Long-term immune response to SARS-CoV-2 infection and vaccination in children and adolescents.

BACKGROUND: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents. METHODS: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed. RESULTS: N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20). CONCLUSIONS: This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules. IMPACT: This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection. Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti-SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months. This information can inform future SARS-CoV-2 vaccination schedules in this age group.

A National, Electronic Health Record-Based Study of Perinatal Hemorrhagic and Ischemic Stroke.

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke. METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. Odds ratios were calculated against a control group. RESULTS: A total of 535 (63%) neonates were identified with ischemic stroke and 312 (37%) with hemorrhagic stroke. The most common exposures for ischemic stroke were sepsis (n = 82, 15.33%), hypoxic injury (n = 61, 11.4%), and prematurity (n = 49, 9.16%). The most common comorbidities for hemorrhagic stroke were prematurity (n = 81, 26%) and sepsis (n = 63, 20%). No perinatal ischemic stroke patients had diagnosis codes for cytomegalovirus disease. Procedure and diagnosis codes related to critical illness, including intubation and resuscitation, were prominent in both hemorrhagic (n = 46, 15%) and ischemic stroke (n = 45, 8%). CONCLUSION: This electronic health record-based study of perinatal stroke, the largest of its kind, demonstrated a wide variety of comorbid conditions with ischemic and hemorrhagic stroke. Sepsis, prematurity, and hypoxic injury are associated with perinatal hemorrhagic and ischemic stroke, though prevalence varies between types. Much of our data were similar to prior studies, which lends validity to the electronic health record database in studying perinatal stroke.

SARS-CoV-2 Serostatus and COVID-19 Illness Characteristics by Variant Time Period in Non-Hospitalized Children and Adolescents.

OBJECTIVE: To describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample. DESIGN: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old. SETTING: State of Texas, USA. PARTICIPANTS: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOME(S) AND MEASURE(S): SARS-CoV-2 antibody status was assessed by the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Self-reported antigen or PCR COVID-19 test results and symptom status were also collected. RESULTS: Over half (57.2%) of the sample (N = 3911) was antibody positive. Symptomatic infection increased over time from 47.09% during the pre-Delta variant time period, to 76.95% during Delta, to 84.73% during Omicron, and to 94.79% during the Omicron BA.2. Those who were not vaccinated were more likely (OR 1.71, 95% CI 1.47, 2.00) to be infected versus those fully vaccinated. CONCLUSIONS: Results show an increase in symptomatic COVID-19 infection among non-hospitalized children with each progressive variant over the past two years. Findings here support the public health guidance that eligible children should remain up to date with COVID-19 vaccinations.

Incidence and Predictors of Breakthrough and Severe Breakthrough Infections of SARS-CoV-2 After Primary Series Vaccination in Adults: A Population-Based Survey of 22 575 Participants.

BACKGROUND: Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization). METHODS: In total, 89 762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively. RESULTS: The incidence was 0.45 (95% confidence interval [CI], .38-.50) during pre-Delta, 2.80 (95% CI, 2.25-3.14) during Delta, and 11.2 (95% CI, 8.80-12.95) during Omicron, per 10 000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073-1.441), larger household size (OR = 1.251 [95% CI, 1.048-1.494] for 3-5 vs 1 and OR = 1.726 [95% CI, 1.317-2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122-1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs. CONCLUSIONS: Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.

Antibody Duration After Infection From SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey.

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).

Methodology to estimate natural- and vaccine-induced antibodies to SARS-CoV-2 in a large geographic region.

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning September 30, 2020. Along with state vaccination data, as of October 31, 2021, the estimated percentage of those 5 years or older with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.0% (95% CI = (33.1%, 36.9%)). This is 3× higher than, state-confirmed COVID-19 cases (11.83%) for all ages. The percentage with naturally occurring or vaccine-induced antibodies (total seroprevalence) is 77.42%. This methodology is integral to pandemic preparedness as accurate estimates of seroprevalence can inform policy-making decisions relevant to SARS-CoV-2.

Comparison of Persistent Symptoms Following SARS-CoV-2 Infection by Antibody Status in Nonhospitalized Children and Adolescents.

BACKGROUND: The prevalence of long-term symptoms of coronavirus disease 2019 (COVID-19) in nonhospitalized pediatric populations in the United States is not well described. The objective of this analysis was to examine the presence of persistent COVID symptoms in children by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status. METHODS: Data were collected between October 2020 and May 2022 from the Texas Coronavirus Antibody REsponse Survey, a statewide prospective population-based survey among 5-90 years old. Serostatus was assessed by the Roche Elecsys Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein. Self-reported antigen/polymerase chain reaction COVID-19 test results and persistent COVID symptom status/type/duration were collected simultaneously. Risk ratios for persistent COVID symptoms were calculated versus adults and by age group, antibody status, symptom presence/severity, variant, body mass index and vaccine status. RESULTS: A total of 82 (4.5% of the total sample [n = 1813], 8.0% pre-Delta, 3.4% Delta and beyond) participants reported persistent COVID symptoms (n = 27 [1.5%] 4-12 weeks, n = 58 [3.3%] >12 weeks). Compared with adults, all pediatric age groups had a lower risk for persistent COVID symptoms regardless of length of symptoms reported. Additional increased risk for persistent COVID symptoms >12 weeks included severe symptoms with initial infection, not being vaccinated and having unhealthy weight (body mass index ≥85th percentile for age and sex). CONCLUSIONS: These findings highlight the existence of nonhospitalized youth who may also experience persistent COVID symptoms. Children and adolescents are less likely to experience persistent COVID symptoms than adults and more likely to be symptomatic, experience severe symptoms and have unhealthy weight compared with children/adolescents without persistent COVID symptoms.

Machine learning prediction of the adverse outcome for nontraumatic subarachnoid hemorrhage patients.

OBJECTIVE: Subarachnoid hemorrhage (SAH) is often devastating with increased early mortality, particularly in those with presumed delayed cerebral ischemia (DCI). The ability to accurately predict survival for SAH patients during the hospital course would provide valuable information for healthcare providers, patients, and families. This study aims to utilize electronic health record (EHR) data and machine learning approaches to predict the adverse outcome for nontraumatic SAH adult patients. METHODS: The cohort included nontraumatic SAH patients treated with vasopressors for presumed DCI from a large EHR database, the Cerner Health Facts® EMR database (2000-2014). The outcome of interest was the adverse outcome, defined as death in hospital or discharged to hospice. Machine learning-based models were developed and primarily assessed by area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2467 nontraumatic SAH patients (64% female; median age [interquartile range]: 56 [47-66]) who were treated with vasopressors for presumed DCI were included in the study. 934 (38%) patients died or were discharged to hospice. The model achieved an AUC of 0.88 (95% CI, 0.84-0.92) with only the initial 24 h EHR data, and 0.94 (95% CI, 0.92-0.96) after the next 24 h. INTERPRETATION: EHR data and machine learning models can accurately predict the risk of the adverse outcome for critically ill nontraumatic SAH patients. It is possible to use EHR data and machine learning techniques to help with clinical decision-making.

Vasopressor treatment and mortality following nontraumatic subarachnoid hemorrhage: a nationwide electronic health record analysis.

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH. METHODS: The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH (based on ICD-9 codes) who were treated with the vasopressors dopamine, phenylephrine, or norepinephrine. The relationship between the initial choice of vasopressor therapy and the primary outcome, which was defined as in-hospital death or discharge to hospice care, was examined. RESULTS: In total, 2634 patients were identified with nontraumatic SAH who were treated with a vasopressor. In this cohort, the average age was 56.5 years, 63.9% were female, and 36.5% of patients developed the primary outcome. The incidence of the primary outcome was higher in those initially treated with either norepinephrine (47.6%) or dopamine (50.6%) than with phenylephrine (24.5%). After adjusting for possible confounders using propensity score methods, the adjusted OR of the primary outcome was higher with dopamine (OR 2.19, 95% CI 1.70-2.81) and norepinephrine (OR 2.24, 95% CI 1.80-2.80) compared with phenylephrine. Sensitivity analyses using different variable selection procedures, causal inference models, and machine-learning methods confirmed the main findings. CONCLUSIONS: In patients with nontraumatic SAH, phenylephrine was significantly associated with reduced mortality in SAH patients compared to dopamine or norepinephrine. Prospective randomized clinical studies are warranted to confirm this finding.

Pulmonary Complications due to Esophagectomy.

INTRODUCTION: Esophageal carcinoma is the scourge of human beings. Pulmonary complications in patients who have undergone operation are common (20-30% of cases) and there are no suitable tools and ways to predict these complications. METHODS: During a period of 10 years, from March 1998 to February 2007, 200 patients (150 male and 50 female) underwent Esophagectomy due to esophageal carcinoma in thoracic surgery ward retrospectively. Complications include the length of hospitalization, mechanical ventilation, morbidity and mortality. Patients' risk factors include age, preoperative chemo-radiotherapy, stage of the disease and preoperative spirometry condition. RESULTS: WE GROUPED OUR PATIENTS INTO THREE CATEGORIES: Normal (FEV1 ≥ 80% predicted), mildly impaired (FEV1 65% to 79% predicted), more severely impaired (FEV1 < 65% predicted).Although almost all patients had radiographic pulmonary abnormalities, significant pulmonary complications occurred in 40 patients (20%) which underwent Esophagectomy. Pleural effusion and atelectasia in 160 patients (80%). 24 patients needed chest-tube insertion. 20 patients (10%) developed ARDS. 14 patients (7%) developed chylothorax. 20 patients (10%) of patients died during their postoperative hospital stay. 30 patients (15%) required mechanical ventilation for greater than 48 hours. CONCLUSION: We reviewed a number of preoperative clinical variables to determine whether they contributed to postoperative pulmonary complications as well as other outcomes. In general, age, impaired pulmonary function especially in those patients with FEV1 less than 65% predicted was associated with prolonged hospital length of stay (LOS). In fact pulmonary complications rate after Esophagectomy are high and there was associated mortality and morbidity.

Nomograms of Iranian fetal middle cerebral artery Doppler waveforms and uniformity of their pattern with other populations' nomograms.

BACKGROUND: Doppler flow velocity waveform analysis of fetal vessels is one of the main methods for evaluating fetus health before labor. Doppler waves of middle cerebral artery (MCA) can predict most of the at risk fetuses in high risk pregnancies. In this study, we tried to obtain normal values and their nomograms during pregnancy for Doppler flow velocity indices of MCA in 20-40 weeks of normal pregnancies in Iranian population and compare their pattern with other countries' nomograms. METHODS: During present descriptive cross-sectional study, 1037 normal pregnant women with 20th-40th week gestational age were underwent MCA Doppler study. All cases were studied by gray scale ultrasonography initially and Doppler of MCA afterward. Resistive Index (RI), Pulsative Index (PI), Systolic/Diastolic ratio (S/D ratio), and Peak Systolic Velocity (PSV) values of MCA were determined for all of the subjects. RESULTS: Results of present study showed that RI, PI, S/D ratio values of MCA decreased with parabolic pattern and PSV value increased with simple pattern, as gestational age progressed. These changes were statistically significant (P=0.000 for all of indices) and more characteristic during late weeks of pregnancy. CONCLUSION: Values of RI, PI and S/D ratio indices reduced toward the end of pregnancy, but PSV increased. Despite the trivial difference, nomograms of various Doppler indices in present study have similar pattern with other studies.