The impact of yeast-encapsulated orange oil in Aedes aegypti oviposition.

The yeast-encapsulated orange oil (YEOO) is a novel larvicide under development against vector mosquitoes. Despite its efficiency against Aedes aegypti (L.) in small scale experiments, its applicability in vector control can be influenced by other effects on mosquito behaviour or physiology. For this reason, the impact of YEOO particles in mosquito oviposition was evaluated in laboratory and semi-field conditions. Oviposition assays with one gravid Aedes aegypti female were carried under laboratory and semi-field conditions with natural light and temperature fluctuation. For all ovitraps, the number of eggs was manually counted in the wooden paddle and in the solution of each ovitrap. The proportion of eggs between substrates (wooden paddle and solution) varied between conditions, with females in laboratory presenting a lower preference to lay eggs in paddles when compared with studies in semi-field. This behaviour shifts in laboratory can create challenges to extrapolate results from laboratory to the field. Here, studies in both conditions indicate a similar impact of YEOO particles in Aedes aegypti oviposition. The potential treatment concentration of YEOO particles presents a strong repellent/deterrent effect (-0.559 > OAI > -0.760) within the initial 72h of application when compared with water, and weak repellent/deterrent signal (OAI = -0.220) when compared against inactivated yeast. Control ovitraps with water were more positive for egg presence than treated ovitraps, while ovitraps with YEOO particles and inactivated yeast present similar number of positive ovitraps. It is possible that the repellent/deterrent action is partially driven by the delivery system, since most times Citrus sinensis EO oviposition repellent/deterrent signal is weak, and it seem influenced by solvent/delivery used. However, it is unclear how the yeast wall that protect/surrounds the orange oil will negatively affect oviposition since live yeast are normally consider an attractant for mosquito oviposition.

Disproportionate impact of COVID-19 severity and mortality on hospitalized American Indian/Alaska Native patients.

Epidemiological data across the United States of America illustrate health disparities in COVID-19 infection, hospitalization, and mortality by race/ethnicity. However, limited information is available from prospective observational studies in hospitalized patients, particularly for American Indian or Alaska Native (AI/AN) populations. Here, we present risk factors associated with severe COVID-19 and mortality in patients (4/2020-12/2021, n = 475) at the University of New Mexico Hospital. Data were collected on patient demographics, infection duration, laboratory measures, comorbidities, treatment(s), major clinical events, and in-hospital mortality. Severe disease was defined by COVID-related intensive care unit requirements and/or death. The cohort was stratified by self-reported race/ethnicity: AI/AN (30.7%), Hispanic (47.0%), non-Hispanic White (NHW, 18.5%), and Other (4.0%, not included in statistical comparisons). Despite similar timing of infection and comparable comorbidities, admission characteristics for AI/AN patients included younger age (P = 0.02), higher invasive mechanical ventilation requirements (P = 0.0001), and laboratory values indicative of more severe disease. Throughout hospitalization, the AI/AN group also experienced elevated invasive mechanical ventilation (P < 0.0001), shock (P = 0.01), encephalopathy (P = 0.02), and severe COVID-19 (P = 0.0002), consistent with longer hospitalization (P < 0.0001). Self-reported AI/AN race/ethnicity emerged as the highest risk factor for severe COVID-19 (OR = 3.19; 95% CI = 1.70-6.01; P = 0.0003) and was a predictor of in-hospital mortality (OR = 2.35; 95% CI = 1.12-4.92; P = 0.02). Results from this study highlight the disproportionate impact of COVID-19 on hospitalized AI/AN patients, who experienced more severe illness and associated mortality, compared to Hispanic and NHW patients, even when accounting for symptom onset and comorbid conditions. These findings underscore the need for interventions and resources to address health disparities in the COVID-19 pandemic.

Defining the mechanisms of action and mosquito larva midgut response to a yeast-encapsulated orange oil larvicide.

BACKGROUND: Yeast-encapsulated orange oil (YEOO) is a novel, ingestible larvicide that combines the benefits of a low-cost essential oil with yeast, an attractive food source for mosquito larvae. In this work, we investigated the underlying mechanisms of action associated with YEOO ingestion by Aedes aegypti larvae. METHODS: Aedes aegypti third-stage larvae (L3) were treated with sublethal or lethal concentrations of YEOO. Genes associated with apoptosis, autophagy and innate immune responses were investigated by RT-qPCR in guts and carcasses dissected from treated and control larvae. Differential expression of cytochrome P450 genes in the CYP6 and CYP9 families were also investigated. Confocal and transmission electron microscopy were used to assess damage caused by YEOO throughout the larval alimentary canal. TUNEL was used to assess apoptosis via DNA fragmentation. RESULTS: The apoptosis genes IAP1 and IAP2 in larvae displayed opposing effects following exposure to lethal doses of YEOO, with a 26-fold induction of IAP1 at 8 h post YEOO ingestion. The effector caspase CASPS8 displayed a 6.7-fold induction in the gut and concomitant 70-fold induction in the carcass at 8 h post YEOO ingestion. The midgut epithelia regenerator, Vein, had an 11-fold induction in the gut after 4 h and was repressed 7.6-fold in the carcass at 24 h. Sublethal concentrations (< LC50) led to significant differential expression of CYP6 and CYP9 genes. Midgut epithelial damage was highlighted by the destruction of microvilli, vacuolization of midgut cells and damage to cell junctions and basal lamina as early as 30 min. Larval type 2 peritrophic matrix structural integrity and porosity remain unchanged. CONCLUSION: Our results strongly suggest that the robust larvicidal activity of YEOO is due to a generalized broad-acting mechanism combining epithelial damage and apoptosis, with concomitant expression of multiple innate response genes involved in epithelial regeneration and detoxification. YEOO's amenability for use as part of an integrated vector management program makes this novel larvicide a practical approach for mosquito larval control in the future.

Elevated SARS-CoV-2 in peripheral blood and increased COVID-19 severity in American Indians/Alaska Natives.

Epidemiological data across the United States show health disparities in COVID-19 infection, hospitalization, and mortality by race/ethnicity. While the association between elevated SARS-CoV-2 viral loads (VLs) (i.e. upper respiratory tract (URT) and peripheral blood (PB)) and increased COVID-19 severity has been reported, data remain largely unavailable for some disproportionately impacted racial/ethnic groups, particularly for American Indian or Alaska Native (AI/AN) populations. As such, we determined the relationship between SARS-CoV-2 VL dynamics and disease severity in a diverse cohort of hospitalized patients. Results presented here are for study participants (n = 94, ages 21-88 years) enrolled in a prospective observational study between May and October 2020 who had SARS-CoV-2 viral clades 20A, C, and G. Based on self-reported race/ethnicity and sample size distribution, the cohort was stratified into two groups: (AI/AN, n = 43) and all other races/ethnicities combined (non-AI/AN, n = 51). SARS-CoV-2 VLs were quantified in the URT and PB on days 0-3, 6, 9, and 14. The strongest predictor of severe COVID-19 in the study population was the mean VL in PB (OR = 3.34; P = 2.00 × 10-4). The AI/AN group had the following: (1) comparable co-morbidities and admission laboratory values, yet more severe COVID-19 (OR = 4.81; P = 0.014); (2) a 2.1 longer duration of hospital stay (P = 0.023); and (3) higher initial and cumulative PB VLs during severe disease (P = 0.025). Moreover, self-reported race/ethnicity as AI/AN was the strongest predictor of elevated PB VLs (ß = 1.08; P = 6.00 × 10-4) and detection of SARS-CoV-2 in PB (hazard ratio = 3.58; P = 0.004). The findings presented here suggest a strong relationship between PB VL (magnitude and frequency) and severe COVID-19, particularly for the AI/AN group.

A Comprehensive COVID-19 Daily News and Medical Literature Briefing to Inform Health Care and Policy in New Mexico: Implementation Study.

BACKGROUND: On March 11, 2020, the New Mexico Governor declared a public health emergency in response to the COVID-19 pandemic. The New Mexico medical advisory team contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease to facilitate New Mexico's pandemic management. Thus, faculty, physicians, staff, graduate students, and medical students created the "UNM Global Health COVID-19 Intelligence Briefing." OBJECTIVE: In this paper, we sought to (1) share how to create an informative briefing to guide public policy and medical practice and manage information overload with rapidly evolving scientific evidence; (2) determine the qualitative usefulness of the briefing to its readers; and (3) determine the qualitative effect this project has had on virtual medical education. METHODS: Microsoft Teams was used for manual and automated capture of COVID-19 articles and composition of briefings. Multilevel triaging saved impactful articles to be reviewed, and priority was placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and information on health care and policy response to COVID-19. The finalized briefing was disseminated by email, a listserv, and posted on the UNM digital repository. A survey was sent to readers to determine briefing usefulness and whether it led to policy or medical practice changes. Medical students, unable to partake in direct patient care, proposed to the School of Medicine that involvement in the briefing should count as course credit, which was approved. The maintenance of medical student involvement in the briefings as well as this publication was led by medical students. RESULTS: An average of 456 articles were assessed daily. The briefings reached approximately 1000 people by email and listserv directly, with an unknown amount of forwarding. Digital repository tracking showed 5047 downloads across 116 countries as of July 5, 2020. The survey found 108 (95%) of 114 participants gained relevant knowledge, 90 (79%) believed it decreased misinformation, 27 (24%) used the briefing as their primary source of information, and 90 (79%) forwarded it to colleagues. Specific and impactful public policy decisions were informed based on the briefing. Medical students reported that the project allowed them to improve on their scientific literature assessment, stay current on the pandemic, and serve their community. CONCLUSIONS: The COVID-19 briefings succeeded in informing and guiding New Mexico policy and clinical practice. The project received positive feedback from the community and was shown to decrease information burden and misinformation. The virtual platforms allowed for the continuation of medical education. Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing led by faculty.

COVID-19 global pandemic planning: Presence of SARS-CoV-2 fomites in a university hospital setting.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has surged across the globe, great effort has been expended to understand mechanisms of transmission and spread. From a hospital perspective, this topic is critical to limit and prevent SARS-CoV-2 iatrogenic transmission within the healthcare environment. Currently, the virus is believed to be transmitted primarily through respiratory droplets, but a growing body of evidence suggests that spread is also possible through aerosolized particles and fomites. Amidst a growing volume of patients with coronavirus disease 2019 (COVID-19), the purpose of this study was to evaluate the potential for SARS-CoV-2 transmission through fomites. Samples collected from the exposed skin of clinicians (n = 42) and high-touch surfaces (n = 40) were collected before and after encounters with COVID-19 patients. Samples were analyzed using two assays: the CDC 2019-nCoV Real-Time Reverse Transcription polymerase chain reaction (RT-qPCR) assay, and a SYBR Green assay that targeted a 121 bp region within the S-gene of SARS-CoV-2. None of the samples tested positive with the CDC assay, while two high-touch surface areas tested positive for SARS-CoV-2 using the Spike assay. However, viral culture did not reveal viable SARS-CoV-2 from the positive samples. Overall, the results from this study suggest that SARS-CoV-2 RNA were not widely present either on exposed skin flora or high-touch surface areas in the hospital locations tested. The inability to recover viable virus from samples that tested positive by the molecular assays, however, does not rule out the possibility of SARS-CoV-2 transmission through fomites.

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers in Convalescent Plasma and Recipients in New Mexico: An Open Treatment Study in Patients With Coronavirus Disease 2019.

BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway. METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. RESULTS: NAb titers in the donor CP units were low (<1:40 to 1:160) and had no effect on recipient neutralizing activity 1 day after transfusion. NAb titers were detected in 6 of 12 patients on enrollment and in 11 of 12 at ≥2 time points. Average titers peaked on day 7 and declined toward day 14 (P = .004). Nab titers and immunoglobulin G levels were correlated in donor plasma units (ρ = 0.938; P < .001) and in the cumulative patient measures (ρ = 0.781; P < .001). CONCLUSIONS: CP infusion did not alter recipient NAb titers. Prescreening of CP may be necessary for selecting donors with high titers of neutralizing activity for infusion into patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04434131.