Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

BACKGROUND: The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing. METHODS: Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences. RESULTS: MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. CONCLUSIONS: We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens.

Acid-Dependent Charge Transport in a Solution-Processed 2D Conductive Metal-Organic Framework.

The development of conductive metal-organic frameworks (MOFs) presents a unique challenge in materials chemistry because it is unclear how to dope them. Here, we demonstrate that the inclusion of pendant amines on hexahydroxytriphenylene linkages results in two-dimensional (2D) polycrystalline frameworks Cu3(HHTATP)2, isostructural to its Cu3(HHTP)2 parent, and exhibits the highest electrical conductivity of 1.21 S/cm among 2D MOFs featuring CuO4 metal nodes. Moreover, the bulk material can be treated with acid, resulting in a protonation-dependent increase in the conductivity. By spin-coating the acidic solution, we fabricated large-area thin films and collectively demonstrated an intuitive route to solution-processable, dopable, conductive MOFs.

Newly Recognized Spotted Fever Group Rickettsia as Cause of Severe Rocky Mountain Spotted Fever-Like Illness, Northern California, USA.

The incidence of spotted fever group (SFG) rickettsioses in the United States has tripled since 2010. Rocky Mountain spotted fever, the most severe SFG rickettsiosis, is caused by Rickettsia rickettsii. The lack of species-specific confirmatory testing obfuscates the relative contribution of R. rickettsii and other SFG Rickettsia to this increase. We report a newly recognized rickettsial pathogen, Rickettsia sp. CA6269, as the cause of severe Rocky Mountain spotted fever-like illness in 2 case-patients residing in northern California. Multilocus sequence typing supported the recognition of this pathogen as a novel Rickettsia genotype most closely related to R. rickettsii. Cross-reactivity observed for an established molecular diagnostic test indicated that Rickettsia sp. CA6269 might be misidentified as R. rickettsii. We developed a Rickettsia sp. CA6269-specific real-time PCR to help resolve this diagnostic challenge and better characterize the spectrum of clinical disease and ecologic epidemiology of this pathogen.

Association of procurement technique with organ yield and cost following donation after circulatory death.

Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.

Intake of Blueberries, Anthocyanins, and Risk of Eye Disease in Women.

BACKGROUND: Blueberries and anthocyanins, their key bioactive component, may improve eye health. However, few long-term studies have examined blueberries and anthocyanins with cataract and age-related macular degeneration (AMD). OBJECTIVES: To investigate the prospective association between blueberry and anthocyanin intake with incident cataract, total AMD, and visually significant AMD among middle-aged and older women. METHODS: A total of 36,653 and 35,402 women initially free of AMD and cataract, respectively, aged ≥45 y from the Women's Health Study provided semiquantitative food frequency questionnaire data on blueberry intake categorized as none, 1-3 servings/mo, 1 serving/wk, or ≥2 servings/wk, plus a combined category of ≥1 serving/wk. Total anthocyanin intake and major subclasses were energy-adjusted and categorized into quintiles. Self-reported risk factors of eye disease were adjusted in multivariable hazard ratios (HRs) (95% confidence intervals [CIs]) of confirmed cataract, AMD, and visually significant AMD with mean follow-up of 11 y. RESULTS: Among the participants, 10.5% consumed ≥1 serving/wk of blueberries, with mean total anthocyanin intake of 11.2 mg/d. Compared to no blueberry intake, women consuming 1-3 servings/mo, 1 serving/wk, and ≥2 servings/wk had corresponding multivariable HRs of total AMD of 0.90 (95% CI: 0.73, 1.11), 0.71 (95% CI: 0.50, 1.00), and 0.36 (95% CI: 0.14, 0.93) (Ptrend = 0.011); those consuming ≥1 servings/wk had an HR of 0.68 (95% CI: 0.47, 0.98). A similar magnitude of HRs were found for visually significant AMD (Ptrend = 0.012) but not for cataract. There were no significant associations between increasing total anthocyanin quintiles and total and visually significant AMD, but there was a modest inverse association with cataract (Ptrend = 0.022), driven by a 10% reduction in cataract in the upper 2 quintiles. CONCLUSIONS: Greater blueberry intake significantly reduced total AMD, but not visually significant AMD or cataract. However, the magnitude of effect for visually significant AMD was similar to total AMD. There was a modest but significant inverse association between dietary anthocyanin intake with cataract but not AMD.

Modeling the human placenta: in vitro applications in developmental and reproductive toxicology.

During its temporary tenure, the placenta has extensive and specialized functions that are critical for pre- and post-natal development. The consequences of chemical exposure in utero can have profound effects on the structure and function of pregnancy-associated tissues and the life-long health of the birthing person and their offspring. However, the toxicological importance and critical functions of the placenta to embryonic and fetal development and maturation have been understudied. This narrative will review early placental development in humans and highlight some in vitro models currently in use that are or can be applied to better understand placental processes underlying developmental toxicity due to in utero environmental exposures.

Outbreak of Human Trichinellosis - Arizona, Minnesota, and South Dakota, 2022.

Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with Trichinella spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat. In July 2022, a hospitalized patient with suspected trichinellosis was reported to the Minnesota Department of Health. One week before symptom onset, the patient and eight other persons shared a meal that included bear meat that had been frozen for 45 days before being grilled and served rare with vegetables that had been cooked with the meat. Investigation identified six trichinellosis cases, including two in persons who consumed only the vegetables. Motile Trichinella larvae were found in remaining bear meat that had been frozen for >15 weeks. Molecular testing identified larvae from the bear meat as Trichinella nativa, a freeze-resistant species. Persons who consume meat from wild game animals should be aware that that adequate cooking is the only reliable way to kill Trichinella parasites and that infected meat can cross-contaminate other foods.

Gaps in diagnosing suspected infection in immunocompromised children with cancer: A systematic review.

While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement, and spanned multiple bibliographic databases and other public sources from January 1, 2012 to June 23, 2022. From 5188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients, and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.

Targeted de novo phasing and long-range assembly by template mutagenesis.

Short-read sequencers provide highly accurate reads at very low cost. Unfortunately, short reads are often inadequate for important applications such as assembly in complex regions or phasing across distant heterozygous sites. In this study, we describe novel bench protocols and algorithms to obtain haplotype-phased sequence assemblies with ultra-low error for regions 10 kb and longer using short reads only. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ∼50% of cytosines to uracils. Sequencing libraries are made from both mutated and unmutated templates. Using de Bruijn graphs and paired-end read information, we assemble each mutated template and use the unmutated library to correct the mutated bases. Templates are partitioned into two or more haplotypes, and the final haplotypes are assembled and corrected for residual template mutations and PCR errors. With sufficient template coverage, the final assemblies have per-base error rates below 10-9. We demonstrate this method on a four-member nuclear family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.

Pediatric hidradenitis suppurativa publication trends: 2012 to 2022.

There is a paucity of bibliometric data on pediatric-focused hidradenitis suppurativa (HS) publications. To better characterize research trends in pediatric HS and gaps in literature, we systematically searched PubMed between 2012 and 2022 for publications on pediatric HS and collected data on study design, topic, country, and level of evidence. Of 109 articles that met inclusion criteria, less than half (44/109, 40.4%) were high level of evidence studies; the most common study types were case reports/series (41/109, 37.6%) and cross-sectional studies (25/109, 22.9%), and the most common study topics were HS treatments (44/109, 40.4%), comorbidities (20/109, 18.3%), and clinical presentation (14/109, 12.8%). Although there has been expansion of the pediatric HS literature in recent years, our study highlights the need for larger prospective studies and trials to improve our ability to optimally manage pediatric HS patients and identify predictors of disease progression and treatment response.

Borrelia miyamotoi Infection in Immunocompromised Man, California, USA, 2021.

Infection with Borrelia miyamotoi in California, USA, has been suggested by serologic studies. We diagnosed B. miyamotoi infection in an immunocompromised man in California. Diagnosis was aided by plasma microbial cell-free DNA sequencing. We conclude that the infection was acquired in California.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Copolymerization of single-cell nucleic acids into balls of acrylamide gel.

We show the use of 5'-Acrydite oligonucleotides to copolymerize single-cell DNA or RNA into balls of acrylamide gel (BAGs). Combining this step with split-and-pool techniques for creating barcodes yields a method with advantages in cost and scalability, depth of coverage, ease of operation, minimal cross-contamination, and efficient use of samples. We perform DNA copy number profiling on mixtures of cell lines, nuclei from frozen prostate tumors, and biopsy washes. As applied to RNA, the method has high capture efficiency of transcripts and sufficient consistency to clearly distinguish the expression patterns of cell lines and individual nuclei from neurons dissected from the mouse brain. By using varietal tags (UMIs) to achieve sequence error correction, we show extremely low levels of cross-contamination by tracking source-specific SNVs. The method is readily modifiable, and we will discuss its adaptability and diverse applications.

Plasma Microbial Cell-Free DNA Sequencing from over 15,000 Patients Identified a Broad Spectrum of Pathogens.

Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection and quantification from plasma. The Karius Test, a commercial mcfDNA sequencing assay developed by and available since 2017 from Karius, Inc. (Redwood City, CA), detects and quantifies mcfDNA as molecules/µL in plasma. The commercial sample data and results for all tests conducted from April 2018 through mid-September 2021 were evaluated for laboratory quality metrics, reported pathogens, and data from test requisition forms. A total of 18,690 reports were generated from 15,165 patients in a hospital setting among 39 states and the District of Columbia. The median time from sample receipt to reported result was 26 h (interquartile range [IQR] 25 to 28), and 96% of samples had valid test results. Almost two-thirds (65%) of patients were adults, and 29% at the time of diagnostic testing had ICD-10 codes representing a diverse array of clinical scenarios. There were 10,752 (58%) reports that yielded at least one taxon for a total of 22,792 detections spanning 701 unique microbial taxa. The 50 most common taxa detected included 36 bacteria, 9 viruses, and 5 fungi. Opportunistic fungi (374 Aspergillus spp., 258 Pneumocystis jirovecii, 196 Mucorales, and 33 dematiaceous fungi) comprised 861 (4%) of all detections. Additional diagnostically challenging pathogens (247 zoonotic and vector-borne pathogens, 144 Mycobacterium spp., 80 Legionella spp., 78 systemic dimorphic fungi, 69 Nocardia spp., and 57 protozoan parasites) comprised 675 (3%) of all detections. This is the largest reported cohort of patients tested using plasma mcfDNA sequencing and represents the first report of a clinical grade metagenomic test performed at scale. Data reveal new insights into the breadth and complexity of potential pathogens identified.

Patient Perspectives on Hidradenitis Suppurativa and Infertility: A Survey Study.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition which predominantly affects women of childbearing age in the USA. There is a lack of research on the association between HS and fertility. OBJECTIVES: The aim of this study was to understand the perspectives of females with HS regarding the impact of their disease on reproductive health, the impact of fertility treatments on HS, and the impact of HS treatments on fertility. METHODS: An anonymous, online survey was disseminated through HS support groups from June to July 2022. Respondents aged 18-50 who were assigned female sex at birth were eligible for participation. Comparative statistics were performed using t tests/χ2 tests to assess associations between respondents' demographics and survey responses. RESULTS: Among the 312 respondents (80.8% White, mean age 35.7 ± 7.4 [range 18-50]), two-thirds of respondents (66.6%, 207/311) had been pregnant before and 79.5% (248/312) had ever tried to conceive. 41.5% (103/248) had unsuccessfully tried to conceive for 12 months or more. Of the 59 respondents who had never attempted to conceive, 39% reported that HS had impacted this decision. Amongst respondents who experienced fertility challenges but did not pursue fertility treatments, top barriers to fertility treatments include concerns about financial support/insurance coverage (47.5%, 29/61) and fertility treatments worsening HS (21.3%, 13/61). Most respondents who used fertility treatments reported either no change (73.7%, 28/38 or 77.8%, 14/18) or improvement (15.8%, 6/38 or 11.1%, 2/18) in their HS symptoms with oral or injectable medications. Respondents were most concerned about the effects of oral antibiotics (44.9%, 140/312), followed by hormonal medications (38.8%, 121/312) and biologics (35.9%, 112/312) on fertility. CONCLUSION: Females with HS reported high rates of infertility compared to the general population. The majority reported no change in HS symptoms with fertility treatments, and clinicians can use this finding to help counsel patients during family planning discussions. Further research in the field of HS and fertility is needed.

The improving Medication Adherence in Adolescents and young adults following Liver Transplantation (iMALT) multisite trial: Design and trial implementation considerations.

BACKGROUND/AIMS: Medication non-adherence is a leading cause of transplant rejection, organ loss, and death; yet no rigorous controlled study to date has shown compelling clinical benefits from an adherence-improving intervention. Non-adherent patients are less likely to participate in trials, and therefore, most studies enroll a majority of adherent patients who do not stand to benefit from the intervention, as they do not have the condition (non-adherence) under investigation. The improving Medication Adherence in adolescent Liver Transplant recipients trial specifically targets non-adherent patients to investigate whether a remote intervention to improve adherence results in reduced incidence of biopsy-confirmed rejection. METHODS: Improving Medication Adherence in adolescent Liver Transplant is a randomized single-blind controlled multisite, multinational National Institutes of Health-funded trial involving 13 pediatric transplant centers in the United States and Canada. An innovative, objective adherence biomarker-the Medication Level Variability Index, which is the standard deviation of a series of medication blood levels for each patient, is used to identify non-adherent patients at risk for rejection. The index is computed using electronic health record information for all potentially eligible patients based on repeated reviews of the entire clinic's roster. Identified patients, after consent, are randomized to intervention versus control (treatment as usual) arms. The remote intervention is delivered for 2 years by trained interventionists who reside in various locations in the United States. The primary outcome is the incidence of biopsy-confirmed acute cellular rejection, as confirmed by a majority vote of three pathologists who are masked to the study allocation and clinical information. DISCUSSION: Improving Medication Adherence in adolescent Liver Transplant includes several innovative design elements. The use of a validated, objective adherence index to survey a large cohort of transplant recipients allows the teams to avoid bias inherent in both convenience sampling and referral-based recruitment and enroll only patients whose computed index indicates substantially increased risk of rejection. The remote intervention paradigm helps to engage patients who are by definition hard to engage. The use of an objective, masked medical (rather than behavioral) outcome measure reduces the likelihood of biases related to clinical information and ensures broad acceptance by the field. Finally, monitoring for potential adverse events related to increased medication exposure due to the adherence intervention acknowledges that a successful intervention (increasing adherence) could have detrimental side effects via increased exposure to and potential toxicity of the medication. Such monitoring is almost never attempted in clinical trials evaluating adherence interventions.

Programming "Atomic Substitution" in Alloy Colloidal Crystals Using DNA.

Although examples of colloidal crystal analogues to metal alloys have been reported, general routes for preparing 3D analogues to random substitutional alloys do not exist. Here, we use the programmability of DNA (length and sequence) to match nanoparticle component sizes, define parent lattice symmetry and substitutional order, and achieve faceted crystal habits. We synthesized substitutional alloy colloidal crystals with either ordered or random arrangements of two components (Au and Fe3O4 nanoparticles) within an otherwise identical parent lattice and crystal habit, confirmed via scanning electron microscopy and small-angle X-ray scattering. Energy dispersive X-ray spectroscopy reveals information regarding composition and local order, while the magnetic properties of Fe3O4 nanoparticles can direct different structural outcomes for different alloys in an applied magnetic field. This work constitutes a platform for independently defining substitution within multicomponent colloidal crystals, a capability that will expand the scope of functional materials that can be realized through programmable assembly.

Chemical Vapor Deposition of Edge-on Oriented 2D Conductive Metal-Organic Framework Thin Films.

We demonstrated the synthesis of a conductive two-dimensional metal-organic framework (MOF) thin film by single-step all-vapor-phase chemical vapor deposition (CVD). The synthesized large-area thin film of Cu3(C6O6)2 has an edge-on-orientation with high crystallinity. Cu3(C6O6)2 thin film-based microdevices were fabricated by e-beam lithography and had an electrical conductivity of 92.95 S/cm. Synthesis of conductive MOF thin films by the all-vapor-phase CVD will enable fundamental studies of physical properties and may help to accomplish practical applications of conductive MOFs.

Posttraumatic stress and medication adherence in pediatric transplant recipients.

Adolescent transplant recipients may encounter a range of potentially traumatic events (PTEs) pre- and posttransplant, yet little is known about the relationship between posttraumatic stress symptoms (PTSS) and medication adherence in this population. In the present study, adolescent recipients and caregivers completed psychosocial questionnaires at enrollment. Outpatient tacrolimus trough level data were collected over 1 year to calculate the Medication Level Variability Index (MLVI), a measure of medication adherence. Nonadherence (MLVI ≥2) was identified in 34.8% of patients, and most (80.7%) reported ≥1 PTE exposure. Levels of PTSS indicating likely posttraumatic stress disorder (PTSD) were endorsed by 9.2% of patients and 43.7% of caregivers. PTSS and MLVI were significantly correlated in the liver subgroup (r = .30, p = .04). Hierarchical multivariable linear regression analyses revealed overall patient PTSS were significantly associated with QoL (p < .001). PTEs are common in adolescent recipients; a minority may meet criteria for PTSD. PTSS screening to identify nonadherence risk requires further investigation and addressing PTSS may improve QoL. Caregivers appear at greater risk for PTSD and may require their own supports. The study was approved by each participating center's Institutional Review Board.

Extracorporeal membrane oxygenation for COVID-19: An evolving experience through multiple waves.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has shown variable results in COVID-19 pneumonia however, some evidence supports benefit. Here we compare our institution's ECMO outcomes across multiple waves of the COVID-19 pandemic. METHODS: All patients who received ECMO for COVID-19 between March 1, 2020, and March 1, 2021, were reviewed. Patients received venovenous (VV) or right ventricular assist device (RVAD/ECMO) ECMO. Early (March 1-July 6, 2020, Era 1) and late (July 7, 2020-March 1, 2021, Era 2) pandemic RVAD/ECMO patients were compared. RESULTS: Fifty-four patients received ECMO of which 16 (29.6%) patients received VV ECMO and 38 (70.4%) RVAD/ECMO. Median age was 53.0 years, body mass index 36.1 kg/m2 , 41.2% female, and 49% Caucasian. The most common pre-cannulation treatments included steroids (79.6%) and convalescent plasma (70.4%). Median time from admission to cannulation was 7.0 days. Median support time was 30.5 days (VV ECMO 35.0 days, RVAD/ECMO 26.0 days). In- hospital mortality was 42.6% (39.5% RVAD/ECMO, 50.0% VV ECMO). Significant morbidities included infection (80.8%), bleeding events (74.5%), and renal replacement therapy (30.8%). Cumulative mortality 120-days post-cannulation was 45.7% (VV ECMO 60.8%, RVAD/ECMO 40.0%). RVAD/ECMO Era 1 demonstrated a significantly lower cumulative mortality (16.2%) compared to Era 2 (60.4%). Competing risk analysis found age (HR 0.95, [95% CI 0.92, 0.98] p = 0.005) to be a protective factor for survival. CONCLUSION: ECMO support for COVID-19 is beneficial but carries significant morbidity. RVAD/ECMO support demonstrated consistent advantages in survival to VV-ECMO, but with declining efficacy across time during the COVID-19 pandemic.