Hospital and ICU Admission Risk Associated With Comorbidities Among Children With COVID-19 Ancestral Strains.

A large proportion of children have been affected by COVID-19; we evaluated the association between comorbidities and hospitalization/ICU (intensive care unit) admission among 4097 children under age 21 years with symptomatic COVID-19 (not just polymerase chain reaction [PCR]-positive or multisystem inflammatory syndrome in children associated with COVID-19 [MIS-C]) from 2 large health systems from March 2020 to September 2021. Significant comorbidities and demographic factors identified by univariable analysis were included in a multivariable logistic regression compared with children ages 6 to 11 without comorbidities. In all, 475 children (11.6%) were hospitalized, of whom 25.5% required ICU admission. Children under 1 year had high hospitalization risk, but low risk of ICU admission. Presence of at least 1 comorbidity was associated with hospitalization and ICU admission (odds ratio [OR] > 4). Asthma, obesity, chronic kidney disease, sickle cell disease, bone marrow transplantation, and neurologic disorders were associated with hospitalization (adjusted odds ratio [AOR] > 2). Malignancy, intellectual disability, and prematurity were associated with ICU admission (AOR > 4). Comorbidities are significantly associated with hospitalization/ICU admission among children with COVID-19.

The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study.

PURPOSE: Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS: A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS: A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.

Clinical and genomic signatures of SARS-CoV-2 Delta breakthrough infections in New York.

BACKGROUND: In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. METHODS: We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. FINDINGS: We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. INTERPRETATION: We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. FUNDING: The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

Impact of Prenatal SARS-CoV-2 Infection on Infant Emergency Department Visits and Hospitalization.

To better understand the impact of prenatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on infants, this study sought to compare the risk of hospital visits and of postnatal SARS-CoV-2 infection between infants born to mothers with and without prenatal SARS-CoV-2 infection. In this retrospective observational cohort study of 6871 mothers and their infants, overall rates of emergency department (ED) visits and hospital admissions in the first 90 days of life were similar for infants born to mothers with and without prenatal SARS-CoV-2 infection. Infants born to negative mothers were more likely than infants of positive mothers to be hospitalized after ED visit (relative risk: 3.76; 95% confidence interval: 1.27-11.13, P = .003). Five infants tested positive; all were born to negative mothers, suggesting that maternal prenatal SARS-CoV-2 infection may protect infants from postnatal infection. The lower acuity ED visits for infants born to mothers with prenatal SARS-CoV-2 infection may reflect a heightened level of concern among these mothers.

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City.

The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.

COVID-19 vaccination in pregnancy: early experience from a single institution.

OBJECTIVE: Pregnant women are at increased risk for morbidity owing to infection with the COVID-19 virus.1 Vaccination presents an important strategy to mitigate illness in this population. However, there is a paucity of data on vaccination safety and pregnancy outcomes because pregnant women were excluded from the initial phase III clinical trials. Our objective was to describe the maternal, neonatal, and obstetrical outcomes of women who received a messenger RNA (mRNA) COVID-19 vaccination while pregnant during the first 4 months of vaccine availability. STUDY DESIGN: This was an institutional review board-approved descriptive study of pregnant women at New York University Langone Health who received at least 1 dose of an mRNA COVID-19 vaccination approved by the US Food and Drug Administration (FDA) (Pfizer-BioNTech or Moderna) from the time of the FDA Emergency Use Authorization to April 22, 2021. Eligible women were identified via search of the electronic medical record (EMR) system. Vaccine administration was ascertained via immunization records from the New York State Department of Health. Women were excluded if they were vaccinated before conception or during the postpartum period. Charts were reviewed for maternal demographics and pregnancy outcomes. Descriptive analyses were performed using the R software version 4.0.2 (The R Foundation, Boston, MA). RESULTS: We identified 424 pregnant women who received an mRNA vaccination. Of those, 348 (82.1%) received both doses and 76 (17.9%) received only 1 dose. The maternal characteristics and vaccination information are shown in Table 1. Of the included women, 4.9% had a history of a confirmed COVID-19 diagnosis before vaccination. After vaccination, no patient in our cohort was diagnosed with COVID-19. In terms of the pregnancy outcomes, 9 women had spontaneous abortions, 3 terminated their pregnancies, and 327 have ongoing pregnancies. Of the women included, 85 delivered liveborn infants. There were no stillbirths in our population. Of the 9 spontaneous abortions, 8 occurred during the first trimester at a range of 6 to 13 weeks' gestation. There was 1 second trimester loss. The rate of spontaneous abortion among women vaccinated in the first trimester was 6.5%. The 327 women with ongoing pregnancies have been followed for a median of 4.6 weeks (range, 0-17 weeks) following their most recent dose. A total of 113 (34.6%) women, initiated vaccination during the first trimester, 178 (54.4%) initiated vaccination during the second trimester, and 36 (11.0%) during the third trimester. Following the vaccination, 2 fetuses (0.6%) developed intrauterine growth restriction, whereas 5 (1.5%) were diagnosed with anomalies. Outcomes for the 85 women who delivered are shown in Table 2. Of the women who delivered, 18.8% were diagnosed with a hypertensive disorder of pregnancy. The rate of preterm birth was 5.9%. One preterm delivery was medically indicated, whereas the remaining 3 were spontaneous. A total of 15.3% of neonates required admission to the neonatal intensive care unit (NICU). Of the NICU admissions, 61.5% were because of hypoglycemia or an evaluation for sepsis. Other reasons for admission included prematurity, hypothermia, and transient tachypnea of the newborn. Of all the neonates, 12.2% were small for gestational age (SGA) per the World Health Organization standards. CONCLUSION: This series describes our experience with women who received an mRNA COVID-19 vaccine during pregnancy. In line with other published findings,2 we observed no concerning trends. There were no stillbirths. Our 6.5% rate of spontaneous abortion is within the expected rate of 10%,3 and our preterm birth rate of 5.9% is below the national average of 9.5%.4 Our rate of pregnancy-related hypertensive disorders is higher than our baseline institutional rate of 9.5%, however, this may be because of the underlying characteristics of our study population or skewing of our small sample size. Our 12.2% rate of SGA neonates is near the expected value based on the definition that 10% of neonates will be SGA at birth. The NICU admission rate is at par with our institutional rate of 12%. To date, most women in this series have had uncomplicated pregnancies and have delivered at-term. Strengths of this study include using the EMR system to identify subjects and gather data. We did not rely on self-enrollment and self-report, thereby reducing selection and recall bias. By performing manual chart reviews, we obtained detailed and reliable information about individual patients. One limitation of this study is the lack of a matched control group consisting of unvaccinated pregnant women and therefore direct conclusions could not be drawn about the relative risks of complications. In addition, our cohort is small and may not be generalizable. Finally, many women included are healthcare workers who had early access to vaccinations. As more pregnant women become eligible for the COVID-19 vaccinations, there is an urgent need to report on the maternal, neonatal, and obstetrical outcomes of COVID-19 vaccinations during pregnancy. The results of this study can be used to counsel and reassure pregnant patients facing this decision.

SARS-CoV-2 Among Infants <90 Days of Age Admitted for Serious Bacterial Infection Evaluation.

OBJECTIVES: To determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants hospitalized for a serious bacterial infection (SBI) evaluation and clinically characterize young infants with SARS-CoV-2 infection. METHODS: A retrospective chart review was conducted on infants <90 days of age hospitalized for an SBI evaluation. The study was conducted at 4 inpatient facilities in New York City from March 15, 2020, to December 15, 2020. RESULTS: We identified 148 SBI evaluation infants who met inclusion criteria. A total of 22 infants (15%) tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction; 31% of infants admitted during periods of high community SARS-CoV-2 circulation tested positive for SARS-CoV-2, compared with 3% when community SARS-CoV-2 circulation was low (P < .001). The mean age of infants with SARS-CoV-2 was higher than that of SARS-CoV-2-negative infants (33 [SD: 17] days vs 23 [SD: 23] days, respectively; P = .03), although no age difference was observed when analysis was limited only to febrile infants. An isolated fever was the most common presentation of SARS-CoV-2 (n = 13; 59%). Admitted infants with SARS-CoV-2 were less likely to have positive urine culture results (n = 1 [5%] versus n = 25 [20%], respectively; P = .002), positive cerebrospinal culture results (n = 0 [0%] versus n = 5 [4%], respectively; P = .02), or be admitted to intensive care (n = 2 [9%] versus n = 47 [37%]; P < .001), compared with infants without SARS-CoV-2. CONCLUSIONS: SARS-CoV-2 was common among young infants hospitalized for an SBI evaluation during periods of high but not low community SARS-CoV-2 circulation in New York City, although most infants did not require intensive care admission.

Development and validation of a machine learning model to predict mortality risk in patients with COVID-19.

New York City quickly became an epicentre of the COVID-19 pandemic. An ability to triage patients was needed due to a sudden and massive increase in patients during the COVID-19 pandemic as healthcare providers incurred an exponential increase in workload,which created a strain on the staff and limited resources. Further, methods to better understand and characterise the predictors of morbidity and mortality was needed. METHODS: We developed a prediction model to predict patients at risk for mortality using only laboratory, vital and demographic information readily available in the electronic health record on more than 3395 hospital admissions with COVID-19. Multiple methods were applied, and final model was selected based on performance. A variable importance algorithm was used for interpretability, and understanding of performance and predictors was applied to the best model. We built a model with an area under the receiver operating characteristic curve of 83-97 to identify predictors and patients with high risk of mortality due to COVID-19. Oximetry, respirations, blood urea nitrogen, lymphocyte per cent, calcium, troponin and neutrophil percentage were important features, and key ranges were identified that contributed to a 50% increase in patients' mortality prediction score. With an increasing negative predictive value starting 0.90 after the second day of admission suggests we might be able to more confidently identify likely survivors DISCUSSION: This study serves as a use case of a machine learning methods with visualisations to aide clinicians with a better understanding of the model and predictors of mortality. CONCLUSION: As we continue to understand COVID-19, computer assisted algorithms might be able to improve the care of patients.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Febrile Infants Without Respiratory Distress.

We report 2 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time reverse-transcription polymerase chain reaction-based testing for SARS-CoV-2 for febrile infants in an outbreak setting.

Cerebrospinal fluid in COVID-19: A systematic review of the literature.

OBJECTIVE: We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. METHODS: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. RESULTS: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. CONCLUSION: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS- CoV-2 are unlikely to be related to direct viral neuroinvasion.

Characteristics of Hospitalized Children With SARS-CoV-2 in the New York City Metropolitan Area.

OBJECTIVES: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0-21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support. RESULTS: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care (P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002). CONCLUSIONS: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care.

Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.

Impact of Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Detection on Breastfeeding Due to Infant Separation at Birth.

OBJECTIVE: To assess the impact of separation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive mother-newborn dyads on breastfeeding outcomes. STUDY DESIGN: This observational longitudinal cohort study of mothers with SARS-CoV-2 PCR-and their infants at 3 NYU Langone Health hospitals was conducted between March 25, 2020, and May 30, 2020. Mothers were surveyed by telephone regarding predelivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to coronavirus disease-2019 (COVID-19). RESULTS: Of the 160 mother-newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. There was no significant difference in the predelivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads both in the hospital (P < .001) and at home (P = .012). Only 2 mothers in each group reported expressed breast milk as the hospital feeding source (5.6% of unseparated vs 4.1% of separated). COVID-19 was more commonly cited as the reason for change in the separated group (49.0% vs 16.7%; P < .001). When the dyads were further stratified by symptom status into 4 groups-asymptomatic separated, asymptomatic unseparated, symptomatic separated, and symptomatic unseparated-the results remained unchanged. CONCLUSIONS: In the setting of COVID-19, separation of mother-newborn dyads impacts breastfeeding outcomes, with lower rates of breastfeeding both during hospitalization and at home following discharge compared with unseparated mothers and infants. No evidence of vertical transmission was observed; 1 case of postnatal transmission occurred from an unmasked symptomatic mother who held her infant at birth.

Outcomes of Maternal-Newborn Dyads After Maternal SARS-CoV-2.

BACKGROUND AND OBJECTIVES: Infection with a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. There are limited data describing the impact of SARS-CoV-2 infection on pregnant mothers and their newborns. The objective of this study is to describe characteristics and outcomes of maternal-newborn dyads with confirmed maternal SARS-CoV-2. METHODS: This was a multicenter, observational, descriptive cohort study with data collection from charts of maternal-newborn dyads who delivered at 4 major New York City metropolitan area hospitals between March 1 and May 10, 2020, with maternal SARS-CoV-2 infection. RESULTS: There were a total of 149 mothers with SARS-CoV-2 infection and 149 newborns analyzed (3 sets of twins; 3 stillbirths). Forty percent of these mothers were asymptomatic. Approximately 15% of symptomatic mothers required some form of respiratory support, and 8% required intubation. Eighteen newborns (12%) were admitted to the ICU. Fifteen (10%) were born preterm, and 5 (3%) required mechanical ventilation. Symptomatic mothers had more premature deliveries (16% vs 3%, P = .02), and their newborns were more likely to require intensive care (19% vs 2%, P = .001) than asymptomatic mothers. One newborn tested positive for SARS-CoV-2, which was considered a case of horizontal postnatal transmission. CONCLUSIONS: Although there was no distinct evidence of vertical transmission from mothers with SARS-CoV-2 to their newborns, we did observe perinatal morbidities among both mothers and newborns. Symptomatic mothers were more likely to experience premature delivery and their newborns to require intensive care.

Importance of Pediatric Inclusion in COVID-19 Therapeutic Trials.

Pediatric patients are excluded from most coronavirus disease 2019 (COVID-19) therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials, which enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.