Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanisms.

OBJECTIVE: Cyanoacrylate glue closure was first used in humans 10 years ago to treat venous reflux of the axial veins. Studies have since shown its clinical efficacy in vein closure. However, great need exists to elucidate further the types of specific adverse reactions that cyanoacrylate glue can cause for better patient selection and to minimize these events. In the present study, we systematically reviewed the literature to identify the types of reported reactions. In addition, we explored the pathophysiology contributing to these reactions and proposed the mechanistic pathway with inclusion of actual cases. METHODS: We searched the literature for reports of reactions following cyanoacrylate glue use in patients with venous diseases between 2012 and 2022. The search was performed using MeSH (medical subject headings) terms. The terms included cyanoacrylate, venous insufficiency, chronic venous disorder, varicose veins, vein varicosities, venous ulcer, venous wound, CEAP (clinical, etiologic, anatomic, pathophysiologic), vein, adverse events, phlebitis, hypersensitivity, foreign body granuloma, giant cell, endovenous glue-induced thrombosis, and allergy. The search was limited to the literature reported in English. These studies were evaluated for the type of product used and the reactions noted. A systematic review, in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) method, was performed. Covidence software (Melbourne, VC, Australia) was used for full-text screening and data extraction. Two reviewers reviewed the data, and the content expert served as the tiebreaker. RESULTS: We identified 102, of which, 37 reported on cyanoacrylate use other than in the context of chronic venous diseases and were excluded. Fifty-five reports were determined appropriate for data extraction. The adverse reactions to cyanoacrylate glue were phlebitis, hypersensitivity, foreign body granuloma, and endovenous glue-induced thrombosis. CONCLUSIONS: Although cyanoacrylate glue closure for venous reflux is generally a safe and clinically effective treatment choice for patients with symptomatic chronic venous disease and axial reflux, some adverse events could be specific to the properties of the cyanoacrylate product. We propose mechanisms for how such reactions can occur based on histologic changes, published reports, and case examples; however, further exploration is necessary to confirm these theories.

The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. METHODS: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. FINDINGS: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. INTERPRETATION: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. FUNDING: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta.

Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Because of confounding factors in the human population, such as preexisting immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were up-regulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggest that, in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

Interventions to support the mental health and well-being of front-line healthcare workers in hospitals during pandemics: an evidence review and synthesis.

OBJECTIVE: Pandemics negatively impact healthcare workers' (HCW's) mental health and well-being causing additional feelings of anxiety, depression, moral distress and post-traumatic stress. A comprehensive review and evidence synthesis of HCW's mental health and well-being interventions through pandemics reporting mental health outcomes was conducted addressing two questions: (1) What mental health support interventions have been reported in recent pandemics, and have they been effective in improving the mental health and well-being of HCWs? (2) Have any mobile apps been designed and implemented to support HCWs' mental health and well-being during pandemics? DESIGN: A narrative evidence synthesis was conducted using Cochrane criteria for synthesising and presenting findings when systematic review and pooling data for statistical analysis are not suitable due to the heterogeneity of the studies. DATA SOURCES: Evidence summary resources, bibliographic databases, grey literature sources, clinical trial registries and protocol registries were searched. ELIGIBILITY CRITERIA: Subject heading terms and keywords covering three key concepts were searched: SARS-CoV-2 coronavirus (or similar infectious diseases) epidemics, health workforce and mental health support interventions. Searches were limited to English-language items published from 1 January 2000 to 14 June 2022. No publication-type limit was used. DATA EXTRACTION AND SYNTHESIS: Two authors determined eligibility and extracted data from identified manuscripts. Data was synthesised into tables and refined by coauthors. RESULTS: 2694 studies were identified and 27 papers were included. Interventions were directed at individuals and/or organisations and most were COVID-19 focused. Interventions had some positive impacts on HCW's mental health and well-being, but variable study quality, low sample sizes and lack of control conditions were limitations. Two mobile apps were identified with mixed outcomes. CONCLUSION: HCW interventions were rapidly designed and implemented with few comprehensively described or evaluated. Tailored interventions that respond to HCWs' needs using experience co-design for mental health and well-being are required with process and outcome evaluation.

Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine.

BACKGROUND: In late 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VoC) was reported with many mutations in the viral spike protein that were predicted to enhance transmissibility and allow viral escape of neutralizing antibodies. Within weeks of the first report of B.1.1.529, this VoC has rapidly spread throughout the world, replacing previously circulating strains of SARS-CoV-2 and leading to a resurgence in COVID-19 cases even in populations with high levels of vaccine- and infection-induced immunity. Studies have shown that B.1.1.529 is less sensitive to protective antibody conferred by previous infections and vaccines developed against earlier lineages of SARS-CoV-2. The ability of B.1.1.529 to spread even among vaccinated populations has led to a global public health demand for updated vaccines that can confer protection against B.1.1.529. METHODS: We rapidly developed a replicating RNA vaccine expressing the B.1.1.529 spike and evaluated immunogenicity in mice and hamsters. We also challenged hamsters with B.1.1.529 and evaluated whether vaccination could protect against viral shedding and replication within respiratory tissue. FINDINGS: We found that mice previously immunized with A.1-specific vaccines failed to elevate neutralizing antibody titers against B.1.1.529 following B.1.1.529-targeted boosting, suggesting pre-existing immunity may impact the efficacy of B.1.1.529-targeted boosters. Furthermore, we found that our B.1.1.529-targeted vaccine provides superior protection compared to the ancestral A.1-targeted vaccine in hamsters challenged with the B.1.1.529 VoC after a single dose of each vaccine. INTERPRETATION: Our data suggest that B.1.1.529-targeted vaccines may provide superior protection against B.1.1.529 but pre-existing immunity and timing of boosting may need to be considered for optimum protection. FUNDING: This research was supported in part by the Intramural Research Program, NIAID/NIH, Washington Research Foundation and by grants 27220140006C (JHE), AI100625, AI151698, and AI145296 (MG).

Antiviral metabolite 3'-deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19.

BACKGROUND: There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing. METHODS: Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with viral infections (including COVID-19), bacterial infections, inflammatory conditions, and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings. Associations between whole-blood gene expression and the identified metabolite of interest were examined. FINDINGS: 3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), was detected for the first time in serum. When comparing 60 viral with 101 non-viral cases in the discovery cohort, ddhC was the most significantly differentially abundant metabolite, generating an area under the receiver operating characteristic curve (AUC) of 0.954 (95% CI: 0.923-0.986). In the validation cohort, ddhC was again the most significantly differentially abundant metabolite when comparing 40 viral with 40 bacterial cases, generating an AUC of 0.81 (95% CI 0.708-0.915). Transcripts of viperin and CMPK2, enzymes responsible for ddhCTP synthesis, were among the five genes most highly correlated with ddhC abundance. CONCLUSIONS: The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and CMPK2 are implicated in ddhC production in vivo. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness, and acute infection management. FUNDING: NIHR Imperial BRC; UKRI.

Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model.

The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC), which contains a heavily mutated spike protein capable of escaping preexisting immunity, identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here, we assessed the efficacy of MK-4482 against the earlier Alpha, Beta, and Delta VOCs and Omicron in the hamster COVID-19 model. Omicron replication and associated lung disease in vehicle-treated hamsters was reduced compared with replication and lung disease associated with earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of hamsters infected with Alpha, Beta, or Delta VOCs. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious titers compared with viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants.

1H NMR Signals from Urine Excreted Protein Are a Source of Bias in Probabilistic Quotient Normalization.

Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared across a large proportion of the spectral profile (>50%). Where 1H nuclear magnetic resonance (NMR) spectroscopy is employed, the presence of urinary protein can elevate the spectral baseline and substantially impact the resulting profile. Using 1H NMR profile measurements of spot urine samples collected from hospitalized COVID-19 patients in the ISARIC 4C study, we determined that PQN coefficients are significantly correlated with observed protein levels (r2 = 0.423, p < 2.2 × 10-16). This correlation was significantly reduced (r2 = 0.163, p < 2.2 × 10-16) when using a computational method for suppression of macromolecular signals known as small molecule enhancement spectroscopy (SMolESY) for proteinic baseline removal prior to PQN. These results highlight proteinuria as a common yet overlooked source of bias in 1H NMR metabolic profiling studies which can be effectively mitigated using SMolESY or other macromolecular signal suppression methods before estimation of normalization coefficients.

Three-Week Old Pigs Are Not Susceptible to Productive Infection with SARS-COV-2.

As the COVID-19 pandemic moves into its third year, there remains a need for additional animal models better recapitulating severe COVID to study SARS-CoV-2 pathogenesis and develop countermeasures, especially treatment options. Pigs are known intermediate hosts for many viruses with zoonotic potential and are susceptible to infection with alpha, beta and delta genera of coronaviruses. Herein, we infected young (3 weeks of age) pigs with SARS-CoV-2 using a combination of respiratory and parenteral inoculation routes. Pigs did not develop clinical disease, nor macroscopic or microscopic pathologic lesions upon SARS-CoV-2 infection. Despite occasional low levels of SARS-CoV-2 genomic RNA in the respiratory tract, subgenomic RNA and infectious virus were never found, and SARS-CoV-2-specific adaptive immune responses were not detectable over the 13-day study period. We concluded that pigs are not susceptible to productive SARS-CoV-2 infection and do not serve as a SARS-CoV-2 reservoir for zoonotic transmission.

Antiviral metabolite 3'-Deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19

Mehta et al. perform untargeted metabolic profiling of serum samples from patients presenting to the emergency department with different infections. The antiviral small molecule 3’-Deoxy-3’,4’-didehydro-cytidine (ddhC) was detectable in human serum and accurately differentiated viral infections from other infection syndromes in both a discovery and validation patient cohort.

Nurturing attachments group: A virtual group intervention for adults caring for traumatised children in the context of COVID-19.

Background: Evidence indicates that the more traditional and behavioural parenting strategies are ineffective when parenting a child who has experienced developmental trauma. Recognising the need to parent with an attachment focus, the current paper evaluates the effectiveness of running the [Enfys] Nurturing Attachments Group, virtually, within the context of the COVID-19 pandemic. Method: A pilot feasibility study evaluated eight bespoke groups. Consenting professionals and co-professionals completed the Brief Parental Self-Efficacy Scale (BFSS), Care Questionnaire (CQ) and the Parental Reflective Functioning Questionnaire (PRFQ). Results: One hundred forty individuals attended the groups, with 51 (36%) completing both pre-and post-measures. The results provide evidence that professionals and co-professionals reported statistically significant positive increases on both the BPSS (d = .55) and CQ (d = .62). For the PRFQ, the results showed a statistically significant decrease on the Pre-mentalising sub scale, a non-significant mid-range score for Certainty about Mental States and a non-significant increase for Parental Interest and Curiosity in Mental States. Conclusion: The study has demonstrated initial viability of effectively facilitating the [Enfys] Nurturing Attachments Group, virtually. Importantly, it has also shown that the group can be run with professionals alongside co-professionals.

UK B.1.1.7 (Alpha) variant exhibits increased respiratory replication and shedding in nonhuman primates.

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, we compared African green monkeys infected intranasally with either the UK B.1.1.7 (Alpha) variant or its contemporary D614G progenitor. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases.

Impact of presymptomatic COVID-19 on vascular and skeletal muscle function: a case study.

The impact of COVID-19 has been largely described after symptom development. Although the SARS-CoV-2 virus elevates heart rate (HR) prior to symptom onset, whether this virus evokes other presymptomatic alterations is unknown. This case study details the presymptomatic impact of COVID-19 on vascular and skeletal muscle function in a young woman [24 yr, 173.5 cm, 89 kg, body mass index (BMI): 29.6 kg·m-2]. Vascular and skeletal muscle function were assessed as part of a separate study with the first and second visits separated by 2 wk. On the evening following the second visit, the participant developed a fever and a rapid antigen test confirmed a positive COVID-19 diagnosis. Compared with the first visit, the participant presented with a markedly elevated HR (∼30 beats/min) and a lower mean blood pressure (∼8 mmHg) at the second visit. Vascular function measured by brachial artery flow-mediated dilation, reactive hyperemia, and passive leg movement were all noticeably attenuated (25%-65%) as was leg blood flow during knee extension exercise. Muscle strength was diminished as was ADP-stimulated respiration (30%), assessed in vitro, whereas there was a 25% increase in the apparent Km. Lastly, an elevation in IL-10 was observed prior to symptom onset. Notably, 2.5 mo after diagnosis symptoms of fatigue and cough were still present. Together, these findings provide unique insight into the physiological responses immediately prior to onset of COVID-19 symptoms; they suggest that SARS-CoV-2 negatively impacts vascular and skeletal muscle function prior to the onset of common symptoms and may set the stage for the widespread sequelae observed following COVID-19 diagnosis.NEW & NOTEWORTHY This unique case study details the impact of SARS-CoV-2 infection on vascular and skeletal muscle function in a young predominantly presymptomatic woman. Prior to COVID-19 diagnosis, substantial reductions in vascular, skeletal muscle, and mitochondrial function were observed along with an elevation in IL-10. This integrative case study indicates that the presymptomatic impact of COVID-19 is widespread and may help elucidate the acute and long-term sequelae of this disease.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Rapid Design and Delivery of an Experience-Based Co-designed Mobile App to Support the Mental Health Needs of Health Care Workers Affected by the COVID-19 Pandemic: Impact Evaluation Protocol.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of health care workers' mental health and well-being for the successful function of the health care system. Few targeted digital tools exist to support the mental health of hospital-based health care workers, and none of them appear to have been led and co-designed by health care workers. OBJECTIVE: RMHive is being led and developed by health care workers using experience-based co-design (EBCD) processes as a mobile app to support the mental health challenges posed by the COVID-19 pandemic to health care workers. We present a protocol for the impact evaluation for the rapid design and delivery of the RMHive mobile app. METHODS: The impact evaluation will adopt a mixed methods design. Qualitative data from photo interviews undertaken with up to 30 health care workers and semistructured interviews conducted with up to 30 governance stakeholders will be integrated with qualitative and quantitative user analytics data and user-generated demographic and mental health data entered into the app. Analyses will address three evaluation questions related to engagement with the mobile app, implementation and integration of the app, and the impact of the app on individual mental health outcomes. The design and development will be described using the Mobile Health Evidence Reporting and Assessment guidelines. Implementation of the app will be evaluated using normalization process theory to analyze qualitative data from interviews combined with text and video analysis from the semistructured interviews. Mental health impacts will be assessed using the total score of the 4-item Patient Health Questionnaire (PHQ4) and subscale scores for the 2-item Patient Health Questionnaire for depression and the 2-item Generalized Anxiety Scale for anxiety. The PHQ4 will be completed at baseline and at 14 and 28 days. RESULTS: The anticipated average use period of the app is 30 days. The rapid design will occur over four months using EBCD to collect qualitative data and develop app content. The impact evaluation will monitor outcome data for up to 12 weeks following hospital-wide release of the minimal viable product release. The study received funding and ethics approvals in June 2020. Outcome data is expected to be available in March 2021, and the impact evaluation is expected to be published mid-2021. CONCLUSIONS: The impact evaluation will examine the rapid design, development, and implementation of the RMHive app and its impact on mental health outcomes for health care workers. Findings from the impact evaluation will provide guidance for the integration of EBCD in rapid design and implementation processes. The evaluation will also inform future development and rollout of the app to support the mental health needs of hospital-based health care workers more widely. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26168.

Impact of Coronavirus Disease 2019 (COVID-19) on Patients With Congenital Heart Disease Across the Lifespan: The Experience of an Academic Congenital Heart Disease Center in New York City.

Background We sought to assess the impact and predictors of coronavirus disease 2019 (COVID-19) infection and severity in a cohort of patients with congenital heart disease (CHD) at a large CHD center in New York City. Methods and Results We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID-19 between March 1, 2020 and July 1, 2020. The primary end point was moderate/severe response to COVID-19 infection defined as (1) death during COVID-19 infection; or (2) need for hospitalization and/or respiratory support secondary to COVID-19 infection. Among 53 COVID-19-positive patients with CHD, 10 (19%) were <18 years of age (median age 34 years of age). Thirty-one (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, 6 (11%) had pulmonary hypertension, and 9 (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, 9 (17%) had a moderate/severe infection, including 3 deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (odds ratio [OR], 35.82; P=0.0002), and in adults, physiological Stage C or D (OR, 19.38; P=0.002) were significantly associated with moderate/severe infection. Conclusions At our CHD center, the number of symptomatic patients with COVID-19 was relatively low. Patients with CHD with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection.

SARS-CoV-2 Infection in Patients with Down Syndrome, Congenital Heart Disease, and Pulmonary Hypertension: Is Down Syndrome a Risk Factor?

With increasing information available about the epidemiology, pathophysiology, and management of patients affected with severe acute respiratory syndrome corona virus-2 infection, patients with Down syndrome, congenital heart disease, airway obstruction, and pulmonary hypertension present a unique challenge. This case series describes 3 patients with Down syndrome and respiratory failure secondary to coronavirus infection.