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Case Report: West Nile Virus (WNV) was first isolated from the West Nile district of Northern Uganda in 1937, but was first detected in the United States well over half a century later in 1999. The arthropod-borne virus has since persisted, with 2,401 cases reported to the CDC on average annually. The infection typically causes a nonspecific acute systemic febrile illness with occasional gastrointestinal and skin manifestations;however, in less than 1% of infected patients, it can cause severe and potentially fatal neuroinvasive disease, presenting as meningitis, encephalitis or acute flaccid paralysis. Immunosuppression is one of the risk factors associated with the development of neuroinvasive disease, and chemotherapy thus places patients at risk. Uterine leiomyosarcoma is a rare gynecological malignancy. Palliative chemotherapy is common in late stage disease, but may predispose patients to conditions that present as neutropenic fever, leading to a diagnostic conundrum. This is the first case report where patient with neutropenic fever was found to have West Nile neuroinvasive disease, so it is important to include West Nile disease in the differential diagnosis. Case Description: This is a case of a 45-year-old female with history of diabetes, hypothyroidism and recently diagnosed uterine leiomyosarcoma status post tumor debulking with metastasis on palliative chemotherapy with gemcitabine that presented to the Emergency Room for a fever of 103.8 degrees Fahrenheit. Given the history of advanced leiomyosarcoma, the patient was admitted for neutropenic fever with an absolute neutrophil count of 1000. During the hospitalization, the patient became acutely altered and confused. CT head without contrast and lumbar puncture were performed. Due to clinical suspicion of meningitis, she was started on broad spectrum antibiotics. Lumbar puncture revealed leukocytosis of 168 with lymphocytic predominance and elevated protein level in the cerebrospinal fluid, therefore acyclovir was started due to high suspicion of viral meningoencephalitis. An EEG showed severe diffuse encephalopathy as the patient was persistently altered. A broad workup of infectious etiology was considered including HIV, syphilis, hepatitis A, B, C, COVID-19, adenovirus, pertussis, influenza, WNV, HHV6, coccidiomycosis, aspergillus, and tuberculosis. Patient was ultimately found to have elevated IgM and IgG titers for West Nile Virus. Discussion(s): It is important to consider a broad spectrum of diagnosis in patients with metastatic carcinoma presenting with new-onset fever and acute encephalopathy. This includes working up for other causes of altered mental status including cardiac, neurologic, psychiatric, endocrine, metabolic, electrolyte, drug, and infectious etiology. While uncommon in the healthy population, WNV encephalitis should be on the radar for any patient who is immunocompromised or on immunosuppressive therapy, especially those who present with a neutropenic fever.
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Background: Oral anti-viral therapies are licensed worldwide in COVID-19 but indications and efficacy rates vary. Aims and Objectives: To evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. Method(s): We conducted a multi-centre, open-label, randomised controlled trial of oral favipiravir in patients newly hospitalised with COVID-19, in five centres worldwide. 500 participants were randomised 1:1 to receive oral favipiravir (1800 mg twice daily (BD) for one-day;800 mg BD for nine-days) plus standard care (SC), or SC alone. NCT: 04373733. Result(s): Recruitment was performed between May 2020 and May 2021, with 251 patients randomised to favipiravir and 249 to SC. There was no difference in time to recovery in all patients (HR 1 06;95% CI 0 89-1 27;n=499;p=0.52). A faster rate of recovery was observed in patients receiving favipiravir under the age of 60 years (HR 1 35;95% CI 1 06-1 72;n=247, p=0 01). A 66 % improvement in mechanical ventilation free survival was evident in patients under 60-years of age (HR 0 34;95% CI 0 13-0 85;n=247, p=0 02). A non-significant 26 % reduction in mortality was observed in patients receiving favipiravir (favipiravir: 26;SC: 34;p=0 24). No significant differences were observed in serious adverse events (SAE) between arms (favipiravir: 36 in 27 patients;SC: 33 in 27 patients). Conclusion(s): Orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation freesurvival in patients under 60-years of age, hospitalised with COVID-19. Wider evaluation of anti-viral medications and their potential treatment combinations is warranted in patients with COVID-19.
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Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. Methods: We used linked administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program – a registry capturing stroke-related data on the entire Albertan population(4.3 million) – to identify all patients hospitalized with stroke in the pre-pandemic(01/01/2016-27/02/2020) and COVID-19 pandemic(28/02/2020-30/08/2020) periods. We examined changes in stroke presentation rates and use of thrombolysis and endovascular therapy(EVT), adjusted for age, sex, comorbidities, and pre-admission care needs;and in workflow, stroke severity(National Institutes of Health Stroke Scale/NIHSS), and in-hospital outcomes. Results: We analyzed 19,531 patients with ischemic stroke pre-pandemic versus 2,255 during the pandemic. Hospitalizations/presentations dropped(weekly adjusted-incidence-rate-ratio[aIRR]:0.48,95%CI:0.46-0.50), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, proportions of presenting patients receiving thrombolysis/EVT did not decline (thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). For out-of-hospital strokes, onset-to-door times were prolonged(adjusted-coefficient:37.0-minutes, 95%CI:16.5-57.5), and EVT recipients experienced greater door-to-reperfusion delays(adjusted-coefficient:18.7-minutes,1.45-36.0). NIHSS scores and in-hospital mortality did not differ. Conclusions: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-/in-hospital treatment delays. Our data can inform public health messaging and stroke care in future pandemic waves.
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Purpose: To determine if Apadenoson or Regadenoson has a therapeutic effect in attenuating hyper-inflammation and improving survival rate in K18-hACE2mice or Syrian hamsters infected with SARS-CoV-2. Method(s): 6-8 weeks old male K18-hACE2mice were divided into Control group that received vehicle;Test group 1 that received the drug (Apadenoson or Regadenoson) 24hrs prior to challenge with SARS-CoV-2;and Test Group 2 (Drug-delay), that received the drug with a 5 hr delay post-viral infection (n=6/grp). Viral dose was 1250 PfuHong Kong/VM20001061/2020 delivered via intranasal route. Drug was delivered subcutaneously using 1007D ALZET pumps. 6 weeks old Syrian hamsters were divided into Control group that received Vehicle and Virus (n=4) and 2 test groups (n=5/group) that received Apadenoson+Virus and Regadenoson+Virus. Drugs were delivered by 2ML2 ALZET pumps (4ug/kg/hr). Hamsters were inoculated intratracheally with 750PFU SARS-CoV-2 WA1 strain prior to treatment. Mice were weighed and clinical scores recorded daily. Bronchoalveolar lavage fluid (BALF) and serum were collected along with lungs. Plethysmography was done on days 0, 2, 4 and 7. Result(s): Apadenoson administered post-infection was efficacious in decreasing weight loss, improving clinical score, and increasing the survival rate in K18-hACE2 mice, i.e. 50% survival was observed at Day 5 and at Day 7 post-infection for drug given before or after infection respectively. Apadenoson given post-infection improved the histopathology that was observed in the vehicle control group, decreased pro-inflammatory IL-6, IFN-gamma, MCCP-1, MIP-1beta, IP-10, and Rantes in serum, increased anti-inflammatory Ang1-7 levels, and decreased monocytes in BALF. 42% of mice that received Regadenoson pre-challenge survived infection compared to 6.25% in the vehicle or Drug delay (drug given post-infection) groups. Viral titers in the lungs of Regadenoson-treated mice were found decreased. Treatment also significantly decreased CD4+, CD8+T cells, eosinophils, and neutrophils in BALF. Plethysmography, in hamsters, showed significant improvement of pulmonary function parameters, Rpef and PenH, following treatment with Apadenoson given post-infection. Apadenoson cleared the virus from BALF and maintained Ang1-7 levels. Both drugs decreased plasma IFN-gamma levels. Conclusion(s): Treatment with Apadenoson attenuated inflammation, improved pulmonary function, decreased weight loss, and enhanced survival rate following infection with SARS-CoV-2 virus. The results demonstrate the translational significance of Apadenoson in the treatment of COVID-19.
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Purpose: To determine if IgM has a direct effect in preventing SARS-CoV-2 replication in Vero E6 cells, and delaying or preventing disease in infected K18- hACE2 mice. Method(s): 1) Vero E6 cells, grown to confluence in 12 well plates, were used to test the effect of IgM in reducing the number of plaque-forming units (PFU).There were 4 groups: a) 25PFU WA-1 SARS-CoV-2 was combined with 20, 5 or 0.8mug IgM in growth medium, and incubated for 1hr in a final volume of 500ul. 100mul was added to Vero E6 cells in replicate wells and incubated for 1hr;b) 100mul of 20, 5 or 0.8mug IgM was added to Vero E6 cells and incubated. Media was aspirated and the cells were then inoculated with 25PFU WA-1 and incubated for 1hr;c) Virus control - as above, but with no IgM;d) No virus or IgM. FBS growth medium containing Avicel was overlain in the wells and incubated for 48 hours. Virus replication was stopped by incubating with 10% buffered formalin. Following removal of formalin, plates were stained with Giemsa violet, dried, and photographed. 2) A COVID -19 Spike- ACE2 binding assay kit was used to determine if IgM (2ug, 4.5ug, 20ug, 45ug IgM) inhibits the interaction between the Spike-receptor binding domain (S-RBD) and Angiotensin I ConvertingEnzyme 2 (ACE2) receptor. 3) K18-hACE2 mice were divided into 3 groups based on treatment regimen;Group 1: with IgM, No virus;2: with Saline, with virus;3: with IgM, with virus. 35ug IgM was injected intraperitoneal in a single dose, 2 days prior to infection. Mice were innoculated intranasally with 1250 pfu of HK SARS-CoV-2. Result(s): 1) Exposure of 25PFU SARS-CoV-2 to IgM (at all concentrations) prior to incubation with Vero E6 cells, inhibited its replication in Vero E6 cells. When Vero E6 cells were incubated with IgM prior to infection, no plaques were seen in wells with 20ug and 5ug IgM but were observed in wells with 0.8ug IgM. Plaques were also observed in the Virus alone group, but none were seen in the 'No IgM-No virus' group. 2) 45ug IgM/100uls inhibited the binding of S-RBD to ACE2 by ~94-100%, 20ug IgM/100uls inhibited it by ~80%, and 2 or 4.5ug/100ul by ~70-75%. Control without IgM did not inhibit the S-RBD-ACE-2 binding. 3) Pretreatment with a single low dose IgM injection delayed weight loss and mortality. Conclusion(s): IgM inhibits the replication of SARS-CoV-2 in Vero cells in vitro. It also inhibits the interaction between S-RBD that is present on the viral surface and the ACE2 receptor, by binding to S-RBD. A single low dose of IgM given prechallenge delayed disease in infected mice. The discovery that IgM interferes with the formation of the S-RBD-ACE2 complex, and that a single low dose can delay disease, indicates its translational potential as a vaccine/therapeutic to prevent or treat COVID-19.
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Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. Methods: We used linked administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program - a registry capturing stroke related data on the entire Albertan population (4.3 million) - to identify all patients hospitalized with stroke in the pre-pandemic (01/01/2016-27/02/2020) and COVID-19 pandemic (28/02/ 2020-30/08/2020) periods. We examined changes in stroke presentation rates and use of thrombolysis and endovascular therapy (EVT), adjusted for age, sex, comorbidities, and preadmission care needs;and in workflow, stroke severity (National Institutes of Health Stroke Scale/NIHSS), and in-hospital outcomes. Results: We analyzed 19,531 patients with ischemic stroke pre-pandemic versus 2,255 during the pandemic. Hospitalizations/presentations dropped (weekly adjusted-incidencerate-ratio[aIRR]:0.48,95%CI:0.46-0.50), as did population-level incidence of thrombolysis (aIRR:0.49,0.44-0.56) or EVT (aIRR:0.59,0.49-0.69). However, proportions of presenting patients receiving thrombolysis/EVT did not decline (thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02, 0.75-1.38). For out-of-hospital strokes, onset-to-door times were prolonged(adjusted-coefficient:37.0-minutes, 95%CI:16.5-57.5), and EVT recipients experienced greater door-to-reperfusion delays (adjusted-coefficient:18.7-minutes,1.45-36.0). NIHSS scores and in-hospital mortality did not differ. Conclusions: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-/in-hospital treatment delays. Our data can inform public health messaging and stroke care in future pandemic waves.
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Aim. This paper aims to bring forth how the basic right of education got adversely affected due to the COVID-19 pandemic. The unplanned and immediate shift to online classes adversely affected the students' physical and mental health as several issues that the students faced were related to the lack of adequate resources. Methods. The data for this paper were collected through a self-prepared and struc-tured questionnaire, using Google forms, which was then circulated among different stakeholders of the educational institutes. The statistical analysis of the collected data was done using Microsoft Excel. Results and conclusion. According to the analysis of the survey, smartphones (75% of the total respondents) are relatively more accessible by students in compa-rison to computers or laptops (53%). And even if students had Internet connection (57%), they faced issues of low data bandwidth (39%) leading to poor quality of online interaction in classes. Another important result suggested that 57% of students lacked a quiet room or space to attend the online classes in their homes. Finally, the negative impacts of online classes on the physical and mental health of students were also analysed. Cognitive value. The findings and the analysis of this paper would thus help teachers and institutions to understand students' views and experiences of the pandemic. This understanding would help teachers to plan their teaching accordingly, bridging the digital divide, which would help students learn and grow.
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Online learning for primary and secondary students has expanded significantly in the United States during the last two decades. In addition to the sustained growth of online learning, many schools and districts used online learning to respond to the coronavirus pandemic. As school leaders and policymakers move more students into online courses, they need information about which students succeed and struggle online. We examine the relationship between student traits and academic success in a statewide online learning program. We find that students identified with specific exceptionalities, students who identify as male, students from disadvantaged socioeconomic backgrounds, and students from cities or fringe rural areas were more likely to struggle in their online courses. This information comes at a vital time as school leaders seek to determine the effects of widespread online learning, make decisions about the support students will need after the pandemic ends, and develop the best online learning approaches when in-person schooling returns.