Ruptured abdominal aortic aneurysms are associated with high mortality rates and require prompt diagnosis with subsequent intervention. CT scan is considered the gold-standard for diagnosis, however, in the acute setting ultrasound may be a reasonable diagnostic test for certain patients. We report a case that demonstrates the utility of bedside ultrasound of rAAA for a patient in extremis. Also, we provide a brief review of literature for the diagnosis of rAAA with ultrasound.

This spring, instructors moved their courses online in an emergency fashion as campuses were closed due to the pandemic. As colleges prepare for the next academic year, there is a need to provide flexible instruction that is more intentional for quality online learning. We taught two undergraduate courses online for the first time this spring and surveyed our students’ reactions to the course experiences. From our experiences and student feedback we identified design elements and activities that were beneficial in promoting student engagement, sense of connectivity, and learning. We describe four qualities for a successful transition to online learning: 1) big questions and core concepts; 2) peer groups including reflective writing; 3) outreach to broader scientific community; and 4) instructor’s social presence in the class. Our experience gives us confidence that courses can be redesigned for online without compromising rigor or essential learning goals.

Introduction: Although prolonged respiratory symptoms following SARS-CoV-2 infection have been reported in adults, there is a paucity of literature describing post-acute symptoms in pediatric patients following COVID-19. In this study we describe health data and respiratory findings in pediatric patients presenting with complaints of persistent respiratory symptoms following acute COVID-19 infection. Methods: This study included patients referred to Pulmonary Clinic at the Children’s Hospital of Philadelphia between December 2020 and April 2021 (n=29). Inclusion criteria included a history of SARS-CoV-2 RNA positivity or confirmed close household contact. A retrospective chart review was performed and demographic, clinical, imaging, and functional test data were collected. Results: The mean age at presentation to clinic was 13.1 years (range: 4-19 years). Patients had persistent respiratory symptoms ranging from 1.3 to 6.7 months post-acute infection. Persistent dyspnea and/or exertional dyspnea were present in nearly all (96.6%) of the patients at the time of clinic presentation. Other reported chronic symptoms included cough (51.7%) and exercise intolerance (48.3%). Fatigue was reported in 13.7% of subjects. Many subjects were overweight or obese (62.1%) and eleven subjects had a prior history of asthma. Lung function was normal in most patients. The six-minute walk test (6MWT) revealed exercise intolerance and significant tachycardia in two-thirds of children tested. Conclusion: Exertional dyspnea, cough and exercise intolerance were the most common respiratory symptoms in children with post-acute COVID-19 respiratory symptoms seen in an outpatient pulmonary clinic. Lung function, however, was mostly normal, and exertional intolerance was frequently demonstrated using the 6MWT.

Background Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high risk infants at 12 months. Methods This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months. Results 321 infants were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, P>0.05). Conclusions This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants.

Changing and moving toward online shopping has made it necessary to customize customers' needs and provide them more selective options. The buyers search the products' features before deciding to purchase items. The recommender systems facilitate the searching task for customers via narrowing down the search space within the specific products that align the customer needs. Clustering, as a typical machine learning approach, is applied in recommender systems. As an information filtering method, a recommender system clusters user's data to indicate the required factors for more accurate predictions by calculating the similarity between members of a cluster. In this study, using the Gaussian mixture model clustering and considering the scores distance and the value of scores in the Pearson correlation coefficient, a new method is introduced for predicting scores in machine learning recommender systems. To study the proposed method's performance, a Movie Lens data set is evaluated, and the results are compared to some other recommender systems, including the Pearson correlation coefficients similarity criteria, K-means, and fuzzy C-means algorithms. The simulation results indicate that our method has less error than others by increasing the number of neighbors. The results also illustrate that when the number of users increases, the proposed method's accuracy will increase. The reason is that the Gaussian mixture clustering chooses similar users and considers the scores distance in choosing similar neighbors to the active user.

To contain transmission of COVID-19, lockdown or strict restriction of people’s mobility outside their residence was imposed worldwide. In Nepal, the first phase of nationwide lockdown was observed from March 24 to July 21, 2020. This sudden halt in human activities brought positive and negative impacts on forests and wildlife. We undertook a study was undertaken to know the impact of the CoViD-19 lockdown on wildlife and forests in the protected areas (PAs) of Nepal. The study was carried in July and September 2020, data of illegal activities recorded by the PAs and also those reported by media were obtained and analyzed. Key Informant Interview (KII) was done with the park officers and security personnel by virtual communication that included telephone, messenger app, and ZOOM video meeting to collect detailed information and for verification. The collected data were categorized into four groups: i) wildlife killed, ii) wildlife injured, iii) arrest incidents related to forest crime, and iv) arrest incidents related to wildlife crime. Data from the fiscal year 2019-2020 were analyzed, comparing before lockdown and after. The study found trends of substantial increases in. wildlife death in two PAs, Banke National Park and Bardia National Park out of 20 during the lockdown. Similarly, Chitwan National Park (CNP) and Shivapuri Nagarjun National Park (SNNP) witnessed a rise in wildlife poaching. CNP and SNNP are located close to highly populated cities and also having human settlements in their peripheries. Interestingly, wildlife was easily sighted inside PAs during the lockdown, presumably because the absence of visitors and human activities during the lockdown decreased disturbance. Thus, a paradoxical situation was observed with the wildlife enjoying the freedom of movement on the one hand, but with poachers, many of them laid off from other activities, taking advantage of the lapse in security.

Reconstructing ecological niche evolution can provide insight into the biogeography and diversification of evolving lineages. However, comparative phylogenetic methods can infer the history of ecological niche evolution inaccurately because (1) species’ niches are often poorly characterized; and (2) phylogenetic comparative methods rely on niche summary statistics rather than full estimates of species’ environmental tolerances. Here we propose a new framework for coding ecological niches and reconstructing their evolution that explicitly acknowledges and incorporates the uncertainty introduced by incomplete niche characterization. Then, we modify existing ancestral state inference methods to leverage full estimates of environmental tolerances. We provide a worked empirical example of our method, investigating ecological niche evolution in the New World orioles (Aves: Passeriformes: Icterus spp.). Temperature and precipitation tolerances were generally broad and conserved among orioles, with niche reduction and specialization limited to a few terminal branches. Tools for performing these reconstructions are available in a new R package called nichevol.

Spatial and temporal heterogeneity, or messiness, is a broadly desirable characteristic of river corridors and an indicator of many of the geomorphic processes that sustain fluvial ecosystems. However, quantifying geomorphic heterogeneity is complicated by a lack of consistent metrics, classification schemas for dividing the river corridor into the patches that form the basis for those metrics, and guidance on interpreting metrics. Drawing from both geomorphic and landscape ecology concepts, we offer ideas and guidance intended to help investigators, from researchers to restoration practitioners, more effectively and reliably use heterogeneity to describe river corridor processes and characteristics. We define geomorphic heterogeneity both spatially and temporally. Spatially, heterogeneity can be described by diversity, or the evenness and richness of geomorphic units, and spatial configuration, or the arrangement and shape of geomorphic units. Temporally, heterogeneity can be described by turnover rate, or the rate of change of geomorphic units. Interpretation of heterogeneity metrics depends integrally on the definition of the geomorphic unit schema on which metrics are based. Contextual information, such as measurements of process space (i.e., how much room a river has to move), disturbance frequency, and geomorphic trajectory, can also be key to interpreting measurements of heterogeneity. Geomorphic applications of heterogeneity require carefully defined geomorphic unit schemas that reflect processes and characteristics of interest, robust metrics of heterogeneity whose meaning is appropriate to the question at hand, and interpretation of those metrics based on the context of expected geomorphic processes and the disturbance regime.

Background and Purpose: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry or physiology, lacks a consensus list of such core concepts. Experimental approach: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents. Key Results: The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology. Conclusion and Implications: This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists’ readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges.Objective This study aims to examine community pharmacists’ views on their work environment, policies, and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic.Setting An online survey of pharmacists practicing in community pharmacy setting in Malaysia.Method A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilizing a snowball sampling method. Main outcome measure Community pharmacists’ perceptions on safety, resilience, organizational support, and pharmaceutical services offered during COVID-19 pandemic.Results A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitizers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services.  Conclusion The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.

Background: Asthma is a leading cause of pediatric hospitalization in the United States. Children hospitalized with asthma are often cared for in different care settings during a single hospitalization. Our objective was to study the reliability and safety of a new pediatric hospital-wide asthma severity score (HASS) across different care units within a single tertiary-care pediatric center. Methods. 150 patients between the ages of 2 and 18 years hospitalized with a principal diagnosis of status asthmaticus were included. Study patients were followed from initial triage in the emergency department until the time of medical readiness for discharge. Rates of medical errors, early transfers to a higher level of care and medically indicated hospital length of stay (LOS) were compared between 75 patients prior to and 75 patients after implementation of the HASS using retrospective chart review. Inter-rater reliability was determined by collecting independent HASS scores from blinded staff members after tandem or simultaneous patient assessment. Results. Inter-rater reliability among untrained staff members using the HASS was high. Rates of preventable adverse events and medical errors were low and not significantly different before and after implementation of the HASS. LOS was shorter after implementation of the HASS but without statistical significance. Rates of early transfer to a higher level of care were unchanged between study years. Conclusion. The HASS is a reliable asthma severity tool that can be used throughout hospitalization and also among multiple clinical providers to trend clinical progress and optimize communication, particularly during times of care handoffs.

Vaccination is a critical tool in the prevention of COVID-19 infection for individuals and for communities. The mRNA vaccines contain polyethylene glycol (PEG) as a stabilizer. Currently in North America only the BNT162b2 (Pfizer-BioNTech) mRNA vaccine is approved individuals 12 to 17 years of age. Most patients treated with contemporary regimens for acute lymphoblastic leukemia receive Peg-asparaginase and 10-30% will develop allergic reactions. Optimizing access and safety for vaccine administration for these patients critical. This report describes a process developed to support COVID vaccination in a cohort of adolescents and young adults with a history of PEG-asparaginase allergy.

Abstract: Background: The European Academy of Allergy and Clinical Immunology’s (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. Methods: We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 st October 2012 and 30 th June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full-texts, and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta analyses were undertaken for food-test combination where 3 or more studies were available. Results: 149 studies comprising 24,489 patients met the inclusion criteria and were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% undertaken in Europe, ≥95% conducted in a specialized pediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% DBPCFC. Skin prick test (SPT) with fresh cow’s milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE to individual components had high specificity: Ara h 2 had 92%, Cor a 14 95%, Ana o 3 94%, casein 93%, ovomucoid 92/91% for the diagnosis of peanut, hazelnut, cashew, cow’s milk and raw/cooked egg allergies, respectively. BAT was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. Conclusions: SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies. PROSPERO registration: CRD42021259186 Funding: European Academy of Allergy (EAACI).

The manifestations of COVID-19 as outlined by echocardiography, lung ultrasound (LUS) and cardiac magnetic resonance (CMR) imaging are yet to be fully described. We conducted a systematic review of the current literature and included studies that described cardiovascular manifestations of COVID-19 using echocardiography, LUS and CMR. We queried PubMed, EMBASE and Web of Science for relevant articles. Original studies and case series were included. This review describes the most common abnormalities encountered on echocardiography, LUS and CMR in patients infected with COVID-19.

Background and Purpose: Traumatic hemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of TCA inhibitor (nomacopan) on organ damage and survival in vivo. Experimental Approach: Complement activation products and cytokines were analyzed in plasma from 54 combat casualties, and the correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administrated to rats subjected to lethal TH (blast injury and hemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiologic parameters, and laboratory profiles. Key Results: Early TCA was found to be associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with severity of tissue damage and mortality. The addition of nomacopan to a damage control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved hemodynamics and metabolism, attenuated tissue and organ damage, and increased survival. Conclusion and Implications: Our findings reveal that early TCA represents a rational therapeutic target for trauma patients; and nomacopan as a prosurvival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.

To the Editor, Severe asthma (SA) is a chronic disease affecting around 3-8% of adult asthma population in Europe, with the refractory form estimated to occur in 0.1% of the general population (1,2). SA is characterized by increased use of healthcare resources (i.e. emergency room/hospital admissions, access to intensive care units (ICU), use of biologics) due to exacerbations compared to the less severe form. In the current SARS-CoV-2 pandemic, there is an ongoing debate on the role of asthma and use of immunomodulating drugs, like corticosteroids and biologics, on COVID-19 outcomes. According to available data on COVID-19 hospitalizations, asthma seems to play little role on the clinical severity or access to health resources, unlike other chronic conditions such as hypertension, obesity and chronic obstructive pulmonary disease (3). However, to date, no information is available on the burden of SA on COVID-19 severity and hospitalization rates.A questionnaire was submitted to the Italian Registry of Severe Asthma (IRSA) network (4), assessing the prevalence and clinical characteristics of patients with SA who contracted COVID-19 during the outbreak in Italy (February 24th - May 18th 2020), and 41 out of 78 centers distributed evenly among different Italian regions participated to the survey (Figure 1a).Among the 558 subjects surveyed, 7 subjects contracted COVID-19 (1.25% of the national sample), with an average age of 54.5 years: 5 isolated at home/received home care (71.5%), while 2 subjects were admitted to the hospital (28.5%), none required accessed to ICU and no deaths were reported. All COVID-19 subjects with SA came from 2 regions of Northern Italy (6 Lombardy, 1 Emilia-Romagna, 3.7% of the regional population), all showing one or more comorbidities, and were treated with high-dose inhaled corticosteroids plus long-acting beta-2 agonists (ICS-LABA) and biologics (see Table 1).We then compared our results with data provided by the Italian Department for Civil Protection in the same time period from the affected geographic areas (5), and we observed that the frequency of COVID-19 among subjects referred to IRSA centers strongly correlated with the prevalence of SARS-CoV-2 infection in the corresponding province (Figure 1b). Furthermore, the hospitalization rate in COVID-19-SA subjects was not significantly different from the general population (24.1%, 23.6-24.6 95% C.I.; p=0.25, Chi-squared test). Lastly, we could not observe a significantly increased COVID-19 frequency in subjects undergoing high-dose ICS-LABA and biologics compared to SA treated with ICS-LABA alone (p=0.09, Fisher exact test).These findings from the IRSA registry offer some insights on the susceptibility to SARS-CoV-2 infection, access to healthcare resources and mortality by SA patients.Given the low prevalence of SA in Italy (2), we expected less COVID-19-SA cases per region than what reported by the IRSA survey. However, we observed that the geographic location of COVID-19-SA patients mostly reflected the bimodal distribution of the COVID-19 outbreak in Italy, mainly clustered in Lombardy and neighboring regions, where the highest cumulative COVID-19 cases were recorded (>500/100000 cases per inhabitants) (5). In these areas, the prevalence of positive cases by province also strongly correlated with the frequency of COVID-19-SA patients observed in each IRSA center (Figure 1b), suggesting that patients with SA most likely contract the infection when high circulation of the virus within the area of residence is present. The lack of positive cases reported in Southern regions further proves this hypothesis, and demonstrates the efficacy of the lockdown measures adopted to contain the further spread of the virus.Our results also suggest no increased risk of contracting COVID-19 in SA treated with biologics compared to ICS-LABA alone. Although there is currently no strong evidence that biologics used in asthma might affect the risk of contracting COVID-19, new evidence suggests a protective effect of inhaled corticosteroids against viral entry by ACE2 receptor downregulation, that are usually prescribed at a high dose in SA (6), thus a possible explanation to the lack of observed differences in our cohort.Despite the severity of asthma and reported comorbidities, no ICU admissions were reported, and hospital admissions in COVID-19-SA subjects did not differ from the median rate observed in the same geographic areas (5). Furthermore, we could observe no difference in the median monthly hospitalization rate of SA patients in 2019 compared to 2020 in Lombardy region where both hospital-admitted subjects reside (0.97 vs 0.9%, IRSA data).Our result is consistent with recent literature, showing that asthma in Western countries was not associated with an increased hospitalization rate and ICU admissions due to COVID-19 (3,8). It is still debated if a protective effect of Th2-inflammation in a significant proportion of asthma sufferers (7), or concomitant anti-inflammatory therapy could be the reasons for such outcomes (6). However, if asthma patients with COVID-19 require intubation, the duration of hospitalization was shown to be longer than average (8).As for the role of biologics in COVID-19 disease progression, we could not observe an increase in hospital admissions in patients with SA treated with biologics compared to the general population, with the majority isolating at home and requiring no additional treatment. Considering that, in areas with high prevalence of SARS-CoV-2 infection, 68.2% of SA subjects were treated with either omalizumab or mepolizumab, our observations further prove the safety of biologics during the COVID-19 pandemic.Lastly, we did not observe any deaths in our cohort, but we speculate that this outcome is most likely due to the small sample size and younger average age. In fact, advanced age seems to be the most determining risk factor on mortality due to COVID-19 compared to other causes. (9)Taken together, our results point at a neutral role of SA in the COVID-19 disease course and hospital admissions. One major strengths of our study is that, by using a fast and inexpensive tool, we could outline the salient features of severe asthma and COVID-19 at a national level, while the major weakness is the limited number of SA subjects diagnosed with COVID-19, that could lead to sampling bias and low accuracy. Further confirmation of these results with an increased sample size is therefore warranted

The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by Mannan-binding lectin resulting in lectin pathway-activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition in endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Strikingly, SARS-CoV-2-infected African Americans suffer from high mortality. Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi-organ injury. These findings allow us to apply our knowledge from other complement-mediated diseases to COVID-19 infection to better understand severe disease pathogenesis. Here we will discuss the multiple aspects of complement activation, regulation, crosstalk with other parts of the immune system and the options to target complement in COVID-19 patients to halt disease progression and death.

Hundreds of researchers are working to develop a vaccine and are evaluating drugs to mitigate the adverse health and economic consequences of COVID-19 (Coronavirus disease 19) worldwide. If novel compounds are found, geopolitical and economic variables will determine their introduction to communities. Therefore, finding low-cost and widely accessible drugs for prevention or treatment of COVID-19 would be ideal.A recent study found that ivermectin, an FDA-approved anti-parasitic drug, has inhibitory effects on replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Ivermectin has broad anti-viral activity through inhibition of viral proteins including importin α/β1 heterodimer and integrase protein2. Caly and colleagues reported that the addition of ivermectin at a concentration of 5 micromolar (μM) (twice the reported IC50) to Vero-hSLAM cells, 2 hours post infection with SARS-CoV-2, resulted in a reduction in the viral RNA load by 99.98% at 48 hours1. The authors suggested that this drug could reduce the viral load in infected patients, with potential effect on disease progression and spread.While the findings by Caly and colleagues provide some promise, there is no evidence that the 5 μM concentration of ivermectin used by Caly and colleagues in their in vitro SARS-CoV-2 experiment, can be achieved in vivo . The pharmacokinetics of ivermectin in humans is well described (Figure 1)3-5, and even with the highest reported dose of approximately 1700 µg/kg (i.e. 8.5 times the FDA-approved dose of 200 μg/kg), the maximum plasma concentration was only 0.28 µM5. This is 18 times lower than the concentration required to reduce viral replication of SARS-CoV-2in vitro . Ivermectin accumulation in tissues is mild and would not be sufficient to achieve the antiviral effect with conventional doses6. Although high doses of ivermectin in adults or children are well tolerated5,7, the clinical effects of ivermectin at a concentration of 5 μM range are unknown and may be associated with toxicity. Consequently, ivermectin has in vitroactivity against SARS-CoV-2 but this effect is unlikely to be observedin vivo using current dosing.Amidst fear of the pandemic, the public and some physicians are now using ivermectin off-label for prophylaxis or as adjuvant therapy for COVID-19. Because ivermectin is only commercially available as a 3 or 6 mg tablets or a 6 mg/ml oral suspension, in order to administer a high dose, some people may experiment with more concentrated veterinary formulations. These actions are not based on clinical trials and have motivated cautionary statements from institutions such as the FDA against the use of pharmaceutical formulations of ivermectin intended for animals as therapeutics in humans 8.Potential avenues for further investigation into repurposing ivermectin for SARS-CoV-2 may be to: (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure; and (ii) evaluate more potent ivermectin analogs (e.g. doramectin) which may also inhibit SARS-CoV-2. These are areas for research – clearly, further studies are needed before ivermectin can be used for the prevention and treatment of COVID-19. As recently discussed in BJCP, this highlights the critical need to consider pharmacological principles to guide in vitro testing when repurposing old drugs for therapeutic use against COVID-199.