Use of COVID-19 Convalescent Plasma for Treatment of Symptomatic SARS-CoV-2 Infection at a Children's Hospital: A Contribution to a Still Inadequate Body of Evidence.

Data on COVID-19 convalescent plasma (CCP) safety and efficacy in children and young adults are limited. This single-center prospective, open-label trial evaluates CCP safety, neutralizing antibody kinetics, and outcomes in children and young adults with moderate/severe COVID-19 (April 2020-March 2021). A total of 46 subjects received CCP; 43 were included in the safety analysis (SAS); 7.0% < 2 years old, 2.3% 2-<6, 27.9% 6-<12, 39.5% 12-<19, and 23.3% > 19 years old; 28 were included in the antibody kinetic analysis (AbKS); 10.7% < 2 years old, 10.7% 6-<12, 53.8% 12-<19, and 25.0% > 19 years old. No adverse events occurred. The median COVID-19 severity score improved (5.0 pre-CCP to 1.0 by day 7; p < 0.001). A rapid increase in the median percentage of inhibition was observed in AbKS (22.5% (13.0%, 41.5%) pre-infusion to 52% (23.7%, 72%) 24 h post-infusion); a similar increase was observed in nine immune-competent subjects (28% (23%, 35%) to 63% (53%, 72%)). The inhibition percentage increased until day 7 and persisted at 21 and 90 days. CCP is well tolerated in children and young adults, providing rapid and robust increased antibodies. CCP should remain a therapeutic option for this population for whom vaccines are not fully available and given that the safety and efficacy of existing monoclonal antibodies and antiviral agents have not been established.

Rapid antibody testing for SARS-CoV-2 vaccine response in pediatric healthcare workers.

BACKGROUND: The durability of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination remains unknown. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for the humoral response to vaccination. METHODS: Study participants (n = 125) included pediatric healthcare workers (HCWs) who had received two doses of BNT162b2 or mRNA-1273. Participants were tested on study entry (March 12, 2021 to April 9, 2021). The mean number of days post second dose was 22 (range 17-36). Participants were tested for IgM/IgG antibodies to the SARS-CoV-2 spike protein with the RightSign COVID-19 IgG/IgM Rapid Test Cassette. ELISA/competitive inhibition ELISA (CI-ELISA) were subsequently run to assess for the neutralization effect and SARS-CoV-2 anti-nucleocapsid IgM/IgG antibodies. RESULTS: Overall, 98.4% of participants were IgG-positive and 0.8% were IgM-positive on rapid RightSign testing. Of those with IgG-positive results, 100% were anti-spike protein IgG-positive on CI-ELISA; none of those who tested IgG-negative via the rapid test were IgG-positive on CI-ELISA. All HCWs who tested RightSign positive demonstrated neutralizing capability on CI-ELISA. Overall, 1.6% demonstrated anti-nucleocapsid IgM antibodies and 5.6% demonstrated anti-nucleocapsid IgG antibodies. CONCLUSIONS: The strong agreement between the rapid RightSign IgG results and confirmatory CI-ELISA testing suggests that this test may be used to assess for positive, and neutralizing, antibody responses to SARS-CoV-2 mRNA vaccination.

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.

Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs. PROCEDURE: In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram. RESULTS: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9. CONCLUSION: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.