Audiometry-Confirmed Sudden Sensorineural Hearing Loss Incidence among COVID-19 Patients and BNT162b2 Vaccine Recipients.

OBJECTIVE: To compare sudden sensorineural hearing loss (SSNHL) incidence rates over the coronavirus disease 2019 (COVID-19) outbreak and the COVID-19 vaccination campaign periods to pre-COVID-19 periods. STUDY DESIGN: Retrospective cohort. SETTING: Secondary hospital. PATIENTS: Patients >12 years with auditory-confirmed SSNHL were enrolled. COVID-19 status and BNT162 inoculation records ≤28 days before SSNHL diagnosis were retrieved. Patients were categorized according to their date of presentation over four equal periods: 1) July 2018-April 2019 (first prepandemic period), 2) May 2019-February 2020 (second prepandemic period), 3) March 2020-December 2020 (COVID-19 outbreak), and 4) January 2021-October 2021 (BNT162b2 vaccinations campaign). INTERVENTIONS: Pre- and post-COVID-19 emergence; BNT162b2 vaccine. MAIN OUTCOME MEASURES: Incidence rate ratios (IRRs) were calculated to compare SSNHL cases during the COVID-19 and vaccination periods with pre-COVID-19 periods. RESULTS: Of the 100 patients with SSNHL over the four periods, 1 had COVID-19 and 8 were vaccinated. The annual SSNHL incidence was 12.87, 12.28, 13.45, and 19.89 per 100,000 over periods 1 to 4, respectively. SSNHL incidence over the third period was not significantly different than the first/second periods (IRR = 1.045, 95% confidence interval [CI] = 0.629-1.85, ρ = 0.788, and IRR = 1.095, 95% CI = 0.651-1.936, ρ = 0.683, respectively), whereas SSNHL incidence rate over the fourth period was higher (IRR = 1.545, 95% CI = 0.967-2.607, ρ = 0.068, and IRR = 1.619, 95% CI = 1-2.73, ρ = 0.05, respectively). SSNHL incidence in vaccine recipients was lower than prepandemic unvaccinated patients (IRR = 0.584, 95% CI =0.464-1.67, ρ = 0.984, and IRR = 0.612, 95% CI =0.48-1.744, ρ = 0.92, respectively). CONCLUSION: There were fewer SSNHL cases during the first COVID-19 months. Although the SSNHL rate over the COVID-19 vaccination campaign increased, it was not higher for patients who received the BNT162b2 vaccine.

Trends in Pediatric Acute Otitis Media Burden During the First COVID-19 Year.

OBJECTIVE: To study the changes in acute otitis media (AOM) pediatric emergency department (PED) visits and pediatric admission before and during the first coronavirus disease 2019 (COVID-19) year. STUDY DESIGN: Retrospective case review. SETTING: Secondary care center. PATIENTS: Children younger than 18 years with all-cause and AOM-related PED visits and pediatric admissions for 3 years (March 1, 2018-January 28, 2021) were identified. Children were categorized according to age (0-2, 2-6, and 6-18 yr) and their date of presentation: pre-COVID-19 (yearly average of visits/admissions during the 2 prepandemic years: March 1, 2018-February 28, 2019 and March 1, 2019-February 29, 2020) or COVID-19 year (visits/admissions between March 1, 2020-February 28, 2021). INTERVENTION: Pre- and post-COVID-19 emergence, alternating lockdowns, kindergarten and school closures, and increased hygiene measures. MAIN OUTCOME MEASURE: Post- versus pre-COVID-19 AOM PED visit and pediatric admission incidence rate ratios (IRRs), using a generalized estimating equation model with a negative binomial regression calculation, while controlling for monthly fluctuations. RESULTS: Annual AOM visits/admissions during the pre-COVID-19 and COVID-19 years were 517 and 192 and 256 and 94, respectively (p < 0.05 for both). For children aged 0 to 2 years, AOM visits/admissions significantly decreased during the first COVID-19 year, compared with the pre-COVID years (ß = -1.11 [IRR, 0.33; 95% confidence interval [CI], 0.26-0.42; p < 0.005] and ß = -1.12 [IRR, 0.33; 95% CI, 0.25-0.42; p < 0.005]). Relatively to all-cause of children aged 0 to 2 years, AOM visits/admissions decreased during the first COVID-19 year versus the pre-COVID-19 years (ß = -2.14 [IRR, 0.12; 95% CI, 0.08-0.17; p < 0.005] and ß = -1.36 [IRR, 0.26; 95% CI, 0.23-0.29; p < 0.005]) and had monthly fluctuations coinciding with the lockdown/relaxation measures. For children aged 2 to 6 years, the reduction in AOM admissions was significant (ß = -1.70, IRR, 0.18; 95% CI, 0.09-0.37; p < 0.005). No significant differences were observed for children aged 6 to 18 years because of the small sample size. CONCLUSION: Pediatric AOM burden substantially decreased during the first COVID-19 year.

Otitis Media Practice During the COVID-19 Pandemic.

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen responsible for the eruption of the COVID-19 global pandemic. Following the pandemic declaration in many countries and by the World Health Organization in March 2020, preventive proactive measures were imposed to limit COVID-19. These included social distancing; lockdowns; closure of workplaces; kindergartens and schools; increased hygiene; use of antiseptics and alcohol-based gels; frequent temperature measurements and wearing masks. These measures were not the only ones taken, as hospitals and clinics tried to minimize treating non-urgent medical referrals such as OM, and elective surgical procedures were canceled, such as ventilating tube insertion (VTI). These changes and regulations altered the way OM is practiced during the COVID-19 pandemic. Advents in technology allowed a vast use of telemedicine technologies for OM, however, the accuracy of AOM diagnosis in those encounters was in doubt, and antibiotic prescription rates were still reported to be high. There was an overall decrease in AOM episodes and admissions rates and with high spontaneous resolution rates of MEF in children, and a reduction in VTI surgeries. Despite an initial fear regarding viral shedding during myringotomy, the procedure was shown to be safe. Special draping techniques for otologic surgery were suggested. Other aspects of OM practice included the presentation of adult patients with AOM who tested positive for SARS-2-CoV and its detection in MEF samples in living patients and in the mucosa of the middle ear and mastoid in post-mortem specimens.

Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo.

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1ß, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option.

Report of National Brain Tumor Society roundtable workshop on innovating brain tumor clinical trials: building on lessons learned from COVID-19 experience.

On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.