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BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

We found no significant difference in cycle threshold values between vaccinated and unvaccinated persons infected with severe acute respiratory syndrome coronavirus 2 Delta, overall or stratified by symptoms. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered in settings with elevated coronavirus disease 2019 transmission.

BackgroundAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased risk of adverse perinatal health outcomes, few large-scale, community-based epidemiological studies have been conducted.MethodsWe conducted a national cohort study using deidentified administrative claims data for 78 283 pregnancies with estimated conception before 30 April 2020 and pregnancy end after 11 March 2020. We identified SARS-CoV-2 infections using diagnostic and laboratory testing data, and compared the risk of pregnancy outcomes using Cox proportional hazard models treating coronavirus disease 2019 (COVID-19) as a time-varying exposure and adjusting for baseline covariates.ResultsOf the pregnancies, 2655 (3.4%) had a documented SARS-CoV-2 infection. COVID-19 during pregnancy was not associated with risk of miscarriage, antepartum hemorrhage, or stillbirth, but was associated with 2-3 fold higher risk of induced abortion (adjusted hazard ratio [aHR], 2.60; 95% confidence interval [CI], 1.17-5.78), cesarean delivery (aHR, 1.99; 95% CI, 1.71-2.31), clinician-initiated preterm birth (aHR, 2.88; 95% CI, 1.93-4.30), spontaneous preterm birth (aHR, 1.79; 95% CI, 1.37-2.34), and fetal growth restriction (aHR, 2.04; 95% CI, 1.72-2.43).ConclusionsPrenatal SARS-CoV-2 infection was associated with increased risk of adverse pregnancy outcomes. Prevention could have fetal health benefits.

BackgroundFollowing the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country.MethodsNasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced.ResultsOverall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39 years (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses.ConclusionsOur study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.

The majority of crystal structures are determined by the method of molecular replacement (MR). The range of application of MR is limited mainly by the need for an accurate search model. In most cases, pre-existing experimentally determined structures are used as search models. In favorable cases, ab initio predicted structures have yielded search models adequate for MR. The ORF8 protein of SARS-CoV-2 represents a challenging case for MR using an ab initio prediction because ORF8 has an all β-sheet fold and few orthologs. We previously determined experimentally the structure of ORF8 using the single anomalous dispersion (SAD) phasing method, having been unable to find an MR solution to the crystallographic phase problem. Following a report of an accurate prediction of the ORF8 structure, we assessed whether the predicted model would have succeeded as an MR search model. A phase problem solution was found, and the resulting structure was refined, yielding structural parameters equivalent to the original experimental solution.

The COVID-19 pandemic has disrupted many standard approaches to STEM education. Particularly impacted were field courses, which rely on specific natural spaces often accessed through shared vehicles. As in-person field courses have been found to be particularly impactful for undergraduate student success in the sciences, we aimed to compare and understand what factors may have been lost or gained during the conversion of an introductory field course to an online format. Using a mixed methods approach comparing data from online and in-person field-course offerings, we found that while community building was lost in the online format, online participants reported increased self-efficacy in research and observation skills and connection to their local space. The online field course additionally provided positive mental health breaks for students who described the time outside as a much-needed respite. We maintain that through intentional design, online field courses can provide participants with similar outcomes to in-person field courses.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.

ObjectivesThe objective was to provide a longitudinal assessment of anxiety levels and work and home concerns of U.S. emergency physicians during the COVID-19 pandemic.MethodsWe performed a longitudinal, cross-sectional email survey of clinically active emergency physicians (attending, fellow, and resident) at seven academic emergency departments. Follow-up surveys were sent 4 to 6 weeks after the initial survey and assessed the following: COVID-19 patient exposure, availability of COVID-19 testing, levels of home and workplace anxiety/stress, changes in behaviors, and performance on a primary care posttraumatic stress disorder screen (PC-PTSD-5). Logistic regression explored factors associated with a high PC-PTSD-5 scale score (≥3), indicating increased risk for PTSD.ResultsOf the 426 surveyed initial respondents, 262 (61.5%) completed the follow-up survey. While 97.3% (255/262) reported treating suspected COVID-19 patients, most physicians (162/262, 61.8%) had not received testing themselves. In follow-up, respondents were most concerned about the relaxing of social distancing leading to a second wave (median score = 6, IQR = 4-7). Physicians reported a consistently high ability to order COVID-19 tests for patients (median score = 6, IQR = 5-7) and access to personal protective equipment (median score = 6, IQR = 5-6). Women physicians were more likely to score ≥ 3 than men on the PC-PTSD-5 screener on the initial survey (43.3% vs. 22.5%; Δ 20.8%, 95% confidence interval [CI] = 9.3% to 31.5%), and despite decreases in overall proportions, this discrepancy remained in follow-up (34.7% vs. 16.8%; Δ 17.9%, 95% CI = 7.1% to 28.1%). In examining the relationship between demographics, living situations, and institution location on having a PC-PTSD-5 score ≥ 3, only female sex was associated with a PC-PTSD-5 score ≥ 3 (adjusted odds ratio = 2.48, 95% CI = 1.28 to 4.79).ConclusionsWhile exposure to suspected COVID-19 patients was nearly universal, stress levels in emergency physicians decreased with time. At both initial and follow-up assessments, women were more likely to test positive on the PC-PTSD-5 screener compared to men.

The recurring translocation t(1;19) (q23;p13) with TCF3-PBX1 rearrangements are uncommon in adult acute lymphoblastic leukemia (ALL), and their prognostic impact remains to be described in the era of modern chemotherapies. We investigated 427 adult patients with newly diagnosed pre-B ALL, 16 (4%) had t(1;19)(q23;p13) at diagnosis. All 16 patients achieved complete remission after induction with intensive chemotherapy, and with a median of 7-year follow-up, 2 relapsed. The 5-year cumulative incidence of relapse and overall survival rates were 14% and 82%, respectively. Our analysis showed that adult patients with t(1;19)(q23;p13) positive ALL had favorable prognosis with intensive chemotherapy regimens.

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.

IntroductionKey populations at elevated risk to contract or transmit HIV may also be at higher risk of COVID-19 complications and adverse outcomes associated with public health prevention measures. However, the conditions faced by specific populations vary according to social, structural and environmental factors, including stigma and discrimination, criminalization, social and economic safety nets and the local epidemiology of HIV and COVID-19, which determine risk of exposure and vulnerability to adverse health outcomes, as well as the ability to comply with measures such as physical distancing. This commentary identifies common vulnerabilities and cross-cutting themes in terms of the impacts of COVID-19 on key populations before addressing issues and concerns specific to particular populations.DiscussionCross-cutting themes include direct impacts such as disrupted access to essential medicines, commodities and services such as anti-retroviral treatment, HIV pre-exposure prophylaxis, opioid agonist treatment, viral load monitoring, HIV and sexually transmitted infections testing, condoms and syringes. Indirect impacts include significant collateral damage arising from prevention measures which restrict human rights, increase or impose criminal penalties, and expand police powers to target vulnerable and criminalized populations. Significant heterogeneity in the COVID-19 pandemic, the underlying HIV epidemic and the ability of key populations to protect themselves means that people who inject drugs and sex workers face particular challenges, including indirect impacts as a result of police targeting, loss of income and sometimes both. Geographical variations mean that transgender people and men who have sex with men in regions like Africa and the middle east remain criminalized, as well as stigmatized and discriminated against, increasing their vulnerability to adverse outcomes in relation to COVID-19.ConclusionsDisruptions to both licit and illicit supply chains, loss of income and livelihoods and changes in behaviour as a result of lockdowns and physical distancing have the potential to exacerbate the impacts of the COVID-19 pandemic on key populations. While these impacts will vary significantly, human-rights approaches to COVID-19 emergency laws and public health prevention measures that are population-specific and sensitive, will be key to reducing adverse health outcomes and ensuring that no one is left behind.

Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and antihypertensive arachidonic acid epoxides, epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic stabilization with a sEH inhibitor to be most effective in lowering BP, although both TPPU and 19, 20-EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.