The SHIELD Study: A preliminary analysis of nasal and oral antisepsis to prevent COVID-19

Background: Povidone-iodine and chlorhexidine gluconate are commonly used antiseptics that have broad antiviral properties, including against SARS-CoV-2. Nasal and oral antisepsis is a possible option to reduce viral transmission;however, effectiveness data are limited. The acceptability of this method for adjunct infection control is also unknown. We are conducting a clinical randomized controlled trial (NCT04478019) to evaluate the effectiveness and feasibility of nasal and oral antisepsis to prevent COVID-19. Methods: Healthcare and other essential workers with in-person job duties were recruited into a 10-week clinical trial. Participation did not require in-person activities: all communication was web- or telephone-based, supplies were shipped directly to the participant, and participants self-collected specimens. Participants completed a 3-week intervention and 3-week control phases and were randomized to the timing of these phases (Fig. 1). During the 3-week intervention phase, participants applied povidone-iodine nasal swabs 2 times per day and chlorhexidine gluconate oral rinse 4 times per day following the manufacturers' instructions for use. Participants continued all usual infection control measures (eg, face masks, eye protection, gowns, hand hygiene) as required by their workplace. To measure effectiveness against viral transmission, participants collected midturbinate nasal swabs 3 times per week to measure SARS-CoV-2 viral load. Participants also self-reported COVID-19 tests they received and why (eg, symptoms or exposure). To assess acceptability, participants completed pre- and post-surveys about their perceived and actual experience with the interventions. Participants also self-reported adverse effects due to the intervention. Results: As of December 3, 2021, 221 participants (148 healthcare workers and 73 non–healthcare essential workers) had enrolled. Moreover, 20 adverse effects have been reported, including skin irritation, epistaxis, and mouth discoloration;9 participants withdrew due to side effects. Laboratory analyses are ongoing to measure effectiveness in reducing SARS-CoV-2 viral load. We performed an interim analysis of intervention acceptability. Survey responses were given on a Likert scale of 1 (not at all) to 5 (extremely). Although 36% of respondents (n = 74) reported on the postsurvey that the intervention was less acceptable than they had expected on the presurvey, the overall acceptability measure was still relatively high (3.76) (Fig. 2). In addition, 76% of respondents reported that they would use the intervention in the future (n = 56). Conclusions: Participant recruitment is ongoing, and data continue to be collected to analyze effectiveness and feasibility. Preliminary data suggest that participants find the nasal and oral antisepsis intervention to be an acceptable option to complement standard infection control methods to prevent COVID-19.Funding: Professional Disposables International, Healthcare Division (PDIHC)Disclosures: None

Dose of aspirin to prevent preterm preeclampsia in women with moderate or high-risk factors: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of aspirin dose on the incidence of all gestational age preeclampsia and preterm preeclampsia. DATA SOURCES: Electronic databases (Cochrane, PubMed, Scopus, ClinicalTrials.gov and the Web of Science) were searched for articles published between January 1985 and March 2019 with no language restrictions. METHODS: We followed the PRIMSA guidelines and utilized Covidence software. Articles were screened by 2 independent reviewers, with discrepancies settled by an independent 3rd party. Study selection criteria were randomized trials comparing aspirin for prevention of all gestational age and preterm preeclampsia to placebo or no antiplatelet treatment in women aged 15-55 years with moderate or high-risk factors according to the list of risk factors from American College of Obstetricians and Gynecologists and United States Preventive Services Task Force guidelines. The quality of trials was assessed using the Cochrane risk of bias tool. The data were pooled using a random-effects meta-analysis comparing aspirin at doses of <81, 81, 100, and 150 mg. Pre-specified outcomes were all gestational age and preterm preeclampsia. RESULTS: Of 1,609 articles screened, 23 randomized trials, which included 32,370 women, fulfilled the inclusion criteria. In preterm preeclampsia, women assigned at random to 150 mg experienced a significant 62% reduction in risk of preterm preeclampsia (RR = 0.38; 95% CI: 0.20-0.72; P = 0.011). Aspirin doses <150 mg produced no significant reductions. The number needed to treat with 150 mg of aspirin was 39 (95% CI: 23-100). There was a maximum 30% reduction in risk of all gestational age preeclampsia at all aspirin doses. CONCLUSIONS: In this meta-analysis, based on indirect comparisons, aspirin at a dose greater than the current, recommended 81 mg was associated with the highest reduction in preterm preeclampsia. Our meta-analysis is limited due to the deficiency of homogeneous high evidence data available in the literature to date; however, it may be prudent for clinicians to consider that the optimal aspirin dose may be higher than the current guidelines advise. Future research to compare the efficacy aspirin doses greater than 81 mg is recommended. STUDY REGISTRATION: PROSPERO, CRD42019127951 (University of York, UK; http://www.crd.york.ac.uk/PROSPERO/).

Optimizing Flow Cytometric Analysis of Immune Cells in Samples Requiring Cryopreservation from Tumor-Bearing Mice.

Most shared resource flow cytometry facilities do not permit analysis of radioactive samples. We are investigating low-dose molecular targeted radionuclide therapy (MTRT) as an immunomodulator in combination with in situ tumor vaccines and need to analyze radioactive samples from MTRT-treated mice using flow cytometry. Further, the sudden shutdown of core facilities in response to the COVID-19 pandemic has created an unprecedented work stoppage. In these and other research settings, a robust and reliable means of cryopreservation of immune samples is required. We evaluated different fixation and cryopreservation protocols of disaggregated tumor cells with the aim of identifying a protocol for subsequent flow cytometry of the thawed sample, which most accurately reflects the flow cytometric analysis of the tumor immune microenvironment of a freshly disaggregated and analyzed sample. Cohorts of C57BL/6 mice bearing B78 melanoma tumors were evaluated using dual lymphoid and myeloid immunophenotyping panels involving fixation and cryopreservation at three distinct points during the workflow. Results demonstrate that freezing samples after all staining and fixation are completed most accurately matches the results from noncryopreserved equivalent samples. We observed that cryopreservation of living, unfixed cells introduces a nonuniform alteration to PD1 expression. We confirm the utility of our cryopreservation protocol by comparing tumors treated with in situ tumor vaccines, analyzing both fresh and cryopreserved tumor samples with similar results. Last, we use this cryopreservation protocol with radioactive specimens to demonstrate potentially beneficial effector cell changes to the tumor immune microenvironment following administration of a novel MTRT in a dose- and time-dependent manner.

Influenza vaccination: a 'shot' at INVESTing in cardiovascular health.

The link between viral respiratory infection and non-pulmonary organ-specific injury, including cardiac injury, has become increasingly appreciated during the current coronavirus disease 2019 (COVID-19) pandemic. Even prior to the pandemic, however, the association between acute infection with influenza and elevated cardiovascular risk was evident. The recently published results of the NHLBI-funded INfluenza Vaccine to Effectively Stop CardioThoracic Events and Decompensated (INVESTED) trial, a 5200 patient comparative effectiveness study of high-dose vs. standard-dose influenza vaccine to reduce cardiopulmonary events and mortality in a high-risk cardiovascular population, found no difference between strategies. However, the broader implications of influenza vaccine as a strategy to reduce morbidity in high-risk patients remain extremely important, with randomized controlled trial and observational data supporting vaccination in high-risk patients with cardiovascular disease. Given a favourable risk-benefit profile and widespread availability at generally low cost, we contend that influenza vaccination should remain a centrepiece of cardiovascular risk mitigation and describe the broader context of underutilization of this strategy. Few therapeutics in medicine offer seasonal efficacy from a single administration with generally mild, transient side effects, and exceedingly low rates of serious adverse effects. Infection control measures such as physical distancing, hand washing, and the use of masks during the COVID-19 pandemic have already been associated with substantially curtailed incidence of influenza outbreaks across the globe. Appending annual influenza vaccination to these measures represents an important public health and moral imperative.