Video Abstract Video Abstract The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-γ release assays (IGRAs) may be less sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those <5 years old. Children <15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT.TB test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease. Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were <5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%–75%), with wide confidence intervals (CIs). Specificities for TST, QFT-GIT, and T-SPOT were 73.4% (95% CI: 71.9–74.8), 90.1% (95% CI: 89.1–91.1), and 92.9% (95% CI: 92.0–93.7), respectively. Positive and negative predictive values for TST, QFT-GIT, and T-SPOT were 0.2 (95% CI: 0.1–0.8), 0.9 (95% CI: 0.3–2.5), and 0.8 (95% CI: 0.2–2.9) and 99.9 (95% CI: 99.7–100), 100 (95% CI: 99.8–100), and 99.9 (95% CI: 99.8–100), respectively. Of 533 children with TST-positive, IGRA-negative results not treated for LTBI, including 54 children <2 years old, none developed disease. Although both types of tests poorly predict disease progression, IGRAs are no less predictive than the TST and offer high specificity and negative predictive values. Results from this study support the use of IGRAs for children, especially those who are not born in the United States.

Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction–confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population–pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1–10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUC_τ, C_max, and C_τ) were largely overlapping but modestly increased (remdesivir, 33%–129%; GS-704277, 37%–124%; GS-441524, 0%–60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

Monitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection. We estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March-October 2021, during which the Delta variant became predominant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE ≥ 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2. Among individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%-93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%-93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%-97.2%) after Moderna vaccine. VE was estimated to be lower ≥ 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups. VE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection during the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination.

We characterize the overall incidence and risk factors for breakthrough infection among fully vaccinated participants in the North Carolina COVID-19 Community Research Partnership cohort. Among 15,808 eligible participants, 638 reported a positive SARS-CoV-2 test after vaccination. Factors associated with a lower risk of breakthrough in the time-to-event analysis included older age, prior SARS-CovV-2 infection, higher rates of face mask use, and receipt of a booster vaccination. Higher rates of breakthrough were reported by participants vaccinated with BNT162b2 or Ad26.COV2.S compared to mRNA-1273, in suburban or rural counties compared to urban counties, and during circulation of the Delta and Omicron variants.

Longitudinal virological and serological surveillance is essential for understanding severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) transmission among children but requires increased test capacity. We assessed the uptake of serial at-home testing in children (2–17 years) via mailed SARS-CoV-2 antibody and molecular tests. Completion rates demonstrated the feasibility and sustainability of at-home testing across age groups.

During the COVID-19 pandemic, longitudinal serological surveillance was critical to accurately assess the cumulative incidence of COVID-19 and monitor population-level immunity among children. We characterized the epidemiology of COVID-19 among North and South Carolina children using remote electronic symptom surveillance and serial at-home antibody testing in 2–17-year-old children from April to December 2021. We estimated accumulation of infection-induced antibodies, defined as seropositivity before vaccination. Reported novel symptoms were characterized for seropositive and seronegative participants. A total of 1058 children (median age 10 years (IQR 7–13)) participated in symptom surveillance. Estimated cumulative prevalence of infection-induced antibody increased from 0% (0–60%) to 85.7% (31.6–97%), 3.1% (0–9.0%) to 61.7% (46.1–72.7%) and 5.6% (0–15.6%) to 75% (59.9–84.4%), respectively, among those aged 2–4, 5–11 and 12–17 years. Determinants of seropositivity included Black race (OR 2.06 (1.19 to 3.47)) and having >5 household members (OR 3.05 (1.21 to 7.45)). Participants seroconverting reported mostly respiratory or systemic symptoms, but 52% (28/52) were asymptomatic. We demonstrate the role of at-home testing in trending SARS-CoV-2 seroprevalence in a community cohort of children. Such regional serological surveillance complements national data for a more complete assessment of SARS-CoV-2 burden and transmission. Future applications of the remote surveillance platform may be leveraged for characterizing the epidemiology of novel pathogens.