Faculty Bibliography

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

BACKGROUND:Many survivors of hemorrhagic stroke have impaired communication. We aimed to identify preadmission, admission, and post-discharge factors associated with self-reported impaired communication after hemorrhagic stroke. DESIGN/METHODS:Patients with intracerebral or subarachnoid hemorrhage (ICH or SAH) admitted at an urban academic medical center were assessed 3-months post-bleed using the communication Quality of Life in Neurological Disorders (Neuro-QoL) short form inventory. Multivariate analysis was performed to evaluate the relationship between impaired communication (Neuro-QoL scaled score < 100) and preadmission, admission, and post-discharge factors. RESULTS:Of 108 patients (68 ICH and 40 SAH), 59 (54.6%) had impaired communication 3-months post-bleed. On multivariate analysis of the full cohort, when controlling for NIHSS score on admission, impaired communication was associated with: retirement prior to admission (OR: 8.18, 95% CI 1.95-40.5, p = 0.005), hospital length-of-stay (OR: 1.11, 95% CI 1.03-1.22, p = 0.012), and cognitive impairment post-bleed (OR: 32.1, 95% CI 8.93-146, p < 0.001). There were 43 (63.2%) ICH patients with impaired communication 3-months post-bleed. On multivariate analysis, impaired communication was associated with: retirement prior to admission (OR: 9.46, 95% CI 1.76-71.8, p = 0.014), supratentorial location (OR: 8.93, 95% CI 1.22-93.6, p = 0.043), hospital length-of-stay (OR: 1.21, 95% CI 1.01-1.45, p = 0.018), and cognitive impairment post-bleed (OR: 16.3, 95% CI 3.58-102, p < 0.001). CONCLUSIONS:Impaired communication after hemorrhagic stroke is more common in patients who were retired prior to admission and who have post-bleed comorbid cognitive impairment. Increased surveillance is recommended for retired and cognitively impaired patients. Additional investigation into the relationship between communication and both retirement status and cognitive impairment is needed.

OBJECTIVES/OBJECTIVE:Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We aimed to evaluate the association between pre-COVID-19 BMI status and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes in children and young adults. METHODS:We conducted a retrospective cohort study using data from 139320 individuals aged 5 to 20 years with confirmed SARS-CoV-2 infection between March 2020 and September 2023 across 20 U.S. pediatric health systems participating in the RECOVER initiative. Pre-infection BMI was defined using measurements obtained within 18 months before the index date and categorized as healthy weight, overweight, obesity, or severe obesity; when multiple values were available, the most recent measurement was selected. We assessed incident postacute cardiovascular, gastrointestinal, and neuropsychiatric symptoms and conditions occurring 28 to 179 days post-infection. Adjusted relative risks (RRs) were estimated using modified Poisson regression models, comparing elevated BMI categories to the healthy weight. FINDINGS/RESULTS:Among 139320 participants (mean [SD] age, 13.0 [4.3] years; 51.6% female), severe obesity was associated with a higher risk of cardiovascular disorders (adjusted RR 2.56; 95% CI 1.93-3.41), particularly hypertension (adjusted RR 3.68; 95% CI 2.65-5.11). Severe obesity was also linked with increased risks of diarrhea (adjusted RR 1.34; 95% CI 1.10-1.64) and gastroesophageal reflux disease (adjusted RR 1.29; 95% CI 1.06-1.58). Associations between BMI and neuropsychiatric outcomes were heterogeneous, with inverse associations observed for some conditions, including anxiety and major depression. INTERPRETATION/CONCLUSIONS:In this cohort study, pre-COVID-19 BMI status was associated with the risk and pattern of postacute cardiovascular and gastrointestinal outcomes among children and young adults. Association between pre-infection BMI and neuropsychiatric outcomes was more variable and should be interpreted with caution. These findings suggest BMI-stratified post-COVID-19 monitoring strategies may help inform long-term care in youth.

BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period. METHODS:This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching. FINDINGS/RESULTS:We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9-1026·5) in the first infection group and 1883·7 (1565·1-2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68-2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15-3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms. INTERPRETATION/CONCLUSIONS:Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies. FUNDING/BACKGROUND:National Institutes of Health.

OBJECTIVE:To evaluate the risks of incident dyslipidemia and abnormal body mass index (BMI) during the 28-179-day post-acute phase after documented SARS-CoV-2 infection in a large pediatric sample. STUDY DESIGN/METHODS:A retrospective cohort study using the RECOVER pediatric electronic health record (EHR) datasets from 25 US children's hospitals and health institutions, from March 2020 to September 2023. This study included 384,289 COVID-19-positive patients aged 0-21 years for dyslipidemia analyses and 285,559 aged 2-21 years for BMI analyses, each with at least 6 months of follow-up. COVID-19-negative controls included 1,080,413 and 817,315 patients, respectively. SARS-CoV-2 infection was defined by a positive polymerase-chain-reaction (PCR), antigen, or serologic test; a clinical diagnosis of COVID-19; or a documented diagnosis of post-acute sequelae of SARS-CoV-2 (PASC). Incident dyslipidemia and abnormal BMI were identified using age-specific laboratory or anthropometric thresholds. Adjusted relative risks (aRRs) were estimated using propensity-score-stratified modified Poisson regression with multiple sensitivity analyses. RESULTS:During the post-acute phase, the COVID-19-positive cohort had higher rates of new-onset composite dyslipidemia (aRR 1.24; 95% CI 1.18-1.29) and abnormal BMI (aRR 1.15; 95% CI, 1.12-1.18). Results were robust to sensitivity and stratified analyses. CONCLUSION/CONCLUSIONS:Children and adolescents with documented COVID-19 infection were associated with an increased risk of new-onset dyslipidemia and abnormal BMI during the post-acute phase, highlighting the need for metabolic monitoring after infection.

OBJECTIVE/UNASSIGNED:The authors sought to determine the relationships among cognitive impairment, psychiatric outcome, and functional status 3 months after a hemorrhagic stroke. METHODS/UNASSIGNED:Patients with nontraumatic intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) were assessed by telephone 3 months after discharge by using the Quality of Life in Neurological Disorders (Neuro-QoL) cognitive function, anxiety, depression, and sleep disturbance short forms, as well as the modified Rankin Scale (mRS). The relationships between poor cognition (Neuro-QoL T score≤50), functional status, and psychiatric outcome among patients with ICH or SAH and patients with ICH only were evaluated. RESULTS/UNASSIGNED:Of 101 patients (N=62 with ICH and N=39 with SAH), 51% had poor cognition 3 months posthemorrhage, with 61% having mRS scores of 3-5, 43% having anxiety, 28% having depression, and 31% having sleep disturbance. Univariate analysis of the full cohort indicated that poor cognition was significantly associated with anxiety, depression, sleep disturbance, and mRS scores of 3-5 (p<0.05). Multivariate analysis revealed that poor cognition was significantly associated with anxiety (OR=4.38, 95% CI=1.30-14.74, p=0.017) and mRS scores of 3-5 (OR=6.15, 95% CI=1.96-19.32, p=0.002). Univariate analysis of the 62 patients with ICH indicated that poor cognition was significantly associated with anxiety, sleep disturbance, and mRS scores of 3-5 (p<0.05). Multivariate analysis revealed that poor cognition was significantly associated with anxiety (OR=10.98, 95% CI=2.32-51.99, p=0.003). CONCLUSIONS/UNASSIGNED:Poor cognition was associated with anxiety 3 months after hemorrhagic stroke. Additional research is needed to understand whether treatment for anxiety would improve cognition in this population.

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes are examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity is confirmed via PCR, serology, or antigen tests, while negativity requires negative test results and no related diagnoses. Risk differences reveal higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children face increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibit elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluated vaccine effectiveness against reinfection with Omicron BA.1/2, BA.4/5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. pediatric institutions. We emulated target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/2 period, vaccination reduced the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/5 period, protection effectiveness in children was 57%, whereas no statistically significant protection was observed in adolescents. During the XBB or later period, no significant protection was observed in either group. In summary, COVID-19 vaccination provided protection against reinfection during early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declined for later variants.

IMPORTANCE/UNASSIGNED:It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications. OBJECTIVE/UNASSIGNED:To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022). Participants included children and adolescents (aged <21 years) with at least 1 baseline visit (24 months to 7 days before the index date) and at least 1 follow-up visit (28 to 179 days after the index date). EXPOSURES/UNASSIGNED:SARS-CoV-2 infection, determined by positive laboratory test results (polymerase chain reaction, antigen, or serologic) or relevant clinical diagnoses. A comparison group included children with documented negative test results and no history of SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Outcomes included new-onset chronic kidney disease (CKD) stage 2 or higher or CKD stage 3 or higher among those without preexisting CKD; composite kidney events (≥50% decline in estimated glomerular filtration rate [eGFR], eGFR ≤15 mL/min/1.73 m2, dialysis, transplant, or end-stage kidney disease diagnosis), and at least 30%, 40%, or 50% eGFR decline among those with preexisting CKD or acute-phase AKI. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models with propensity score stratification. RESULTS/UNASSIGNED:Among 1 900 146 pediatric patients (487 378 with and 1 412 768 without COVID-19), 969 937 (51.0%) were male, the mean (SD) age was 8.2 (6.2) years, and a range of comorbidities was represented. SARS-CoV-2 infection was associated with higher risk of new-onset CKD stage 2 or higher (HR, 1.17; 95% CI, 1.12-1.22) and CKD stage 3 or higher (HR, 1.35; 95% CI, 1.13-1.62). In those with preexisting CKD, COVID-19 was associated with an increased risk of composite kidney events (HR, 1.15; 95% CI, 1.04-1.27) at 28 to 179 days. Children with acute-phase AKI had elevated HRs (1.29; 95% CI, 1.21-1.38) at 90 to 179 days for composite outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study of children and adolescents, SARS-CoV-2 infection was associated with a higher risk of adverse postacute kidney outcomes, particularly among those with preexisting CKD or AKI, suggesting the need for vigilant long-term monitoring.

IMPORTANCE/OBJECTIVE:Prior studies have demonstrated the effectiveness of COVID-19 vaccines in children and adolescents. However, the benefits of vaccination in these age groups with prior infection remain underexplored. OBJECTIVE:To evaluate the effectiveness of COVID-19 vaccination in preventing reinfection with various Omicron subvariants (BA.1/2, BA.4/5, XBB, and later) among 5- to 17-year-olds with prior SARS-CoV-2 infection. DESIGN/METHODS:A target trial emulation through nested designs with distinct study periods. SETTING/METHODS:The study utilized data from the Research COVID to Enhance Recovery (RECOVER) initiative, a national electronic health record (EHR) database comprising 37 U.S. children's hospitals and health institutions. PARTICIPANTS/METHODS:Individuals aged 5-17 years with a documented history of SARS-CoV-2 infection prior to the study start date during a specific variant-dominant period (Delta, BA.1/2, or BA.4/5) who received a subsequent dose of COVID-19 vaccine during the study periods were compared with those with a documented history of infection who did not receive SARS-CoV-2 vaccine during the study period. Those infected within the Delta-Omicron composite period (December 1, 2021, to December 31, 2021) were excluded. The study period was from January 1, 2022, to August 30, 2023, and focused on adolescents aged 12 to 17 years and children aged 5 to 11 years. EXPOSURES/METHODS:At least received one COVID-19 vaccination during the study period vs. no receipt of any COVID-19 vaccine during the study period. MAIN OUTCOMES AND MEASURES/METHODS:The primary outcome is documented SARS-CoV-2 reinfection during the study period (both asymptomatic and symptomatic cases). The effectiveness of the COVID-19 vaccine was estimated as (1- hazard ratio) *100%, with confounders adjusted by a combination of propensity score matching and exact matching. RESULTS:The study analyzed 87,573 participants during the BA.1/2 period, 229,326 during the BA.4/5 period, and 282,981 during the XBB or later period. Among vaccinated individuals, significant protection was observed during the BA.1/2 period, with effectiveness rates of 62% (95% CI: 38%-77%) for children and 65% (95% CI: 32%-81%) for adolescents. During the BA.4/5 period, vaccine effectiveness was 57% (95% CI: 25%-76%) for children, but not statistically significant for adolescents (36%, 95% CI: -16%-65%). For the XBB period, no significant protection was observed in either group, with effectiveness rates of 22% (95% CI: -36%-56%) in children and 34% (95% CI: -10%-61%) in adolescents. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:COVID-19 vaccination provides significant protection against reinfection for children and adolescents with prior infections during the early and mid-Omicron periods. This study also highlights the importance of addressing low vaccination rates in pediatric populations to enhance protection against emerging variants.