SPRINTER: A Randomized, Double-Blind, Placebo Controlled, Phase 3 Trial to Determine the Efficacy and Safety of Inhaled Interferon Beta-1a (SNG001)for the Treatment of Patients Hospitalised Due to COVID-19 (NCT04732949)

Rationale: Interferon beta (IFN-beta) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-beta-1a nebuliser solution) aims to restore lung IFN-beta levels. Method(s): Adults hospitalised due to COVID-19 requiring low flow oxygen were randomized to receive SNG001 (314) or placebo (309) OD for 14 days, plus standard-of-care. Efficacy was assessed by change in clinical condition using the WHO 9-point Ordinal Scale for Clinical Improvement (OSCI). Primary endpoints: time to discharge (OSCI <=2) and time to recovery (OSCI <=1). Key secondary endpoints: progression to severe disease or death (OSCI >=5), progression to intubation or death (OSCI >=6), and death. Result(s): Most patients were discharged rapidly from hospital and there was no effect of SNG001 on time to discharge or recovery. However, there was an encouraging signal for prevention of progression to severe disease or death (ITT 26% relative risk reduction (RRR);Odds Ratio (95% CI): 0.71 (0.44, 1.15);Per Protocol 36% RRR;OR 0.63 (0.35, 1.13)). Post hoc analyses supported this observation with enhanced effects favouring SNG001 in subgroups at higher risk of progression (>=65 years;>=1 comorbidity;oxygen saturation <=92% and/or respiratory rate >=21 breaths/min on oxygen). Conclusion(s): If the encouraging signal in the relative risk of disease progression or death (~30% reduction) observed in this 300 patient/arm trial were confirmed in a larger trial, SNG001 could become a useful treatment option for hospitalised COVID-19 patients.

WHAT HAPPENED TO THE K–12 EDUCATION LABOR MARKET DURING COVID? THE ACUTE NEED FOR BETTER DATA SYSTEMS

The COVID-19 pandemic upended the U.S. education system in ways that dramatically affected the jobs of K–12 employees. How-ever, there remains considerable uncertainty about the nature and degree of staffing challenges during the pandemic. We draw on data from the Bureau of Labor Statistics (BLS) and State Education Agencies (SEA) to describe patterns in K–12 education employment and to highlight the limitations of available data. Data from the BLS suggest overall employment in the K–12 labor market de-clined by 9 percent at the onset of the pandemic and remained well below pre-pandemic levels more than two years later. SEA data suggest that teachers did not leave the profession en masse as many predicted, with turnover decreasing in the summer of 2020 and then increasing modestly in 2021 back to pre-pandemic levels. We explore possible explanations for these patterns including weak hiring through the summer of 2020 and high attrition among K–12 instructional support and noninstructional staff. State vacancy data also suggest that schools faced substantial challenges filling open positions during the 2021–22 academic year. Our analyses illustrate the imperative to build nationally rep-resentative, detailed, and timely data systems on the K–12 education labor market to better inform policy. © 2022 Association for Education Finance and Policy.

Advocating for global health locally: Swedish Red Cross nurses as nursing activists for COVID-19 vaccination

The COVID-19 vaccination has created turbulence in many communities. The dilemma has been particularly alive among health professionals such as nurses. As lecturers at the Swedish Red Cross University, whose academic profile is global nursing and global health, we promote the importance of the nursing profession as advocates for the COVID-19 vaccination. The main objective of this commentary is to reflect on the Red Cross Red Crescent (RCRC) fundamental tenet based on its principles in relation to nursing commitment beyond traditional responsibilities in times of pandemic when urgency, reactivity, and pedagogical health education become a priority. The notion of ‘globality’ and the contextualization and modernization of nursing responsibilities are associated with these professional reflections. We conclude that activism and advocacy, on issues crucial to planetary health and the advancement of social justice globally, are the responsibility of nurses. Furthermore, the liability of RCRC nurses is accentuated by the seven principles and the significance of humanity within the global perspective. © The Author(s) 2022.

The COVID-19 viral 3a protein forms a potassium channel that can be inhibited by antiarrhythmic drugs

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Deutsche Gesellschaft für Kardiologie /German Cardiac Society Joachim Herz Stiftung /Joachim Herz Foundation Background/Introduction Supraventricular and ventricular arrhythmias can often be observed in patients with COVID-19 infection. Both, the clinically observed increase in cardiac biomarkers as well as histological studies indicate virus replication within cardiomyocytes. The 3a open reading frame of the viral genome encodes for a transmembrane protein that is transported to the cell membrane where it can serve as a potassium channel. Purpose The aim of this study was to investigate whether COVID-19 infected induced pluripotent stem cell (iPSC)-derived cardiomyocytes also express the 3a protein and whether the potassium currents that are conducted through the 3a protein can be inhibited by clinically used antiarrhythmic drugs. Methods and Results iPSC-derived cardiomyocytes were infected with COVID-19 and subsequently subjected to immunoblotting, where expression of the 3a protein could be observed. Plasmid DNA, encoding the COVID-19 3a protein, was generated by gene synthesis and used for in vitro transcription of cRNA. 3–5 days after intracytoplasmic injection of the 3a protein cRNA into Xenopus laevis oocytes, potassium currents could be measured by two-electrode voltage clamp recordings. While class I and class IV antiarrhythmic drugs showed only minor effects on the potassium currents of the 3a protein, a robust inhibition by several beta-blockers and by class III antiarrhythmic drugs could be observed. The strongest effects were found with dofetilide (58.1 % inhibition at 100 µM) and amiodarone (50.1 % inhibition at 100 µM, IC50 level 4.7 µM). An in silico docking analysis, based on the recently revealed crystal structure of the 3a protein, identified the amino acid residues K61 and D142 as part of the binding site of amiodarone. After deactivation of these amino acid residues by site-directed mutagenesis, the inhibition by amiodarone was significantly attenuated. Conclusion The COVID-19 viral 3a protein is expressed in COVID-19-infected iPS-derived cardiomyocytes and forms a potassium channel that can be inhibited by antiarrhythmic drugs.

Impact of COVID-19 pandemic and total neoadjuvant therapy (TNT) implementation in pathological complete response (pCR) rates in patients (pts) with locally advanced rectal cancer (LARC)

Background: Strategies for locally advanced rectal cancer LARC usually consisted of neoadjuvant concomitant chemoradiotherapy (CRT) followed by adjuvant chemotherapy, or short-course radiotherapy (SCRT). TNT is a novel approach for LARC, with several randomized clinical trials exploring its role and paving the way for implementation in clinical practice. Nevertheless, the COVID-19 pandemic represented a challenge for a timely diagnosis, implementation and follow-up of new treatment strategies in these pts. Methods: Records of all the pts diagnosed with LARC and stage IV rectal cancer evaluated in the Oncology department of Vall d’Hebron Hospital between Jan 1st, 2017 and Dec 31th 2021 were included. The period 2017-19 was considered pre-pandemic (PP) and 2020-2021 during-pandemic (DP). Patients with LARC receiving neoadjuvant and/or adjuvant treatment were analyzed, including those treated with SCRT, CRT, and TNT. Data regarding demographics, diagnosis and staging, preoperative treatment received, surgical outcomes, including treatment response, and pathological stage were collected. Results: 390 patients were included (31.28% female, 68.71% Male, median age 69). LARC pts characteristics included 123 (31.54%) either cT4 or cN2, 59 low rectal cancers, 4 with signet ring cells. Neoadjuvant treatment was done in 160 pts (CRT) and 59 pts (TNT). pCR was achieved in 20% and 22% for CRT, and TNT respectively (p0.84). 32 pts received only SCRT with 6.25% pCR. An increased ratio of stage IV pts compared to LARC was evident during the pandemic (stage IV 26.38% 2017-2019, 37.14% 2020-2021, p=0.044). The proportion of high risk LARC increased during pandemic (34.89% PP vs 39.04% DP, p=0.041). No difference was found in terms of pCR amongst the PP and DP patients (25.3% vs 27%, p=0.83) nor different strategies (TNT: 26.47% PP and 26.6% PD, p=0.98 and CRT 23.89% PP and 27.27 % PD, p=0.82). Conclusions: Efficacy of LARC neoadjuvant treatment measured by pCR was maintained in pts before and during COVID-19 pandemic despite an increasing proportion of new LARC high-risk pts. Evaluation of TNT impact in LARC outcomes was challenging because of pandemic confounding role. Real-world data in a post-pandemic setting is essential to evaluate outcome trends in LARC pts;an increase in high-risk LARC and metastatic pts should be expected. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosures: A. García Álvarez: Speaker Bureau / Expert testimony: ANGELINI PHARMA ESPAÑA;Travel / Accommodation / Expenses: Pfizer, Ipsen, Eisai Europe. All other authors have declared no conflicts of interest.

Comparison of Video-Coached Remote Spirometry with In-Person Spirometry in Patients with Severe Asthma Participating in the NHLBI PrecISE Network

Introduction: PrecISE is an ongoing Phase II clinical trial sponsored by the National Heart, Lung, and Blood Institute to investigate the efficacy of several treatments for severe asthma. The threat of COVID-19 has raised interest in obtaining reliable spirometry data for asthma research and clinical care in a remote, “no-touch” fashion. Prior studies of the accuracy of remote spirometry have not included real-time coaching. The PrecISE investigators hypothesized that remote spirometry with real-time video coaching could provide an accurate FEV1 for use as a study endpoint in a clinical trial setting. Methods: PrecISE network participants had remote spirometry post-bronchodilator (4 puffs of albuterol) measured with video coaching from trained research coordinators using the ZEPHYRx platform connected to MIR Spirobank Smart handheld spirometers. Remote spirometry measurements occurred within a +/- 3-day window from scheduled in-person PrecISE visits during which in-person spirometry with bronchodilator challenge was measured with standard equipment (Vyaire Medical). All measurements occurred during the screening/run-in period of the PrecISE protocol. Both remote and in-person spirometry was overread by the PrecISE Spirometry Core and only included in analysis if sessions met ATS acceptability and reproducibility criteria. Correlations between remote and in-person FEV1 and FVC were analyzed, and Bland-Altman plots generated. As a comparison, within subject biological variability was measured using data from separate in-person visits during the screening/run-in period. Results: A total of 128 pairs of remote/in-person spirometry data were obtained. The mean FEV1 for remote spirometry was 2.50 L (SD 0.81) and for inperson spirometry was 2.42 L (SD 0.80), with an estimated correlation of 0.95 (95% CI: 0.93, 0.97). The mean difference in FEV1 (in-person - remote) was -0.07 L (95% CI: -0.11, -0.03, SD 0.25). The mean FVC for remote spirometry was 3.72 L (SD 1.01) and for in-person spirometry was 3.53 L (SD 0.93), with an estimated correlation of 0.91 (95% CI: 0.87, 0.93). The mean difference in FVC (in-person - remote) was -0.19 L (95% CI: -0.27, -0.12, SD 0.42). A total of 142 pairs of repeated in-person spirometry measurements were performed (median time between measurements: 43 days), with mean difference in FEV1 of -0.01 L (95% CI: -0.06, 0.03) and FVC of -0.02 L (95% CI: -0.07, 0.03). Bland-Altman plots for FEV1 differences are shown in Figure 1. Conclusions: Remote spirometry with real-time video coaching provides a reliable FEV1 measurement which correlates closely with in-person spirometry and is suitable for use in clinical trials. (Figure Presented).

SPRINTER: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Determine the Efficacy and Safety of Inhaled Interferon Beta-1a (SNG001) for the Treatment of Patients Hospitalized Due to COVID-19 (NCT04732949)

Rationale: New effective treatments are urgently needed for patients hospitalized with COVID-19, due to lower respiratory tract illness caused by the SARS-CoV-2 virus. SARS-CoV-2 suppresses production of interferon-beta (IFN-β), a naturally occurring protein and key driver of innate antiviral immunity, to evade host immune responses. Patients with severe disease have reduced ability to generate a primary interferon response in the lungs because of genetic, comorbid and/or autoantibody host responses. In vitro, IFN-β has potent antiviral activity against SARS-CoV-2, including known variants of concern. SNG001 is an IFN-β-1a nebulizer solution administered directly into the lungs to boost IFN-β levels at the site of infection. In trials of patients with chronic respiratory diseases and viral infections, SNG001 was well tolerated and improved lung function, providing the rationale to treat patients with COVID-19, at risk of progressing to severe disease. In a phase 2 trial, non-ventilated hospitalized patients with COVID-19 receiving SNG001 were more than twice as likely to recover to “no limitation of activities” and experienced significantly reduced breathlessness over the treatment period versus those receiving placebo. These encouraging results with inhaled IFN-β supported progression of SNG001 into a phase 3 trial in patients hospitalized due to COVID-19 (SPRINTER). Methods: Adults (≥18 years) hospitalized with COVID-19, requiring supplemental oxygen via nasal prongs or mask were randomized to receive SNG001 or placebo (1:1) by inhalation once daily for 14 days, in addition to standard-of-care treatment. Efficacy was assessed in the intention-to-treat population by change in clinical condition using the WHO 9-point Ordinal Scale for Clinical Improvement (OSCI;Table). Primary endpoints: time to hospital discharge (OSCI ≤2) and time to recovery to “no limitation of activities” (OSCI ≤1). Key secondary endpoints: progression to severe disease or death (OSCI ≥5), progression to intubation or death (OSCI ≥6), and death. Cox proportional hazards modeling was used to evaluate primary endpoints. Key secondary endpoints were analyzed using logistic regression. Results: Between January and November 2021, 623 patients were randomized to treatment. Preliminary, blinded data show that median duration of symptoms was 9 days;22% (135/623) of patients were partially/fully vaccinated;median duration of hospital stay was 7 days;84% (525/623) of patients were discharged by Day 35;13% (80/623) progressed to severe disease or died within 35 days;and 5% (31/623) died within 35 days. Conclusions: Recruitment into the SPRINTER trial was completed in November 2021. Unblinded efficacy and safety results (expected Q1 2022) will be presented. (Table Presented).

The OM-85 Bacterial Lysate Inhibits SARS-CoV-2 Infection of Epithelial Cells by Downregulating SARS-CoV-2 Receptor Expression

RATIONALE: Treatments for the coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through the interactions of its spike (S) protein with ACE2 and TMPRSS2 on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. Our finding that the airway administration of OM-85 inhibits Ace2 and Tmprss2 transcription in mouse lungs prompted us to investigate whether and how OM-85 may protect non-human primate and human epithelial cells against SARS-CoV-2 infection. METHODS: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2- transfected HEK293T cells treated with OM-85 in vitro. RESULTS: OM-85 significantly downregulated ACE2 and TMPRSS2 mRNA in epithelial cell lines and primary bronchial epithelial cells, and strongly inhibited SARS-CoV-2 S protein binding to, SARS-CoV-2 S proteinpseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on the downregulation of SARS-CoV-2 receptor expression. CONCLUSIONS: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of COVID-19.

Development and Evaluation of Bluetooth Low-Energy Device for Electronic Encounter Metrics

The coronavirus disease 2019 (COVID-19) pandemic led to the need for tracking of physical contacts and potential exposure to disease. Traditional contact tracing can be augmented by electronic tools called "electronic contact tracing" or "exposure notification.". Some methods were built to work with smartphones;however, smartphones are not prevalent in some high-contact areas (e.g., schools and nursing homes). We present the design and initial testing of low-cost, highly privacy preserving wearable exposure notification devices. Several devices were constructed based on existing hardware and operated independently of a smartphone. The method (devices and analyses) was not able to reliably use the received signal strength indicator (RSSI) as a proxy for distance between pairs of devices;the accuracy of RSSI as a proxy for distance decreased dramatically outside of the idealized conditions. However, even an imperfect device could be useful for research on how people use and move through spaces. With some improvement, these devices could be used to understand disease spread and human or animal interaction in indoor environments.

A Blueprint for Scaling Tutoring and Mentoring Across Public Schools

In this thought experiment, we explore how to make access to individualized instruction and academic mentoring more equitable by taking tutoring to scale as a permanent feature of the U.S. public education system. We first synthesize the tutoring and mentoring literature and characterize the landscape of existing tutoring programs. We then outline a blueprint for integrating federally funded and locally delivered tutoring into the school day. High school students would serve as tutors/mentors in elementary schools via an elective class, college students in middle schools via federal work-study, and 2- and 4-year college graduates in high schools via AmeriCorps. We envision an incremental, demand-driven expansion process with priority given to high-needs schools. Our blueprint highlights a range of design tradeoffs, implementation challenges, and program costs. We estimate that targeted approaches to scaling school-wide tutoring nationally, such as focusing on K–8 Title I schools, would cost between $5 and $16 billion annually. © The Author(s) 2021.

Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.

BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.

Interferons and potential consequences for sars-cov-2 infection

RATIONALE: Severe acute respiratory syndrome 2 (SARS-CoV-2) and resulting coronavirus disease 2019 (COVID-19) have been associated with several symptoms including fever, chills, cough, fatigue, loss of taste or smell, sore throat, and congestion. Moderate cases may require hospitalization and severe cases have resulted in death. Interferons (IFNs) are a class of immune molecules typically involved in the anti-viral response. Their role in SARS-CoV-2 infection is controversial as IFNs may increase angiotensin-converting enzyme 2 (ACE2) expression, the receptor for SARS-CoV-2, yet also enhance viral clearance. IFN-α2 stimulation increases gene expression of Interleukin-6 (IL-6), a cytokine that activates STAT proteins and is associated with poor hospital outcomes in COVID-19 patients. Meanwhile, surfactant protein A (SP-A), an immunomodulatory respiratory protein, is known from our work to bind to cytokine receptors such as IL-13α1 and IL-13 ligand (Francisco et al, JI 2020). Therefore, we hypothesized that SP-A binds to ACE2 and IL-6, making it a possible novel regulator of SARS-CoV-2 infection that potentially impacts disease severity.Methods: Normal human bronchial epithelial cells (NHBE) and asthmatic diseased bronchial human epithelial cells (DHBE) were cultured at air liquid interface for 2 weeks and stimulated with increasing doses of IFN-α2 (0.1, 1, and 10 ng/ml) for 48 hours. RT-PCR was performed and gene expression for ACE2 and IL-6 was assessed by normalizing to PPIA. Binding assays were performed using a 96-well, immunosorbent assay coated with either IL-6, IL-6Rα, GP130, ACE2, IFN-α2 or the negative control, EGFR and incubated with increasing concentrations of full-length SP-A (0-5000 ng/ml) and a SPA-HRP conjugated antibody. In separate experiments, western blotting was used to detect levels of total and phosphorylated STAT-1 in primary asthmatic bronchial epithelial cells treated for 30 minutes with IL-6 (10 ng/ml) in the presence and absence of SP-A2 (20 ug/ml) peptide.Results: Stimulation with 10 ng/ml IFN-α2 significantly increased ACE2 and IL-6 gene expression in NHBE and DHBE cells (p<.05). Full length SP-A was found to bind ACE2, both IL-6 receptors (IL-6Rα and GP-130), and to a lesser extent, IL-6 cytokine. SP-A did not bind to IFN-α2 or EGFR. Asthmatic primary human lung epithelial cells treated with IL-6 resulted in phosphorylation of STAT-1, and pre-treatment with SP-A2 peptides reduced this activation by approximately 45%.Conclusion: While IFNs may play a role in viral clearance, our data suggest potential dysregulation of mechanisms affecting the response to SARS-CoV-2. SP-A may be protective based upon its effects on ACE2 and IL-6.

Type 2 inflammation reduces ACE2 protein in bronchial and nasal epithelial cells

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with several chronic lung-based comorbidities that have been shown to increase severity and mortality, with the notable exception of asthma. Our group has published that bronchial epithelial cells from atopic normal and asthmatic patients and treated with Interleukin-13 (IL-13), a type 2 cytokine, suppressed gene expression of angiotensinconverting enzyme 2 (ACE2), a key receptor for SARS-CoV-2 (Kimura H, et al. 2020). To further complement our studies, we examined ACE2 gene expression from individuals with severe asthma, and also assessed ACE2 protein levels from all groups. Because ACE2 is expressed in nasal epithelium, we also examined the effects of IL-13 on ACE2 expression in nasal epithelial cells. Objective: To determine if ACE2 gene and protein expression in upper and lower airways is modulated by IL-13. Methods: Non-atopic and atopic non-asthmatic normal, nonsevere and severe asthmatic participants were recruited and underwent bronchoscopy and nasal brushings to obtain primary bronchial and nasal epithelial cells. Epithelial cells were cultured at ALI for 2 weeks. Cells were treated with IL-13 (10 ng/ml) for 48 hours for gene expression and at 10, 50 and 100 ng/ml for 72 hours to determine protein expression from cell lysates by ELISA. Results: In bronchial epithelial cells, gene expression of ACE2 decreased following IL-13 treatment compared to untreated control: mean reduction: 0.52 ± 0.12 (p<.001) in atopic normal cells, 0.67 ± 0.14 (p=0.038) in non-severe asthma cells, and 0.66 ± 0.03 (p<.001) in severe asthma cells. There was no significant difference in the reduction in ACE2 gene expression between these three groups following IL-13 treatment. In nasal epithelial cells, the mean reduction in ACE2 gene expression was 0.42 ± 0.08 (p<.001) in atopic normal cells and 0.48 ± 0.01 (p<.001) in non-severe asthma cells) compared to untreated control. IL-13 significantly decreased ACE2 protein levels in bronchial epithelial cells in a dose dependent and similar manner in all groups compared to untreated control (p=0.011 in non-atopic normal, p=0.023 in atopic normal, p=0.016 in non-severe asthma, and p=0.011 in severe asthma, respectively, by Jonckheere-Terpstra test). IL-13 also reduced ACE2 protein expression in atopic normal and non-severe asthma group (p=0.033 and 0.003, respectively) in nasal epithelial cells. Conclusion: IL-13 attenuates ACE2 gene expression and protein production in both nasal and bronchial epithelial cells regardless of asthma and atopic status. These observations suggest that type 2 cytokines may confer protection in SARS-CoV-2 infection.

Anaphylaxis to vaccination and polyethylene glycol (PEG): A perspective from the European Anaphylaxis Registry

The Covid-19 pandemic is currently one of the most important health challenges, and the recently approved vaccines can save millions of lives. However, the fact that anaphylaxis might occur after vaccination has raised much concern. Currently, Centers for Disease Control and Prevention (CDC) reported the rate of 2.5 - 4.7 cases/million mRNA vaccine doses administered.