Sex and gender differences in adverse events following receipt of influenza and COVID-19 vaccination among healthcare workers (preprint)

IntroductionActive and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. We sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. MethodsThis cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination (DPV) for bivalent COVID-19 and Influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants experiences with AEs also were collected for the COVID-19 vaccine recipients. ResultsFemales were more likely to report local AEs after influenza (OR=2.28, p=0.001) or COVID-19 (OR=2.57, p=0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after influenza (OR=1.18, p=0.552) or COVID-19 (OR=0.96, p=0.907) vaccination. Exogenous hormones from birth control use did not impact the rates of reported AEs following COVID-19 vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. ConclusionsOur findings highlight the need for sex- and gender-inclusive policies to inform more effective occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers and to more fully characterize the post-vaccination behavioral differences between men and women. KEY MESSAGEO_ST_ABSWhat is already known on this topicC_ST_ABS{Rightarrow} Among diversely aged adults 18-64 years, females report more AEs to vaccines, including the influenza and COVID-19 vaccines, than males. {Rightarrow}Vaccine AEs play a role in shaping vaccine hesitancy and uptake. {Rightarrow}Vaccine uptake related to influenza and COVID-19 are higher among men than women. {Rightarrow}Research that addresses both the sex and gender disparities of vaccine outcomes and behaviors is lacking. What this study adds{Rightarrow} This prospective active reporting study uses both quantitative and qualitative survey data to examine sex and gender differences in AEs following influenza or COVID-19 vaccination among a cohort of reproductive-aged healthcare workers. How this study might affect research, practice, or policy{Rightarrow} Sex and gender differences in AEs and perceptions relating to vaccination should drive the development of more equitable and effective vaccine strategies and policies in occupational health settings.

EEG Findings in Coronavirus Disease.

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.

Increasing Local Disease Preparedness and Surveillance Capacity for Global Health Security: A Cluster-Randomised Control Trial (preprint)

Background: Low-income countries are often characterized by poor health infrastructures and lack systems needed to timely detect and control disease outbreaks, such as the 2014-16 Ebola Viral Disease and COVID-19. In such contexts, a “One Health” approach, which involves investing in both human and animal health systems, plausibly improves local health outcomes by enabling early detection of zoonotic diseases before they are transmitted to humans, and by timely triggering a health system response needed to mitigate possible outbreaks. There is an urgent call to translate One Health into action and create inclusive and sustainable policies. There is however limited direct evidence on the gains from One Health approaches. We contribute here by using a randomised intervention to assess the impact of a participatory community-based One Health program.Methods: As part of a cluster-randomised control trial, government and communities recruited, trained and installed Community Animal Health Workers (CAHWs) to work alongside Community Health Workers (CHWs) in 300 randomly selected rural villages in Sierra Leone. Another 63 villages were randomly selected as control sites and had CHWs exclusively. CAHWs provided essential animal health services, disseminated information regarding animal and human health best practices, and actively participated in surveillance efforts by reporting suspected disease symptoms to government supervisors. We investigated program impacts on human health as well as key intermediary outcomes, including animal health, animal and human health-related behaviours, integration into public services, and household wealth. The trial is registered at clinicaltrialregister.nl (# 21660) and OSF (https://osf.io/9xfv3).Findings: In July and August 2017, the community-based One Health program successfully recruited, trained and installed CAHWs across 287 villages. Throughout the program's duration, spanning from July 2017 to July 2019, the CAHWs reported on 17,813 suspected disease-related events. Using survey data from 2,538 respondents, collected in March and April 2020, we found no evidence of impacts on human health (-0.010 standard deviation units (SDU), 95% CI -0.131, 0.111). The program did improve intermediary outcomes including animal health (0.157 SDU, 95% CI 0.022, 0.293), animal husbandry practices (0.127 SDU, 95% CI -0.022, 0.276), human health behaviours (0.137 SDU, 95% CI -0.007, 0.281), integration into public services (0.300 SDU, 95% CI 0.116, 0.484), and households’ attitudes towards disease reporting (0.263 SDU, 95% CI 0.109, 0.418).Interpretation: Participatory community-based One Health interventions can increase preparedness against zoonotic diseases.Trial Registration: The trial is registered at clinicaltrialregister.nl (# 21660) and OSF (https://osf.io/9xfv3).Funding: The study was funded by NWO grant #451-14-001 and #VI.Vidi.191.154, ESRC grant ES/J017620/1, the Royal Netherlands Embassy in Ghana, the International Growth Center, New York University – Abu Dhabi and the World Bank REDISSE program.Declaration of Interest: We declare no competing interests.Ethical Approval: Before the onset of the program, formal approval was obtained from local authorities. We obtained verbal informed consent from all study participants. Ethics approval was obtained from the Office of the Sierra Leone Ethics and Scientific Review Committee (SLERC 16102017) and Columbia University (AAAR5175).

[Possibilities of optimizing therapy in COVID-19 survivors with focal epilepsy]. / Vozmozhnosti optimizatsii terapii u patsientov s fokal'noi epilepsiei, perenesshikh COVID-19.

OBJECTIVE: To study the effect of phenosanoic acid therapy on the frequency of seizures, asthenia and quality of life of adult patients with focal epilepsy who had a new coronavirus infection caused by SARS-CoV-2. MATERIAL AND METHODS: The data of 20 patients with focal epilepsy who suffered COVID-19 and received therapy with phenosanic acid (Dibufelon) were studied. The frequency of epileptic seizures, the severity of asthenia and the quality of life were evaluated according to clinical scales. RESULTS: Significant decrease in the frequency of bilateral tonic-clonic seizures and focal seizures with loss of consciousness was recorded. There was a significant improvement in the quality of life. There was no significant dynamics of asthenia against the background of taking the drug phenosanic acid in patients. CONCLUSION: The preparation of phenosanic acid can be an effective means of add-on therapy in patients with epilepsy who have undergone COVID-19.

Computational fitness estimates of SARS-CoV-2 mutations affecting spike protein binding to antibodies and ACE2 (preprint)

Predicting the impact of new emerging virus mutations is of major interest in surveillance and for understanding the evolutionary forces of the pathogen. The SARS-CoV-2 surface spike-protein (S-protein) binds to human ACE2 receptors as a critical step in host cell infection. At the same time, S-protein binding to human antibodies neutralizes the virus and prevents interaction with ACE2. Here we combine these two binding properties in a simple fitness model, using structure-based computation of all possible mutation effects averaged over 10 ACE2 complexes and 10 antibody complexes of the S-protein. The ACE2-antibody selectivity change caused by mutation (i.e., the change binding to ACE2 minus the change in binding to immunity-inducing antibodies) is proposed to be a key metric of virus fitness, which furthermore enables substantial systematic error cancelation when evaluated. In this model, new mutations become fixated if they increase the selective binding to ACE2 relative to circulating antibodies, assuming that both are present in the host in a competitive binding situation. We use this model to categorize viral mutations that may best reach ACE2 before being captured by antibodies. Our model may aid the understanding of variant-specific vaccines and molecular mechanisms of viral evolution in the context of a human host.

Immediate and 6-month seizure outcomes following first and second SARS-CoV2 mRNA vaccinations: A multicenter study with a nationwide survey.

OBJECTIVE: This study aimed to identify seizure outcomes in people with epilepsy (PWE) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) messenger RNA vaccination. METHODS: We examined PWE (n = 332, age ≥ 14 years) treated in four tertiary hospitals between 2021 and 2022 to assess the incidence of seizure worsening following vaccination using closed questions. We identified the clinical factors associated with worsening and 6-month vaccination outcomes. We also conducted a nationwide survey on self-reported seizure worsening using open questions, to which 261 general practitioners from 99 institutes contributed. RESULTS: Of the 282 PWE vaccinated in the four hospitals, 16 (5.7%) exhibited seizure worsening; most of them emerged within 48 h of vaccination and were not sustained. Thus, all PWE were at baseline condition 6 months after their vaccination. PWE with seizure worsening were more significantly associated with focal impaired awareness seizures (p < 0.001), high seizure frequency (p = 0.025), and drug-resistant epilepsy (p = 0.007) at baseline compared to PWE without worsening. Multivariate logistic regression analysis revealed that focal impaired awareness seizures were independently associated with worsening (odds ratio, 7.0; 95% confidence interval, 1.50-32.77). A nationwide survey of 5156 PWE data (real-world data) confirmed an extremely low incidence rate of self-reported seizure worsening (0.43%). SIGNIFICANCE: Some PWE, particularly refractory focal epilepsy, exhibit seizure worsening. However, the worsening events were infrequent, non-sustainable, and probably under-reported by PWE, suggesting that there is little evidence that worsening seizures discourage current and future vaccinations.

Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai older adults (preprint)

Introduction: Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy due to systemic reactogenicity among older adults. Objectives: To compare the immunogenicity and reactogenicity of fractional ID and standard intramuscular (IM) booster vaccination of mRNA-1273 and BNT162b2 vaccines in older adults. Methods: Participants aged [≥]65 years who previously vaccinated with 2-dose ChAdOx1 were randomized to receive one of the four booster vaccinations: 0.1mL ID mRNA-1273, 0.5mL IM mRNA-1273, 0.1mL ID BNT162b2 and 0.3mL IM BNT162b2. Immunogenicity as measured by anti-receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NAb) against Wuhan and Omicron BA.1, BA.2 and BA.4/5, and IFN{gamma}-producing cells. Local and systemic adverse effects (AEs) were self-reported via an electronic diary card. Results: Of the 210 participants enrolled, 70.5% were female and median age was 77.5 years (interquartile range (IQR): 71.0-84.0). Following the booster dose, both ID vaccination induced 37% lower levels of anti-RBD IgG than IM vaccination of the same vaccine. NAb against ancestral and Omicron BA.1 strains was highest following IM mRNA-1273 (1,718 and 617), followed by ID mRNA-1273 (1,212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN{gamma} responses were similar or higher in the ID groups when compared with their respective IM groups. Vaccine delivery through ID route tended to have lower systemic AEs, although more local AEs reported in ID mRNA-1273 group. Conclusions: Fractional ID vaccination induced immunogenicity and reactogenicity comparable to IM and may be an alternative option for older people.

Seizure Control in Patients with Epilepsy during the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Objective To investigate seizure control in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic. Method A systematic review and meta-analysis was conducted, and the MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies that reported seizure control in patients with epilepsy during the COVID-19 pandemic were included. Pooled proportions with 95% confidence intervals (CIs) of patients with epilepsy who experienced seizure worsening during the COVID-19 pandemic were assessed using a random-effects model. The quality of the assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Subgroup analyses were performed, excluding studies with reports of seizures worsening from caregivers. Results A total of 24 studies with 6,492 patients/caregivers were included in the meta-analysis. The pooled proportion of seizure worsening was 18.5% (95% CI: 13.9-23.6; I2=96%; p<0.01). The pooled proportion of seizure worsening in the subgroup analysis was 18.9% (95% CI: 13.5-25.0; I2=96%; p<0.01). Conclusion Although the heterogeneity was high, our results showed a relatively high incidence of seizure worsening during the COVID-19 pandemic. During the COVID-19 pandemic, physicians should be aware of the likelihood of worsening seizures in patients with epilepsy.

Should patients with epilepsy be vaccinated against coronavirus disease 2019? A systematic review and meta-analysis.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccination coverage, willingness, and safety profiles in patients with epilepsy remain poorly understood. We aimed to summarize the available evidence of COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. METHODS: We performed a literature search in the Pubmed, EMBASE, and Cochrane Central Register database between 1 January 2020 and 30 April 2022. We included eligible studies that provided information on the COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. We investigated the association between baseline characteristics of patients with epilepsy and unvaccination status using a fixed-effect model. We calculated the pooled overall willingness to be vaccinated against COVID-19. We systematically reviewed the safety profiles after COVID-19 vaccination in patients with epilepsy. RESULTS: Ten eligible observational studies and two case reports yielded 2589 participants with epilepsy or their caregivers. Among 2145 participants that provided the information of vaccination status, 1508 (70.3%) patients with epilepsy were not administered COVID-19 vaccine, and 58% (95%CI 40-75%) of respondents were willing to be vaccinated against COVID-19. Seizure status (active versus inactive, OR 1.84 95%CI 1.41-2.39, I2 = 0%) rather than seizure type (focal versus non-focal, OR 1.22 95%CI 0.94-1.58, I2 = 0%) was associated with COVID-19 unvaccination status. Vaccines were well-tolerated; epilepsy-related problems such as increase in seizure frequency and status epilepticus after COVID-19 vaccination were uncommon. CONCLUSIONS: Our findings suggest a low COVID-19 vaccination coverage and willingness in patients with epilepsy. Vaccination against COVID-19 appears to be well-tolerated and safe in patients with epilepsy, supporting a positive outlook toward vaccination in this population.

Safety and efficacy of two immunization schedules with an inactivated SARS-CoV-2 vaccine in adults. A randomized non-inferiority clinical trial. (preprint)

Background: Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac (Sinovac Life Sciences), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity in previous studies, preventing severe COVID-19 cases. We further investigated the safety and efficacy of two immunization schedules of CoronaVac in a non-inferiority trial in healthy adults. Methods: This is a multi-center and randomized clinical trial. Healthy adults were enrolled at eight centers in Chile. Participants were randomly assigned to two vaccination schedules, receiving two doses with either 14 (0-14) or 28 (0-28) days between each. 2302 participants were vaccinated. The primary safety and efficacy endpoints were solicited adverse events (AE) within 7 days after each dose and compared the number of cases of SARS-CoV-2 infection 14 days after the second dose between schedules, respectively. Findings: The most frequent local AE was pain at the injection site, which was less frequent in participants aged over 60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. The remaining AEs were minor allergic reactions and fever. Most AEs were mild and transient. There were no significant differences for local and systemic AE between schedules. No anaphylactic reactions or vaccine-related severe AEs were observed. 58 COVID-19 cases were confirmed, and all but two of them were mild. No differences were observed in protection between schedules. Interpretation: CoronaVac is safe, especially in over 60 years-old participants. Both schedules protected against COVID-19 hospitalizations. Funding: MINSAL, Chile, CPC & IMII, Chile.

[Telemedicine and epilepsy: healthcare experience of a national reference center during the COVID-19 pandemic]. / Telemedicina y epilepsia: experiencia asistencial de un centro de referencia nacional durante la pandemia de COVID-19.

INTRODUCTION: Countries worldwide are having to cope with the COVID-19 pandemic caused by SARS-CoV-2. The burden on their national health systems is currently at unprecedented levels. Telemedicine care was initiated at an early stage in our centre. PATIENTS AND METHODS: We conducted a descriptive and retrospective study to evaluate the usefulness of telemedicine during lockdown in our centre. Patients included in the study had a clinical diagnosis of epilepsy, with two visits via telemedicine, who had been followed up for at least six months during the normal situation prior to the COVID-19 pandemic and two face-to-face consultations during the same period. RESULTS: A total of 115 patients were included. The average age was 29 years, 53% were males, 52.2% had focal epilepsy, 58.3% with a structural causation and 57.4% had difficult-to-treat epilepsy. The mean number of seizures prior to lockdown was 9.73/month and 6.54/month during lockdown. The number of patients who were seizure-free when lockdown ended was higher than that observed in the phase before it began: 54 versus 45 out of 115. CONCLUSIONS: Telemedicine is a very useful strategy for monitoring the course, progress and therapeutic changes in epileptic patients in the short and medium term. The reduction in the seizure frequency can be sustained in the medium term, not only in the short term as corroborated in previous studies. Telemedicine allows access to virtually all patients and closer monitoring.

TITLE: Telemedicina y epilepsia: experiencia asistencial de un centro de referencia nacional durante la pandemia de COVID-19.Introducción. El mundo entero está afrontando la pandemia por COVID-19 causada por el SARS-CoV-2. Los sistemas de salud nacionales están sometidos a niveles de sobrecarga sin precedentes. En nuestro centro se inició de forma temprana la asistencia a través de telemedicina. Pacientes y métodos. Es un estudio descriptivo y retrospectivo para evaluar la utilidad de la telemedicina durante el confinamiento en nuestro centro. Se incluyó a los pacientes con diagnóstico clínico de epilepsia, con dos asistencias a través de telemedicina, que tuvieran seguimiento durante al menos seis meses durante la situación de normalidad previa a la pandemia por COVID-19 y dos consultas presenciales durante ese mismo período. Resultados. Se incluyó a 115 pacientes. La media de edad fue de 29 años, el 53% fueron varones, el 52,2% con epilepsia focal, el 58,3% de etiología estructural y el 57,4% presentaba epilepsia de difícil control. La media de crisis preconfinamiento fue de 9,73/mes y de 6,54/mes durante el confinamiento. El número de pacientes libres de crisis fue mayor al final del confinamiento respecto a la fase preconfinamiento, 54 frente a 45/115. Conclusiones. La telemedicina es una estrategia de mucha utilidad en la monitorización de la evolución, el control evolutivo y los cambios terapéuticos en pacientes epilépticos a corto y medio plazo. La reducción de la frecuencia de crisis puede mantenerse a medio plazo, no sólo a corto plazo como se corroboró en estudios previos. La telemedicina permite acceder a prácticamente la totalidad de los pacientes y realizar un seguimiento más cercano.

New Onset Focal Seizure Following COVID-19 Vaccination: Case Report (preprint)

Introduction: As more novel COVID-19 vaccines are being rolled out in a frantic pace globally, any complication that might be related to COVID-19 vaccines should be highlighted, especially since COVID-19 vaccines are relatively new, and side effects may yet to be fully elucidated. We report a case of a healthy 18-year-old male who presented with new onset focal seizures 5 days after receiving 1 st dose of Oxford/AstraZeneca COVID-19 vaccine. Case Presentation The patient was treated with intravenous phenytoin and oral levetiracetam 250mg twice daily with no further events. There was no documented fever. CT venogram and EEG were unremarkable. MRI brain revealed generalised atrophy including mild bilateral hippocampal atrophy with no evidence of sclerosis. There was no predilection for seizures identified from the patient’s history. The patient was discharged the following day on levetiracetam and advised to proceed with the 2 nd dose of Oxford/AstraZeneca COVID-19 vaccination in 3 months’ time. Conclusion: Seizures following COVID-19 vaccination have only been reported in a handful of cases. COVID-19 vaccination could lower seizure threshold, or unmask an underlying predisposition for epilepsy. As most COVID-19 vaccines worldwide are given in 2 doses, clinicians should consider maintaining patients on anti-seizure drugs if vaccination was thought to be a provoking factor.

Market Response to Disclosure of Corporate Social Responsibility (CSR) during the COVID-19 Pandemic (preprint)

This article aims to disclose the CSR on stock price and trading and examine the profitability as the reinforcement variable between CSR disclosure on stock prices and the trading volume during the COVID-19 Pandemic. The object of the study was the LQ45 companies in the Indonesia stock exchange between 2019-2020. However, the study only involved 38 companies. We used the 2019 and 2020 data accessed from the official site of the Indonesia Stock Exchange (IDX) www.idx.com. The closing stock price and trading volume data were obtained from www.yahoofinance.com. Data were tested and analyzed using Partial Least Square (PLS) technique. The study found that the disclosure of CSR was positively but not significantly influential on the stock price. The disclosure of CSR is negatively but not significantly influential on the trading volume. The profitability does not strengthen the influence of CSR disclosure on stock price, and the profitability does not strengthen the negative influence of CSR disclosure on trading volume. The research findings suggest the company management continues to run CSR programs despite the unstable economic conditions due to the COVID-19 Pandemic

The future is now: pediatric neuropsychological presurgical epilepsy evaluation in the age of COVID-19.

The objective of this brief report is to review an assessment paradigm for conducting virtual neuropsychological pre-surgical evaluations in the context of the COVID-19 pandemic. A multidisciplinary epilepsy team at a Level 4 epilepsy center within a large children's academic medical center convened to discuss the challenges and possible solutions for Phase II evaluations for pediatric patients with pharmacoresistant epilepsy during the COVID-19 pandemic. The neuropsychologists explored evidence-based methods of virtual evaluation and developed a systematic decision-making process for youth requiring a Phase II evaluation. We propose models of assessment which prioritize teleneuropsychology when possible to reduce the risk of infection: (1) evaluation with directly administered tests through a completely virtual format; (2) virtual/in-person hybrid evaluation; and (3) clinical observation/interview in a virtual format supplemented by survey data. These models are illustrated by three cases. Using virtual assessment models, the team was able to meet the urgent patient care needs and collect useful data while minimizing the risk of virus spread. The paradigms presented may be useful examples for other multidisciplinary surgical teams interested in incorporating teleneuropsychology into their practices.

Essential oil related seizures (EORS): A multi-center prospective study on essential oils and seizures in adults.

OBJECTIVE: Essential oils (EOs) like eucalyptus and camphor have pro-convulsant properties. These EOs are present in many over- the- counter balms and oils. The effect of exposure to these EOs and occurrence of seizure is not systematically studied. The aim of this study was to evaluate the relationship between essential oils and the first episode of seizure and breakthrough seizures in known epileptic patients. METHODS: This was a multi-center prospective study, conducted in four hospitals over four years. Every person presenting with the first episode of seizure or breakthrough seizure was asked about exposure to EOs, mode of exposure, time to onset of a seizure in relationship to exposure, duration of seizure, type of seizure, and antiepileptic drug therapy. RESULTS: During the four-year period there were 55 patients with essential oil-related seizure (EORS). 22(40 %) had essential oil-induced seizures (EOIS) and 33(60 %) had essential oil-provoked seizures (EOPS). The female: male ratio was 1:1.1, the age of the patients ranged from 8 months to 77 years. In the EOIS group, 95 % had generalized tonic-clonic seizures and 5% had focal impaired awareness seizures. In the EOPS group, 42.4 % had focal impaired awareness seizures, 27.3 % generalized tonic-clonic seizures, 15 % focal to bilateral tonic-clonic seizures, and 15 % focal aware motor seizures. EOs implicated were preparations containing eucalyptus and camphor. CONCLUSION: Exposure to essential oils of eucalyptus and camphor is an under-recognized cause of the first and breakthrough seizure. Identifying the true causative factor will prevent unnecessary antiepileptic drug therapy and future recurrence.

An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms (preprint)

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak's epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.

Cognitive Consequences of Social Isolation During COVID-19: side effects and treatments (preprint)

Objective: During the COVID-19 pandemic, quarantine and staying at home is advised. The social relationship between people has become deficient, and human social isolation (SI) has become the consequence of this situation. It was shown that SI has made changes in hippocampal neuroplasticity, which will lead to poor cognitive function and behavioral abnormalities. There is a connection between SI, learning, and memory impairments. In addition, anxiety-like behavior and increased aggressive mood in long-term isolation have been revealed during the COVID-19 outbreak. Methods: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2020. Results: Studies have shown that some drug administrations may positively affect or even prevent social isolation consequences in animal models. These drug treatments have included opioid drugs, anti-depressants, Antioxidants, and herbal medications. In addition to drug interventions, there are non-drug treatments that include an enriched environment, regular exercise, and music. Conclusion: This manuscript aims to review improved cognitive impairments induced by SI during COVID-19.

SIR Simulation of COVID-19 Pandemic in Malaysia: Will the Vaccination Program be Effective? (preprint)

Since the end of 2019, COVID-19 has significantly affected the lives of people around the world. Towards the end of 2020, several COVID-19 vaccine candidates with relatively high efficacy have been reported in the final phase of clinical trials. Vaccines have been considered as critical tools for opening up social and economic activities, thereby lessening the impact of this disease on the society. This paper presents a simulation of COVID-19 spread using modified Susceptible-Infected-Removed (SIR) model under vaccine intervention in several localities of Malaysia, i.e. those cities or states with high relatively COVID-19 cases such as Kuala Lumpur, Penang, Sabah, and Sarawak. The results show that at different vaccine efficacy levels (0.75, 0.85, and 0.95), the curves of active infection vary slightly, indicating that vaccines with efficacy above 0.75 would produce the herd immunity required to level the curves. In addition, disparity is significant between implementing or not implementing a vaccination program. Simulation results also show that lowering the reproduction number, R0 is necessary to keep the infection curve flat despite vaccination. This is due to the assumption that vaccination is mostly carried out gradually at the assumed fixed rate. The statement is based on our simulation results with two values of R0: 1.1 and 1.2, indicative of reduction of R0 by social distancing. The lower R0 shows a smaller peak amplitude about half the value simulated with R0=1.2. In conclusion, the simulation model suggests a two-pronged strategy to combat the COVID-19 pandemic in Malaysia: vaccination and compliance with standard operating procedure issued by the World Health Organization (e.g. social distancing).

Recovery of Olfactory and Gustatory Dysfunctions in COVID-19 Patients in Iran: A Prospective Cohort Study (preprint)

Background: Olfactory and gustatory dysfunctions (OD and GD) manifested unpredictably in COVID-19 patients. Considering the high prevalence of OD and GD and the importance of the sense of smell and taste in the quality of life, this study aimed to determine the association of some demographic and clinical factors with OD and GD recovery in COVID-19 patients in Iran.Methods: This prospective cohort study was performed on COVID-19 patients with OD and GD during the first and second peak of pandemic in Golestan province, Iran. We used a local health care registry system for data collection. All cases had positive RT-PCR test for SARS-CoV-19 in nose and nasopharynx swab samples. Variables included age, sex, ethnicity, geographical location, time of onset of symptoms, severity of OD and GD (complete or partial). The follow-up time for recovery from OD and GD was six months. Time to recovery for OD and GD was estimated by Kaplan-Meier considering complete recovery as an endpoint. Differences among groups were evaluated using log-rank test and Cox proportional-hazard models as appropriate in SPSS version 16.Results: A total of 242 patients completed the study. The mean age of patients was 39.12±11.89 years. There were 127 (52%) females. After six months, 239 (98.8%) patients had complete OD recovery and 80.9% and 83.56% of patients recovered within the first 30 days following the onset of OD or GD, respectively. The mean time of OD recovery was significantly higher (35.07±4.25 days) in cases infected in the first peak of pandemic than in the second peak (21.65±2.05 days) (p=0.004). This finding also was observed for the recovery time of GD (p=0.005). The mean recovery time of GD was significantly higher in women than men (35.55±4.33 vs. 23.20±2.46 days) (p=0.04). The age (less than 20 years), second peak of epidemic, and partial dysfunction were identified as significant predictors for recovery.Conclusions: COVID-19–related OD and GD had high rate of recovery in the first month from onset of symptoms. Age of patients, severity of OD/GD and infecting in second peak of epidemic might be related to the recovery of OD or GD in patients with COVID-19.

Recovery of Olfactory and Gustatory Dysfunctions in COVID-19 Patients in Iran: a Prospective Cohort Study (preprint)

Background: Olfactory and gustatory dysfunctions (OD and GD) manifested unpredictably in COVID-19 patients. Considering the high prevalence of OD and GD and the importance of the sense of smell and taste in the quality of life, this study aimed to determine the association of some demographic and clinical factors with OD and GD recovery in COVID-19 patients in Iran.Methods: This prospective cohort study was performed on COVID-19 patients with OD and GD during the first and second peak of pandemic in Golestan province, Iran. We used a local health care registry system for data collection. All cases had positive RT-PCR test for SARS-CoV-19 in nose and nasopharynx swab samples. Variables included age, sex, ethnicity, geographical location, time of onset of symptoms, severity of OD and GD (complete or partial). The follow-up time for recovery from OD and GD was six months. Time to recovery for OD and GD was estimated by Kaplan-Meier considering complete recovery as an endpoint. Differences among groups were evaluated using log-rank test and Cox proportional-hazard models as appropriate in SPSS version 16.Results: A total of 242 patients completed the study. The mean age of patients was 39.12±11.89 years. There were 127 (52%) females. After six months, 239 (98.8%) patients had complete OD recovery and 80.9% and 83.56% of patients recovered within the first 30 days following the onset of OD or GD, respectively. The mean time of OD recovery was significantly higher (35.07±4.25 days) in cases infected in the first peak of pandemic than in the second peak (21.65±2.05 days) (p=0.004). This finding also was observed for the recovery time of GD (p=0.005). The mean recovery time of GD was significantly higher in women than men (35.55±4.33 vs. 23.20±2.46 days) (p=0.04). The age (less than 20 years), second peak of epidemic, and partial dysfunction were identified as significant predictors for recovery.Conclusions: COVID-19–related OD and GD had high rate of recovery in the first month from onset of symptoms. Age of patients, severity of OD/GD and infecting in second peak of epidemic might be related to the recovery of OD or GD in patients with COVID-19.