Just-in-Time In Situ Simulation Training as a Preparedness Measure for the Perioperative Care of COVID-19 Patients.

INTRODUCTION: Routine workflows were redesigned during the first surge of the COVID-19 pandemic to standardize perioperative management of patients and minimize the risk of viral exposure and transmission to staff members. Just-in-time (JIT), in situ simulation training was adopted to implement urgent change, the value of which in a public health crisis has not previously been explored. METHODS: Implementation of workflow changes in the setting of the COVID-19 pandemic was accomplished through JIT, in situ simulation training, delivered over a period of 3 weeks to participants from anesthesia, nursing, and surgery, within our healthcare network. The perceived value of this training method was assessed using a postsimulation training survey, composed of Likert scale assessments and free-text responses. The impact on change in practice was assessed by measuring compliance with new COVID-19 workflows for cases of confirmed or suspected COVID-19 managed in the operating room, between March and August 2020. RESULTS: Postsimulation survey responses collected from 110 of 428 participants (25.7%) demonstrated significant positive shifts along the Likert scale on perceived knowledge of new workflow processes, comfort in adopting them in practice and probability that training would have an impact on future practice (all Ps < 0.001). Free-text responses reflected appreciation for the training being timely, hands-on, and interprofessional. Compliance with new COVID workflows protocols in practice was 95% (121 of 127 cases) and was associated with lower than expected healthcare worker test positive rates (<1%) within the network during this same period. CONCLUSIONS: These findings support JIT, in situ simulation training as a preparedness measure for the perioperative care of COVID-19 patients and demonstrate the value of this approach during public health crises.

High-Throughput Neutralization and Serology Assays Reveal Correlated but Highly Variable Humoral Immune Responses in a Large Population of Individuals Infected with SARS-CoV-2 in the US between March and August 2020.

The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology of infection, as well as an aid in determining the efficacy of interventions, particularly in outbreaks such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because of the assay's rapid scalability and high efficiency, serology measurements that quantify the presence rather than function of serum antibodies often serve as proxies of immune protection. Here, we report the development of a high-throughput, automated fluorescence-based neutralization assay using SARS-CoV-2 virus to quantify neutralizing antibody activity in patient specimens. We performed large-scale testing of over 19,000 COVID-19 convalescent plasma (CCP) samples from patients who had been infected with SARS-CoV-2 between March and August 2020 across the United States. The neutralization capacity of the samples was moderately correlated with serological measurements of anti-receptor-binding domain (RBD) IgG levels. The neutralizing antibody levels within these convalescent-phase serum samples were highly variable against the original USA-WA1/2020 strain with almost 10% of individuals who had had PCR-confirmed SARS-CoV-2 infection having no detectable antibodies either by serology or neutralization, and ~1/3 having no or low neutralizing activity. Discordance between neutralization and serology measurements was mainly due to the presence of non-IgG RBD isotypes. Meanwhile, natural infection with the earliest SARS-CoV-2 strain USA-WA1/2020 resulted in weaker neutralization of subsequent B.1.1.7 (alpha) and the B.1.351 (beta) variants, with 88% of samples having no activity against the BA.1 (omicron) variant. IMPORTANCE The ability to directly measure neutralizing antibodies on live SARS-CoV-2 virus in individuals can play an important role in understanding the efficacy of therapeutic interventions or vaccines. In contrast to functional neutralization assays, serological assays only quantify the presence of antibodies as a proxy of immune protection. Here, we have developed a high-throughput, automated neutralization assay for SARS-CoV-2 and measured the neutralizing activity of ~19,000 COVID-19 convalescent plasma (CCP) samples collected across the United States between March and August of 2020. These data were used to support the FDA's interpretation of CCP efficacy in patients with SARS-CoV-2 infection and their issuance of emergency use authorization of CCP in 2020.

Coronavirus Disease 2019 (COVID-19)-Related Stress and Menstrual Changes.

OBJECTIVE: To evaluate how stress related to the coronavirus disease 2019 (COVID-19) pandemic has affected women's menstrual cycles. We hypothesized that women with high levels of COVID-19-related stress would have more menstrual changes compared with those with lower levels of stress. METHODS: Using a cross-sectional study design, we recruited a representative sample of U.S. adult women of reproductive age (18-45 years) using nonhormonal birth control to participate in an online REDCap (Research Electronic Data Capture, Vanderbilt University) survey. COVID-19-related stress was assessed with the PSS-10-C (COVID-19 Pandemic-related Perceived Stress Scale) and dichotomized as low stress (scores lower than 25) and high stress (scores 25 or higher). Self-reported menstrual outcomes were identified as changes in cycle length, duration, or flow and increased frequency of spotting between cycles. We used χ2 and Fisher exact tests to compare differences in outcome between the two stress groups and logistic regression models for effect estimates. RESULTS: A total of 354 women of reproductive age across the United States completed both the menstrual and COVID-19-related stress components of our survey. More than half of these women reported at least one change in their menstrual cycles since the start of the pandemic (n=191), and 10.5% reported high COVID-19-related stress (n=37). Compared with those with low COVID-19-related stress, a greater proportion of women with high COVID-19-related stress reported changes in cycle length (shorter or longer; P=.008), changes in period duration (shorter or longer; P<.001), heavier menstrual flow (P=.035), and increased frequency of spotting between cycles (P=.006) compared with prepandemic times. After adjusting for age, smoking history, obesity, education, and mental health history, high COVID-19-related stress was associated with increased odds of changes in menstrual cycle length (adjusted odds ratio [aOR] 2.32; 95% CI 1.12-4.85), duration (aOR 2.38; 95% CI 1.14-4.98), and spotting (aOR 2.32; 95% CI 1.03-5.22). Our data also demonstrated a nonsignificant trend of heavier menstrual flow among women with high COVID-19-related stress (aOR 1.61; 95% CI 0.77-3.34). CONCLUSION: High COVID-19-related stress is associated with significant changes in menstrual cycle length, alterations in period duration, and increased intermenstrual spotting as compared with before the pandemic. Given that menstrual health is frequently an indicator of women's overall well-being, clinicians, researchers, and public health officials must consider the association between COVID-19-related stress and menstrual disturbances.

Targeting intracellular Neu1 for coronavirus infection treatment.

There are currently no effective therapies for COVID-19 or antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccines appear less effective against new SARS-CoV-2 variants; thus, there is an urgent need to understand better the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Herein, we show that host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA-binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.

Vaccination Coverage by Age 24 Months Among Children Born During 2018-2019 - National Immunization Survey-Child, United States, 2019-2021.

Millions of young children are vaccinated safely in the United States each year against a variety of potentially dangerous infectious diseases (1). The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination against 14 diseases during the first 24 months of life* (2). This report describes vaccination coverage by age 24 months using data from the National Immunization Survey-Child (NIS-Child).† Compared with coverage among children born during 2016-2017, coverage among children born during 2018-2019 increased for a majority of recommended vaccines. Coverage was >90% for ≥3 doses of poliovirus vaccine (93.4%), ≥3 doses of hepatitis B vaccine (HepB) (92.7%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.6%), and ≥1 dose of varicella vaccine (VAR) (91.1%); coverage was lowest for ≥2 doses of hepatitis A vaccine (HepA) (47.3%). Vaccination coverage overall was similar or higher among children reaching age 24 months during March 2020 or later (during the COVID-19 pandemic) than among those reaching age 24 months before March 2020 (prepandemic); however, coverage with the combined 7-vaccine series§ among children living below the federal poverty level or in rural areas decreased by 4-5 percentage points during the pandemic (3). Among children born during 2018-2019, coverage disparities were observed by race and ethnicity, poverty status, health insurance status, and Metropolitan Statistical Area (MSA) residence. Coverage was typically higher among privately insured children than among children with other insurance or no insurance. Persistent disparities by health insurance status indicate the need to improve access to vaccines through the Vaccines for Children (VFC) program.¶ Providers should review children's histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases.

Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (COVID-19) in several countries. METHODS: We conducted a phase 2, double-blind, randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg BID days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: We randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48-1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54-1.29]; sustained: HR, 0.87 [95% CI, .52-1.45]) and no difference in transition mutation accumulation in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04346628.

Defining and Addressing Anesthesiology Needs in Simulation-based Medical Education.

Background: This study's primary aim was to determine how training programs use simulation-based medical education (SBME), because SBME is linked to superior clinical performance. Methods: An anonymous 10-question survey was distributed to anesthesiology residency program directors across the United States. The survey aimed to assess where and how SBME takes place, which resources are available, frequency of and barriers to its use, and perceived utility of a dedicated departmental education laboratory. Results: The survey response rate was 30.4% (45/148). SBME typically occurred at shared on-campus laboratories, with residents typically participating in SBME 1 to 4 times per year. Frequently practiced skills included airway management, trauma scenarios, nontechnical skills, and ultrasound techniques (all ≥ 77.8%). Frequently cited logistical barriers to simulation laboratory use included COVID-19 precautions (75.6%), scheduling (57.8%), and lack of trainers (48.9%). Several respondents also acknowledged financial barriers. Most respondents believed a dedicated departmental education laboratory would be a useful or very useful resource (77.8%). Conclusion: SBME is a widely incorporated activity but may be impeded by barriers that our survey helped identify. Barriers can be addressed by departmental education laboratories. We discuss how such laboratories increase capabilities to support structured SBME events and how costs can be offset. Other academic departments may also benefit from establishing such laboratories.

A Social Media‒Based Public Health Campaign Encouraging COVID-19 Vaccination Across the United States.

Tailored public health messaging encouraging COVID-19 vaccination may help increase vaccination rates and decrease the burden of COVID-19. We conducted a three-part COVID-19 vaccine uptake public health campaign disseminated on Facebook between April and June 2021. Our first campaign focused on reaching Black and Latinx communities; our second campaign focused on addressing vaccine access and scheduling in Latinx communities; and our third campaign focused on religious communities. Overall, we reached 25 million individuals with 171 million views across the United States. (Am J Public Health. 2022;112(9):1253-1256. https://doi.org/10.2105/AJPH.2022.306934).

COVID-19 vaccine-related presumed allergic reactions and second dose administration by using a two-step graded protocol.

Background: Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. Objectives: To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. Methods: This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Results: Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Conclusion: Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.

Evaluating the Use of an Aerosol Box During Simulated Intubations.

To evaluate the use of an aerosol box during video laryngoscopy intubation, we conducted a two-phase simulation-based study to assess if there were significant differences in time needed to safely intubate a patient with an aerosol box in place, as well as assess changes in laryngoscopists' hand motions as determined by changes in accelerometry. 20 anesthesiology providers from our institution participated in the first phase assessing the time to intubation. Use of the aerosol box led to statistically significant increases in intubation times (Wilcoxon-Signed Rank test p < 0.001, z-score = 3.921), with the calculated Pearson's correlation coefficient (r = 0.877) indicating a large effect size. An 8.5 - 11.5 second difference in median intubation times was maintained between corresponding attempts with versus without the aerosol box. 15 participants completed an optional post-assessment survey, with 10 of 15 respondents firmly stating they would not use the box in clinical practice. The hand accelerometry assessment included five anesthesiology providers from our institution. This revealed a statistically significant increase in trials with aerosol boxes for the left hand's general accelerometry with a medium effect size (p = 0.031; z = -1.873; r = -0.484), as well as for the right hand's general accelerometry with a large effect size (p < 0.001; z = -3.351; r = -0.865). Although the aerosol box is an interesting concept, its use is associated with increased time to intubation and a change in ergonomics, which may increase risk during airway management and represents a concern for patient safety.

Managing SARS-CoV-2 Testing in Schools with an Artificial Intelligence Model and Application Developed by Simulation Data

Research on SARS-CoV-2 and its social implications have become a major focus to interdisciplinary teams worldwide. As interest in more direct solutions, such as mass testing and vaccination grows, several studies appear to be dedicated to the operationalization of those solutions, leveraging both traditional and new methodologies, and, increasingly, the combination of both. This research examines the challenges anticipated for preventative testing of SARS-CoV-2 in schools and proposes an artificial intelligence (AI)-powered agent-based model crafted specifically for school scenarios. This research shows that in the absence of real data, simulation-based data can be used to develop an artificial intelligence model for the application of rapid assessment of school testing policies.

COVID-19 in pregnancy: a systematic review of chest CT findings and associated clinical features in 427 patients.

PURPOSE: Our purpose was to conduct a comprehensive systematic review of all existing literature regarding imaging findings on chest CT and associated clinical features in pregnant patients diagnosed with COVID-19. MATERIALS & METHODS: A literature search was conducted on April 21, 2020 and updated on July 24, 2020 using PubMed, Embase, World Health Organization, and Google Scholar databases. Only studies which described chest CT findings of COVID-19 in pregnant patients were included for analysis. RESULTS: A total of 67 articles and 427 pregnant patients diagnosed with COVID-19 were analyzed. The most frequently encountered pulmonary findings on chest CT were ground-glass opacities (77.2%, 250/324), posterior lung involvement (72.5%, 50/69), multilobar involvement (71.8%, 239/333), bilateral lung involvement (69.4%, 231/333), peripheral distribution (68.1%, 98/144), and consolidation (40.9%, 94/230). Pregnant patients were also found to present more frequently with consolidation (40.9% vs. 21.0-31.8%) and pleural effusion (30.0% vs. 5.0%) in comparison to the general population. Associated clinical features included antepartum fever (198 cases), lymphopenia (128 cases), and neutrophilia (97 cases). Of the 251 neonates delivered, 96.8% had negative RT-PCR and/or IgG antibody testing for COVID-19. In the eight cases (3.2%) of reported neonatal infection, tests were either conducted on samples collected up to 72 h after birth or were found negative on all subsequent RT-PCR tests. CONCLUSION: Pregnant patients appear to present more commonly with more advanced COVID-19 CT findings compared to the general adult population. Furthermore, characteristic laboratory abnormalities found in pregnant patients tended to mirror those found in the general patient population. Lastly, results from neonatal testing suggest a low risk of vertical transmission.

Drug Shortage and Critical Medication Inventory Management at a Children's Hospital During the COVID-19 Pandemic.

Drug shortages have significantly affected the ability to provide care at pediatric institutions, particularly in the inpatient and critical care settings. The coronavirus disease 2019 (COVID-19) pandemic highlighted additional challenges with drug supply chains. A working group consisting of pharmacy management, clinical pharmacists, and pharmacy buyers met regularly at the beginning of the COVID-19 pandemic. In collaboration with medical staff leadership and the Pharmacy and Therapeutics Committee, we developed a pediatric critical drug list to track essential medications for targeted monitoring. We created an inventory model with easily modifiable input variables related to patient and hospital data. This model was aligned across affiliate health care systems to increase transparency of our hospital's surge capacity for managing patients with COVID-19. Here, we share our framework for modeling drug inventory management at a freestanding children's hospital during a global pandemic.

Artificial Intelligence Model of Drive-Through Vaccination Simulation.

Planning for mass vaccination against SARS-Cov-2 is ongoing in many countries considering that vaccine will be available for the general public in the near future. Rapid mass vaccination while a pandemic is ongoing requires the use of traditional and new temporary vaccination clinics. Use of drive-through has been suggested as one of the possible effective temporary mass vaccinations among other methods. In this study, we present a machine learning model that has been developed based on a big dataset derived from 125K runs of a drive-through mass vaccination simulation tool. The results show that the model is able to reasonably well predict the key outputs of the simulation tool. Therefore, the model has been turned to an online application that can help mass vaccination planners to assess the outcomes of different types of drive-through mass vaccination facilities much faster.

Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.

BACKGROUND: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. OBJECTIVE: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. METHODS: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. RESULTS: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15). CONCLUSIONS: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.