Surveillance for SARS-CoV-2 in Norway Rats (Rattus norvegicus) from Southern Ontario

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%;n = 179), Hamilton (13.8%;n = 31), and the Greater Toronto Area (5.8%;n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%;n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass);confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70);both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

Interferon resistance of emerging SARS-CoV-2 variants.

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

Challenges to Food Charity Resilience During the COVID-19 Pandemic

The coronavirus 2019 (COVID-19) pandemic caused many significant disruptions to the food system, including the charitable food sector. Using qualitative interviewing, this research draws from the experiences of food pantry staff and volunteers during the early months of the pandemic in the greater Buffalo, New York area. Participants describe the impacts of the COVID-19 pandemic on product acquisition, distribution, and other challenges. Buffalo food charity organizations adapted to these challenges and demonstrated how diversified food supply lines, strong interorganizational relationships, and federal food assistance programs could increase food charity organizations' resilience to emergencies like pandemics in the future.Copyright © 2023 Taylor & Francis Group, LLC.

COVID-19 Vaccination Status and Operative Outcomes after Kidney Transplantation.

BACKGROUND: Kidney transplantation remains the best available treatment for end-stage renal disease. However, promoting graft longevity and preventing allosensitization requires strict adherence with a stringent immunosuppression regimen. The COVID-19 pandemic has offered new challenges for kidney transplant patients and many transplant centers are denying transplantation to unvaccinated patients. The aim of this study was to evaluate whether unvaccinated patients had inferior adherence after kidney transplantation along with a reduction in graft survival. STUDY DESIGN: Patients undergoing a deceased donor kidney transplantation at a single academic medical center from February 2021 to May 2022 were retrospectively reviewed. February 2021 was chosen as the start date for record review because it was 3 months after the first COVID-19 vaccination was authorized for emergency use. Patients were considered to be vaccinated if they received at least 1 dose of any mRNA vaccine by their transplantation date. RESULTS: Of the 301 patients who met study criteria, 234 were vaccinated and 67 were unvaccinated. Cohorts stratified by vaccination status were well matched. Younger age was an independent risk factor for nonvaccination. Interestingly, unvaccinated patients had worse postoperative adherence with a greater average number of missed postoperative clinic visits (p = 0.03) and a strong trend toward missing 3 or more postoperative clinic visits (p = 0.07). Finally, unvaccinated patients had statistically more subtherapeutic tacrolimus troughs (p = 0.01). CONCLUSIONS: Patients not vaccinated against COVID-19 had higher rate of postoperative nonadherence in key areas of immunosuppression monitoring and clinic visit attendance. Providers should be cognizant that an unvaccinated status may be a harbinger for poor adherence; therefore, stricter strategies for patient outreach are critical to ensure graft success in this vulnerable patient population.

Tocilizumab Versus Baricitinib for the Treatment of COVID-19 in Patients With Obesity.

Background: Tocilizumab and baricitinib have emerged as potential treatments for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following the findings of the Recovery Group and the results of the COV-BARRIER study. Unfortunately, there is a lack of guidance regarding the use of these agents in high-risk patients, such as those with obesity. Objective: To compare the outcomes of tocilizumab and baricitinib as potential treatments for obese patients infected with SARS-CoV-2. Methods: This was a multi-center retrospective analysis comparing outcomes of obese patients who received the standard of care plus tocilizumab or baricitinib for the treatment of SARS-CoV-2. Included patients had a BMI >30 kg/m2, needed ICU level care, and required non-invasive or invasive ventilatory support. Results: This study included 64 patients who received tocilizumab and 69 patients who received baricitinib. When examining the primary outcome, patients who received tocilizumab had a shorter duration of ventilatory support (10.0 vs 15.0 days, P = .016) than patients who received baricitinib. Our secondary outcome of in-hospital mortality was lower in the tocilizumab group as well (23.4% vs 53.6%, P < .001). Tocilizumab was also associated with a non-significant reduction in new positive blood cultures (13.0% vs 3.1%, P = .056) and new invasive fungal infection (7.3% vs 1.6%, P = .210). Conclusions: This retrospective review showed a reduced duration of ventilatory support in obese patients who received tocilizumab vs baricitinib. In the future, additional studies should be conducted to further examine and confirm these results.

Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including the selection of adaptive mutations and the emergence of new variant lineages. Here, we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate the transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with lower transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ~⅔ were plausibly introduced into these animal species from local human populations, while the remaining ~⅓ were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.

Assessing the effects of therapeutic combinations on SARS-CoV-2 infected patient outcomes: A big data approach.

BACKGROUND: The COVID-19 pandemic has demonstrated the need for efficient and comprehensive, simultaneous assessment of multiple combined novel therapies for viral infection across the range of illness severity. Randomized Controlled Trials (RCT) are the gold standard by which efficacy of therapeutic agents is demonstrated. However, they rarely are designed to assess treatment combinations across all relevant subgroups. A big data approach to analyzing real-world impacts of therapies may confirm or supplement RCT evidence to further assess effectiveness of therapeutic options for rapidly evolving diseases such as COVID-19. METHODS: Gradient Boosted Decision Tree, Deep and Convolutional Neural Network classifiers were implemented and trained on the National COVID Cohort Collaborative (N3C) data repository to predict the patients' outcome of death or discharge. Models leveraged the patients' characteristics, the severity of COVID-19 at diagnosis, and the calculated proportion of days on different treatment combinations after diagnosis as features to predict the outcome. Then, the most accurate model is utilized by eXplainable Artificial Intelligence (XAI) algorithms to provide insights about the learned treatment combination impacts on the model's final outcome prediction. RESULTS: Gradient Boosted Decision Tree classifiers present the highest prediction accuracy in identifying patient outcomes with area under the receiver operator characteristic curve of 0.90 and accuracy of 0.81 for the outcomes of death or sufficient improvement to be discharged. The resulting model predicts the treatment combinations of anticoagulants and steroids are associated with the highest probability of improvement, followed by combined anticoagulants and targeted antivirals. In contrast, monotherapies of single drugs, including use of anticoagulants without steroid or antivirals are associated with poorer outcomes. CONCLUSIONS: This machine learning model by accurately predicting the mortality provides insights about the treatment combinations associated with clinical improvement in COVID-19 patients. Analysis of the model's components suggests benefit to treatment with combination of steroids, antivirals, and anticoagulant medication. The approach also provides a framework for simultaneously evaluating multiple real-world therapeutic combinations in future research studies.

Time from Infiltrate on Chest Radiograph to Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Affects Mortality.

Venovenous extracorporeal membrane oxygenation (VV ECMO) has been used to treat severe coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome; however, patient selection criteria have evolved throughout the pandemic. In this study, we sought to determine the association of patient mortality with time from positive COVID-19 test and infiltrate on chest radiograph (x-ray) to VV ECMO cannulation. We hypothesized that an increasing duration between a positive COVID-19 test or infiltrates on chest x-ray and cannulation would be associated with increased mortality. This is a single-center retrospective chart review of COVID-19 VV ECMO patients from March 1, 2020 to July 28, 2021. Unadjusted and adjusted multivariate analyses were performed to assess for mortality differences. A total of 93 patients were included in our study. Increased time, in days, from infiltrate on chest x-ray to cannulation was associated with increased mortality in both unadjusted (5-9, P = 0.002) and adjusted regression analyses (odds ratio [OR]: 1.49, 95% CI: 1.22-1.81, P < 0.01). Time from positive test to cannulation was not found to be significant between survivors and nonsurvivors (7.5-11, P = 0.06). Time from infiltrate on chest x-ray to cannulation for VV ECMO should be considered when assessing patient candidacy. Further larger cohort and prospective studies are required.

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study.

OBJECTIVE: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months. RESULTS: As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n = 241) and -50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was -45.9% (n = 192, p = .0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%-44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%-41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. SIGNIFICANCE: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.

The Advanced Certifying Exam Simulation-Pro assessment instrument: evaluating surgical trainee examsmanship in virtual oral exams

Purpose In response to the COVID-19 pandemic, many educational activities in general surgery residency have shifted to a virtual environment, including the American Board of Surgery (ABS) Certifying Exam. Virtual exams may become the new standard. In response, we developed an evaluation instrument, the ACES-Pro, to assess surgical trainee performance with a focus on examsmanship in virtual oral board examinations. The purpose of this study was two-fold: (1) to assess the utility and validity of the evaluation instrument, and (2) to characterize the unique components of strong examsmanship in the virtual setting, which has distinct challenges when compared to in-person examsmanship. Methods We developed a 15-question evaluation instrument, the ACES-Pro, to assess oral board performance in the virtual environment. Nine attending surgeons viewed four pre-recorded oral board exam scenarios and scored examinees using this instrument. Evaluations were compared to assess for inter-rater reliability. Faculty were also surveyed about their experience using the instrument. Results Pilot evaluators found the ACES-Pro instrument easy to use and felt it appropriately captured key professionalism metrics of oral board exam performance. We found acceptable inter-rater reliability in the domains of verbal communication, non-verbal communication, and effective use of technology (Guttmann's lambda-2 were 0.796, 0.916, and 0.739, respectively). Conclusions The ACES-Pro instrument is an assessment with evidence for validity as understood by Kane's framework to evaluate multiple examsmanship domains in the virtual exam setting. Examinees must consider best practices for virtual examsmanship to perform well in this environment. Supplementary Information The online version contains supplementary material available at 10.1007/s44186-023-00107-7.

COVID-19 Mortality and Progress Toward Vaccinating Older Adults - World Health Organization, Worldwide, 2020-2022.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.† WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief§ prioritized vaccination of populations at increased risk, including older adults,¶ with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative.

BACKGROUND: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. METHODS: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. RESULTS: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. CONCLUSIONS: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

An ordinal severity scale for COVID-19 retrospective studies using Electronic Health Record data.

Objectives: Although the World Health Organization (WHO) Clinical Progression Scale for COVID-19 is useful in prospective clinical trials, it cannot be effectively used with retrospective Electronic Health Record (EHR) datasets. Modifying the existing WHO Clinical Progression Scale, we developed an ordinal severity scale (OS) and assessed its usefulness in the analyses of COVID-19 patient outcomes using retrospective EHR data. Materials and Methods: An OS was developed to assign COVID-19 disease severity using the Observational Medical Outcomes Partnership common data model within the National COVID Cohort Collaborative (N3C) data enclave. We then evaluated usefulness of the developed OS using heterogenous EHR data from January 2020 to October 2021 submitted to N3C by 63 healthcare organizations across the United States. Principal component analysis (PCA) was employed to characterize changes in disease severity among patients during the 28-day period following COVID-19 diagnosis. Results: The data set used in this analysis consists of 2 880 456 patients. PCA of the day-to-day variation in OS levels over the totality of the 28-day period revealed contrasting patterns of variation in disease severity within the first and second 14 days and illustrated the importance of evaluation over the full 28-day period. Discussion: An OS with well-defined, robust features, based on discrete EHR data elements, is useful for assessments of COVID-19 patient outcomes, providing insights on the progression of COVID-19 disease severity over time. Conclusions: The OS provides a framework that can facilitate better understanding of the course of acute COVID-19, informing clinical decision-making and resource allocation.

Effects of COVID-19 on Intravitreal Injection Clinic After Lockdown.

Purpose: To examine the return of patients to intravitreal injection clinic after the COVID-19 lockdown. Patients and Methods: The electronic medical records of all patients who received intravitreal injections at a tertiary care Veterans Health Administration (VHA) clinic 14 weeks post-lockdown (5/9/20-8/13/20) in Los Angeles County were reviewed. Reference groups included injection patients during the 7-week COVID-19 lockdown (3/19/20-5/8/20) and a 7-week pre-pandemic period in 2019 (3/19/19-5/8/19). Clinic volume was compared using a one-way ANOVA. Demographic data, medical and psychiatric co-morbidities, injection diagnoses, visual acuities, and clinic volumes were compared between the 3 periods using a generalized estimating equation multivariate analysis. Results: The post-lockdown period group averaged 25.1 visits per week, compared with 12.3/week during lockdown and 25.4/week pre-COVID in intravitreal injection clinic. In the post-lockdown period, the VHA injection clinic returned closer to the pre-lockdown volume compared to the VHA comprehensive clinic (98.9% vs 57.4%, p < 0.001). Post-lockdown, COPD patients and organ transplant patients were less likely to receive injections compared to 2019 (OR 0.76 p = 0.008, OR 1.37 p < 0.0001, respectively). Patients with a diagnosis of cancer increased in proportion between the pre-pandemic and the post-lockdown periods (OR 1.31, p = 0.007). No differences were found, according to psychiatric co-morbidities. After lockdown, the proportion of patients receiving injections for diabetic macular edema (DME) increased (OR 1.11, p = 0.01). Conclusion: Injection volume returned to pre-pandemic levels immediately after lockdown ended. However, patients with high-risk comorbidities did not return to intravitreal injection clinic post-lockdown. These results can inform medical organizations, which groups may need increased safety measures and targeted outreach to address their ophthalmic needs.

If You Build It, Will They Come? Is Test Site Availability a Root Cause of Geographic Disparities in COVID-19 Testing?

Objectives The purpose of this study was to examine the relationship between test site availability and testing rate within the context of social determinants of health. Study Design A retrospective ecological investigation was conducted using statewide COVID-19 testing data between March 2020 and December 2021. Methods Ordinary least squares and geographically weighted regression were used to estimate state and zip code level associations between testing rate and testing sites per capita, adjusting for neighbourhood level confounders. Results Findings indicate that site availability is positively associated with the zip code level testing rate and that this association is amplified in communities of greater economic deprivation. Additionally, economic deprivation is a key factor for consideration when examining ethnic differences in testing in medically underserved states. Conclusion The study findings could be used to guide delivery of testing facilities in resource-constrained states.

Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer.

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices.