS disorders associated with Coronavirus Disease-19 (COVID- 19) is posterior reversible encephalopathy syndrome (PRES). This narrative review summarises and discusses previous and recent findings on SARS-CoV-2 associated PRES. METHODS: A literature search was carried out in PubMed and Google Scholar using suitable search terms and reference lists of articles found were searched for further articles. RESULTS: By the end of February 2023, 82 patients with SARS-CoV-2 associated PRES were recorded. The latency between the onset of COVID-19 and the onset of PRES ranged from 1 day to 70 days. The most common presentations of PRES were mental deterioration (n=47), seizures (n=46) and visual disturbances (n=18). Elevated blood pressure was reported on admission or during hospitalisation in 48 patients. The most common comorbidities were arterial hypertension, diabetes, hyperlipidemia and atherosclerosis. PRES was best diagnosed by multimodal cerebral magnetic resonance imaging (MRI). Complete recovery was reported in 35 patients and partial recovery in 21 patients, while seven patients died. CONCLUSIONS: PRES can be a CNS complication associated with COVID-19. COVID-19 patients with mental dysfunction, seizures or visual disturbances should immediately undergo CNS imaging through multimodal MRI, electroencephalography (EEG) and cerebrospinal fluid (CSF) studies in order not to miss PRES.


Subject(s)
COVID-19 , Hypertension , Posterior Leukoencephalopathy Syndrome , Humans , Posterior Leukoencephalopathy Syndrome/diagnosis , Posterior Leukoencephalopathy Syndrome/etiology , SARS-CoV-2 , COVID-19/complications , Seizures/etiology , Electroencephalography/adverse effects , Electroencephalography/methods , Hypertension/complications , Magnetic Resonance Imaging/methods
17.
J Clin Neurophysiol ; 39(2): 159-165, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-20241329

ABSTRACT

PURPOSE: Neurologic manifestations of coronavirus disease (COVID-19) such as encephalopathy and seizures have been described. To our knowledge, detailed EEG findings in COVID-19 have not yet been reported. This report adds to the scarce body of evidence. METHODS: We identified eight COVID-19 positive patients who underwent EEG monitoring in our hospital system. RESULTS: EEGs were most commonly ordered for an altered level of consciousness, a nonspecific neurologic manifestation. We observed generalized background slowing in all patients and generalized epileptiform discharges with triphasic morphology in three patients. Focal electrographic seizures were observed in one patient with a history of focal epilepsy and in another patient with no such history. Five of eight patients had a previous diagnosis of epilepsy, suggesting that pre-existing epilepsy can be a potential risk factor for COVID-19-associated neurological manifestations. Five of eight patients who underwent EEG experienced a fatal outcome of infection. CONCLUSIONS: Our findings underscore previous observations that neurologic manifestations are common in severe cases. COVID-19 patients with epilepsy may have an increased risk of neurological manifestations and abnormal EEG.


Subject(s)
COVID-19 , Epilepsies, Partial , Electroencephalography , Humans , SARS-CoV-2 , Seizures/diagnosis , Seizures/etiology
18.
Zhonghua Er Ke Za Zhi ; 61(6): 543-549, 2023 Jun 02.
Article in Chinese | MEDLINE | ID: covidwho-20241887

ABSTRACT

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.


Subject(s)
Brain Diseases , COVID-19 , Child , Female , Male , Humans , Retrospective Studies , Cytokine Release Syndrome , COVID-19/complications , SARS-CoV-2 , Brain Diseases/diagnosis , Brain Diseases/etiology , Prognosis , Seizures , Cytokines
19.
Pediatr Neurol ; 145: 148-153, 2023 08.
Article in English | MEDLINE | ID: covidwho-20230760

ABSTRACT

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.


Subject(s)
COVID-19 , Nervous System Diseases , Humans , Child , Infant, Newborn , Infant , Child, Preschool , Adolescent , COVID-19/complications , SARS-CoV-2 , Retrospective Studies , Headache , Seizures/complications , Nervous System Diseases/complications
20.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3009867.v1

ABSTRACT

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.


Subject(s)
COVID-19 , Status Epilepticus , Nervous System Diseases , Brain Diseases , Seizures, Febrile , Neurologic Manifestations , Fever , Cognition Disorders , Consciousness Disorders , Severe Acute Respiratory Syndrome , Seizures , Dermatofibrosarcoma
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