Health Surveillance in a Down Syndrome Specialty Clinic: Implementation of Electronic Health Record Integrations During the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To address gaps in routine recommended care for children with Down syndrome, through quality improvement during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: A retrospective chart review of patients with Down syndrome was conducted. Records of visits to the Massachusetts General Hospital Down Syndrome Program were assessed for adherence to 5 components of the 2011 American Academy of Pediatrics (AAP) Clinical Report, "Health Supervision for Children with Down Syndrome." The impact of 2 major changes was analyzed using statistical process control charts: a planned intervention of integrations to the electronic health record for routine health maintenance with age-based logic based on a diagnosis of Down syndrome, created and implemented in July 2020; and a natural disruption in care due to the COVID-19 pandemic, starting in March 2020. RESULTS: From December 2018 to March 2022, 433 patients with Down syndrome had 940 visits. During the COVID-19 pandemic, adherence to the audiology component decreased (from 58% to 45%, P < .001); composite adherence decreased but later improved. Ophthalmology evaluation remained stable. Improvement in adherence to 3 components (thyroid-stimulating hormone, hemoglobin, sleep study ever) in July 2020 coincided with electronic health record integrations. Total adherence to the 5 AAP guideline components was greater for follow-up visits compared with new patient visits (69% and 61%, respectively; P < .01). CONCLUSIONS: The COVID-19 pandemic influenced adherence to components of the AAP Health supervision for children with Down syndrome, but improvements in adherence coincided with implementation of our intervention and reopening after the COVID-19 pandemic.

Risk for Severe Illness and Death among Pediatric Patients with Down Syndrome Hospitalized for COVID-19, Brazil.

Down syndrome is the most common human chromosomal disorder. Whether Down syndrome is a risk factor for severe COVID-19 outcomes in pediatric patients remains unclear, especially in low-to-middle income countries. We gathered data on patients <18 years of age with SARS-CoV-2 infection from a national registry in Brazil to assess the risk for severe outcomes among patients with Down syndrome. We included data from 14,684 hospitalized patients, 261 of whom had Down syndrome. After adjustments for sociodemographic and medical factors, patients with Down syndrome had 1.8 times higher odds of dying from COVID-19 (odds ratio 1.82, 95% CI 1.22-2.68) and 27% longer recovery times (hazard ratio 0.73, 95% CI 0.61-0.86) than patients without Down syndrome. We found Down syndrome was associated with increased risk for severe illness and death among COVID-19 patients. Guidelines for managing COVID-19 among pediatric patients with Down syndrome could improve outcomes for this population.

Risk of Severe Coronavirus Disease 2019 Disease in Individuals With Down Syndrome: A Matched Cohort Study From a Large, Integrated Health Care System.

BACKGROUND: Down syndrome (DS) is associated with an increased risk of infections attributed to immune defects. Whether individuals with DS are at an increased risk of severe coronavirus disease 2019 (COVID-19) remains unclear. METHODS: In a matched cohort study, we evaluated the risk of COVID-19 infection and severe COVID-19 disease in individuals with DS and their matched counterparts in a pre-COVID-19 vaccination period at Kaiser Permanente Southern California. Multivariable Cox proportion hazard regression was used to investigate associations between DS and risk of COVID-19 infection and severe COVID-19 disease. RESULTS: Our cohort included 2541 individuals with DS and 10 164 without DS matched on age, sex, and race/ethnicity (51.6% female, 53.3% Hispanic, median age 25 years [interquartile range, 14-38]). Although the rate of COVID-19 infection in individuals with DS was 32% lower than their matched counterparts (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], .56-.83), the rate of severe COVID-19 disease was 6-fold higher (aHR, 6.14; 95% CI, 1.87-20.16). CONCLUSIONS: Although the risk of COVID-19 infection is lower, the risk of severe disease is higher in individuals with DS compared with their matched counterparts. Better infection monitoring, early treatment, and promotion of vaccine for COVID-19 are warranted for DS populations.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries.

Clinical characteristics and comorbidities of COVID-19 in unvaccinated patients with Down syndrome: first year report in Brazil.

Patients with Down syndrome (DS) are more affected by the Coronavirus Disease (COVID)-19 pandemic when compared with other populations. Therefore, the primary aim of our study was to report the death (case fatality rate) from SARS-CoV-2 infection in Brazilian hospitalized patients with DS from 03 January 2020 to 04 April 2021. The secondary objectives were (i) to compare the features of patients with DS and positive for COVID-19 (G1) to those with DS and with a severe acute respiratory infection (SARI) from other etiological factors (G2) to tease apart the unique influence of COVID-19, and (ii) to compare the features of patients with DS and positive for COVID-19 to those without DS, but positive for COVID-19 (G3) to tease apart the unique influence of DS. We obtained the markers for demographic profile, clinical symptoms, comorbidities, and the clinical features for SARI evolution during hospitalization in the first year of the COVID-19 pandemic in Brazil from a Brazilian open-access database. The data were compared between (i) G1 [1619 (0.4%) patients] and G2 [1431 (0.4%) patients]; and between (ii) G1 and G3 [222,181 (64.8%) patients]. The case fatality rate was higher in patients with DS and COVID-19 (G1: 39.2%), followed by individuals from G2 (18.1%) and G3 (14.0%). Patients from G1, when compared to G2, were older (≥ 25 years of age), presented more clinical symptoms related to severe illness and comorbidities, needed intensive care unit (ICU) treatment and non-invasive mechanical ventilation (MV) more frequently, and presented a nearly two fold-increased chance of death (OR = 2.92 [95% CI 2.44-3.50]). Patients from G1, when compared to G3, were younger (< 24 years of age), more prone to nosocomial infection, presented an increased chance for clinical symptoms related to a more severe illness; frequently needed ICU treatment, and invasive and non-invasive MV, and raised almost a three fold-increased chance of death (OR = 3.96 [95% CI 3.60-4.41]). The high case fatality rate in G1 was associated with older age (≥ 25 years of age), presence of clinical symptoms, and comorbidities, such as obesity, related to a more severe clinical condition. Unvaccinated patients with DS affected by COVID-19 had a high case fatality rate, and these patients had a different profile for comorbidities, clinical symptoms, and treatment (such as the need for ICU and MV) when compared with other study populations.

Susceptibility to COVID-19 Diagnosis in People with Down Syndrome Compared to the General Population: Matched-Cohort Study Using Primary Care Electronic Records in the UK.

BACKGROUND: During the COVID-19 pandemic, people with Down syndrome (DS) have experienced a more severe disease course and higher mortality rates than the general population. It is not yet known whether people with DS are more susceptible to being diagnosed with COVID-19. OBJECTIVE: To explore whether DS is associated with increased susceptibility to COVID-19. DESIGN: Matched-cohort study design using anonymised primary care electronic health records from the May 2021 release of Clinical Practice Research Datalink (CPRD) Aurum. SETTING: Electronic health records from approximately 1400 general practices (GPs) in England. PARTICIPANTS: 8854 people with DS and 34,724 controls matched for age, gender and GP who were registered on or after the 29th January 2020. MEASUREMENTS: The primary outcome was COVID-19 diagnosis between January 2020 and May 2021. Conditional logistic regression models were fitted to estimate associations between DS and COVID-19 diagnosis, adjusting for comorbidities. RESULTS: Compared to controls, people with DS were more likely to be diagnosed with COVID-19 (7.4% vs 5.6%, p ≤ 0.001, odds ratio (OR) = 1.35; 95% CI = 1.23-1.48). There was a significant interaction between people with DS and a chronic respiratory disease diagnosis excluding asthma and increased odds of a COVID-19 diagnosis (OR = 1.71; 95% CI = 1.20-2.43), whilst adjusting for a number of comorbidities. CONCLUSION: Individuals with DS are at increased risk for contracting COVID-19. Those with underlying lung conditions are particularly vulnerable during viral pandemics and should be prioritised for vaccinations.

Specific Susceptibility to COVID-19 in Adults with Down Syndrome.

The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer's disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization.

Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform.

OBJECTIVE: To assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children. DESIGN: Population based cohort study on behalf of NHS England using the OpenSAFELY platform. SETTING: Patient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service. PARTICIPANTS: Adults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down's syndrome and cerebral palsy were identified (whether or not they were on the learning disability register). MAIN OUTCOME MEASURE: Covid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored. RESULTS: For wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down's syndrome and cerebral palsy were associated with increased hazards for both events; Down's syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children. CONCLUSIONS: People with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.

COVID-19 in patients with Down syndrome.

PURPOSE: The aim of the current study was to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people with Down syndrome (DS). METHODS: All consecutive patients who were admitted at healthcare facilities anywhere in Fars province (located in the south of Iran with a population of 4,851,000 people) from 19 February 2020 to 20 November 2020 were included. For every patient with DS, three age- and sex-matched patients with COVID-19 and without any underlying medical conditions were selected as controls. RESULTS: During the study period, 37,968 patients were hospitalized with a diagnosis of COVID-19. Eighteen patients had DS. Patients with DS were significantly more likely to be intubated [7 patients (39%)] compared with those without DS [3 patients (6%)]; p = 0.002. Patients with DS significantly more often died of COVID-19 compared with the controls [8 (44.4%) vs. 1 (1.9%); odds ratio: 24.37; 95% confidence interval 2.39-247.94; p = 0.007]. CONCLUSION: Patients with DS are among the high-risk populations with respect to severe COVID-19 and should receive the vaccine as soon as possible. Furthermore, they should receive more intensive care if they get hospitalized with the illness.

Down's syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach.

Down syndrome (DS) is the most common genetic cause of learning difficulties and intellectual disabilities. DS patients often present with several congenital defects and chronic diseases, including immunity disorders. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) have been seen, which appear to vary with age. At birth, patients present with combined immunodeficiency, with frequent infections that decrease with age. Furthermore, high levels of IL-4 and IL-10 with anti-inflammatory properties and low levels of IL-6 and TNF-α are described in children. The immune system is believed to play an essential role in SARS-CoV-2 pathogenesis, and it has been associated with elevated levels of pro-inflammatory cytokines and an exaggerated cytokine release syndrome (CRS) that may eventually trigger a severe situation called cytokine storm. On the other hand, genetic features seem to be involved in the predisposition to illness and its severity. Overexpression of DSCR1 and ZAKI-4 inhibits the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus, a main step in the inflammatory responsiveness. We discuss here the possible role of immunology and genetic features of DS in the infection and prognosis in COVID-19.

Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19.

SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection or poorer clinical outcomes. In order to get insight into the interplay between DS genes and SARS-cov2 infection and pathogenesis we identified the genes associated with the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We then analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) and created a DS-SARS-CoV-2 network. We detected COVID-19 protective and risk factors among HSA21 genes and interactors and/or DS deregulated genes that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome. Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells. However, as the anti-viral interferon I signaling is also upregulated in DS, this might increase the initial anti-viral response, inhibiting viral genome release, viral replication and viral assembly. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.

Transition to virtual clinic: Experience in a multidisciplinary clinic for Down syndrome.

The COVID-19 pandemic necessitated a rapid transition from in-person office visits to virtual visits in the Down syndrome specialty program at Massachusetts General Hospital (MGH DSP). We describe the clinic transition to virtual visits in April 2020 and reflect on our six-month experience in virtual visits. Clinic metrics were tracked. Electronic survey responses were collected from caregivers attending virtual visits. Input from the MGH DSP team was collected. From April to September 2020, we maintained patient volume (45 visits per month) and overall satisfaction score (6.7 out of 7) following a sudden, unanticipated transition to virtual visits. Survey of 17 caregivers attending virtual visits found that most were equipped with technology, had access to a private location, and most were able to access visit without any limitations. Caregivers appreciated the convenience of virtual visits but sometimes missed the personal connection of an in-person visit. Overall, though, virtual visits were frequently viewed as no different than office visits. Team members identified benefits and challenges of virtual visits, as well as lessons learned from this transition. We were able to maintain multidisciplinary, specialty care with optimal caregiver feedback and sustained number of patient visits.

Pneumonia and respiratory infections in Down syndrome: A scoping review of the literature.

Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty-two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID-19 pandemic.

Trisomy 21 and Coronavirus Disease 2019 in Pediatric Patients.

We present 4 pediatric patients with trisomy 21 (T21) and associated comorbidities who developed coronavirus disease 2019 requiring hospitalization. A review of the literature revealed that comorbidities associated with T21 may predispose patients to severe disease. Children with T21 should be considered high risk and monitored carefully if infected with severe acute respiratory syndrome coronavirus 2.

Clinical characteristics of individuals with Down syndrome deceased with CoVID-19 in Italy-A case series.

BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.