Epidemiology of Neonatal COVID-19 in the United States.

OBJECTIVES: Data on coronavirus disease 2019 (COVID-19) infections in neonates are limited. We aimed to identify and describe the incidence, presentation, and clinical outcomes of neonatal COVID-19. METHODS: Over 1 million neonatal encounters at 109 United States health systems, from March 2020 to February 2021, were extracted from the Cerner Real World Database. COVID-19 diagnosis was assessed using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) laboratory tests and diagnosis codes. Incidence of COVID-19 per 100 000 encounters was estimated. RESULTS: COVID-19 was diagnosed in 918 (0.1%) neonates (91.1 per 100 000 encounters [95% confidence interval 85.3-97.2]). Of these, 71 (7.7%) had severe infection (7 per 100 000 [95% confidence interval 5.5-8.9]). Median time to diagnosis was 14.5 days from birth (interquartile range 3.1-24.2). Common signs of infection were tachypnea and fever. Those with severe infection were more likely to receive respiratory support (50.7% vs 5.2%, P < .001). Severely ill neonates received analgesia (38%), antibiotics (33.8%), anticoagulants (32.4%), corticosteroids (26.8%), remdesivir (2.8%), and COVID-19 convalescent plasma (1.4%). A total of 93.6% neonates were discharged home after care, 1.1% were transferred to another hospital, and discharge disposition was unknown for 5.2%. One neonate (0.1%) with presentation suggestive of multisystem inflammatory syndrome in children died after 11 days of hospitalization. CONCLUSIONS: Most neonates infected with SARS-CoV-2 were asymptomatic or developed mild illness without need for respiratory support. Some had severe illness requiring treatment of COVID-19 with remdesivir and COVID-19 convalescent plasma. SARS-CoV-2 infection in neonates, though rare, may result in severe disease.

Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US.

Importance: Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment. Objective: To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients. Design, Setting, and Participants: This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021. Exposures: Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2). Main Outcomes and Measures: The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure. Results: The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years. Conclusions and Relevance: The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.

Cerner real-world data (CRWD) - A de-identified multicenter electronic health records database.

Cerner Real-World Data TM (CRWD) is a de-identified big data source of multicenter electronic health records. Cerner Corporation secured appropriate data use agreements and permissions from more than 100 health systems in the United States contributing to the database as of March 2022. A subset of the database was extracted to include data from only patients with SARS-CoV-2 infections and is referred to as the Cerner COVID-19 Dataset. The December 2021 version of CRWD consists of 100 million patients and 1.5 billion encounters across all care settings. There are 2.3 billion, 2.9 billion, 486 million, and 11.5 billion records in the condition, medication, procedure, and lab (laboratory test) tables respectively. The 2021 Q3 COVID-19 Dataset consists of 130.1 million encounters from 3.8 million patients. The size and longitudinal nature of CRWD can be leveraged for advanced analytics and artificial intelligence in medical research across all specialties and is a rich source of novel discoveries on a wide range of conditions including but not limited to COVID-19.

Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.

BACKGROUND: Therapies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its life-threatening respiratory infection coronavirus disease 2019 (COVID-19) have been evaluated, including COVID-19 convalescent plasma (CCP). Multiple large reports of CCP treatment in adults exist. Pediatric data on CCP safety and efficacy are limited. METHODS: Single-center prospective, open-label trial looking at safety, antibody kinetics and outcomes of CCP (10 mL/kg, max 1 unit) treatment for COVID-19 in hospitalized pediatric patients with moderate to severe disease or at high-risk for serious illness. RESULTS: Thirteen patients were enrolled. No infusion-related adverse events occurred. No hematologic or metabolic adverse events were noted during hospitalization or at 3-weeks. Ten patients had clinical improvement by day 7 (WHO eight-category ordinal severity scale for COVID-19). Following CCP, anti-SARS-CoV-2 anti-nucleocapsid IgG increased significantly at 24 hours and high levels were sustained at 7- and 21-days. Transient IgM response was noted. Twelve patients (92.3%) were discharged home, 9 (75%) by day 7 post-CCP. One remained on invasive ventilatory support 42 days after CCP and was eventually discharged to an intermediate care facility. The single patient death was retrospectively confirmed to have had brain death before CCP. CONCLUSION: CCP was well tolerated in pediatric patients, resulted in rapid antibody increase, and did not appear to interfere with immune responses measured at 21 days. More pediatric data are necessary to establish the efficacy of CCP, but our data suggest benefit in moderate to severe COVID-19 when used early. Other immunologic or antiviral interventions may be added as supported by emerging data.

Long-term effects of malnutrition on severity of COVID-19.

The COVID-19 pandemic is a public health crisis that has the potential to exacerbate worldwide malnutrition. This study examines whether patients with a history of malnutrition are predisposed to severe COVID-19. To do so, data on 103,099 COVID-19 inpatient encounters from 56 hospitals in the United States between March 2020 and June 2020 were retrieved from the Cerner COVID-19 Dataset. Patients with a history of malnutrition between 2015 and 2019 were identified, and a random intercept logistic regression models for pediatric and adult patients were built controlling for patient demographics, socioeconomic status, admission vital signs, and related comorbidities. Statistical interactions between malnutrition and patient age were significant in both the pediatric [log-odds and 95% confidence interval: 0.094 (0.012, 0.175)] and adult [- 0.014 (- 0.021, - 0.006] models. These interactions, together with the main effect terms of malnutrition and age, imply higher odds for severe COVID-19 for children between 6 and 17 years with history of malnutrition. Even higher odds of severe COVID-19 exist for adults (with history of malnutrition) between 18 and 79 years. These results indicate that the long-term effect of malnutrition predisposes patients to severe COVID-19 in an age-dependent way.

Evaluating the impact of coronavirus disease 2019 on asthma morbidity: A comprehensive analysis of potential influencing factors.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic period is experiencing better asthma control, fewer exacerbations, and health care utilization, with limited data on factors that could explain this phenomenon. OBJECTIVE: To confirm these improved asthma outcomes during COVID-19 and evaluate potential contributing factors. METHODS: In 18,912 pediatric patients with asthma treated in the Children's Hospital of Orange County network from 2017 to 2020, monthly asthma-related encounters and medication summaries were extracted from electronic health records, particulate matter 2.5 (PM2.5) air pollution from the California Air Resources Board, and influenza-like illness from Illness Surveillance Network for the first 6 months of each year. Changes in outcomes between January to March and April to June (post-COVID-19 shutdown in 2020) were compared with historical data using generalized estimating equations analyses for patient outcomes and generalized linear models for pollution exceedance, influenza-positive, and telehealth visit rates. RESULTS: During COVID-19, we found 78%, 90%, 68% reductions in hospitalization, emergency department visits, and exacerbations, respectively, compared with pre-COVID-19 2020, with significantly greater changes than the same time period of 2017 to 2019 and significant reductions in albuterol and inhaled corticosteroid use (P < .05). Emergency department visit reduction was not seen for African Americans. The PM2.5 and influenza rates were also significantly reduced during COVID-19 (P < .05). Increased rates in telehealth visits were greater in the publicly insured group when compared with commercially insured. CONCLUSION: Our data confirm reduced health care utilization and suggest better asthma control during COVID-19, except for African Americans. This was associated with a significant increase in telehealth visits and reductions in PM2.5 and influenza infections, but not better asthma controller adherence.

A super learner ensemble of 14 statistical learning models for predicting COVID-19 severity among patients with cardiovascular conditions.

BACKGROUND: Cardiovascular and other circulatory system diseases have been implicated in the severity of COVID-19 in adults. This study provides a super learner ensemble of models for predicting COVID-19 severity among these patients. METHOD: The COVID-19 Dataset of the Cerner Real-World Data was used for this study. Data on adult patients (18 years or older) with cardiovascular diseases between 2017 and 2019 were retrieved and a total of 13 of these conditions were identified. Among these patients, 33,042 admitted with positive diagnoses for COVID-19 between March 2020 and June 2020 (from 59 hospitals) were identified and selected for this study. A total of 14 statistical and machine learning models were developed and combined into a more powerful super learning model for predicting COVID-19 severity on admission to the hospital. RESULT: LASSO regression, a full extreme gradient boosting model with tree depth of 2, and a full logistic regression model were the most predictive with cross-validated AUROCs of 0.7964, 0.7961, and 0.7958 respectively. The resulting super learner ensemble model had a cross validated AUROC of 0.8006 (range: 0.7814, 0.8163). The unbiased AUROC of the super learner model on an independent test set was 0.8057 (95% CI: 0.7954, 0.8159). CONCLUSION: Highly predictive models can be built to predict COVID-19 severity of patients with cardiovascular and other circulatory conditions. Super learning ensembles will improve individual and classical ensemble models significantly.

Agile clinical research: A data science approach to scrumban in clinical medicine.

The COVID-19 pandemic has required greater minute-to-minute urgency of patient treatment in Intensive Care Units (ICUs), rendering the use of Randomized Controlled Trials (RCTs) too slow to be effective for treatment discovery. There is a need for agility in clinical research, and the use of data science to develop predictive models for patient treatment is a potential solution. However, rapidly developing predictive models in healthcare is challenging given the complexity of healthcare problems and the lack of regular interaction between data scientists and physicians. Data scientists can spend significant time working in isolation to build predictive models that may not be useful in clinical environments. We propose the use of an agile data science framework based on the Scrumban framework used in software development. Scrumban is an iterative framework, where in each iteration larger problems are broken down into simple do-able tasks for data scientists and physicians. The two sides collaborate closely in formulating clinical questions and developing and deploying predictive models into clinical settings. Physicians can provide feedback or new hypotheses given the performance of the model, and refinement of the model or clinical questions can take place in the next iteration. The rapid development of predictive models can now be achieved with increasing numbers of publicly available healthcare datasets and easily accessible cloud-based data science tools. What is truly needed are data scientist and physician partnerships ensuring close collaboration between the two sides in using these tools to develop clinically useful predictive models to meet the demands of the COVID-19 healthcare landscape.