Rawan Korman, Dunia Hatabah, Lou Ann Brown, Frank Harris, Hagar Wilkinson, Chris A Rees, Nitya Bakshi, David R. Archer, Carlton D Dampier, Claudia R. Morri Rawan Korman, Dunia Hatabah, Lou Ann Brown, Frank Harris, Hagar Wilkinson, Chris A Rees, Nitya Bakshi, David R. Archer, Carlton D Dampier, Claudia R. Morri

Background/Objective: Cobalamin (B₁₂) deficiency is reported in 18% of adults with sickle cell disease (SCD) and only 10% without SCD; limited data are available on children. Diagnosing B₁₂ deficiency is challenging given the lack of an established gold standard method of assessment and the unique renal features of SCD. B₁₂ metabolism can be impacted by the clinical use of nitrous oxide gas (N₂O), which is a standard therapy for SCD pain in some European countries. In response to emerging reports of neurologic sequalae in patients with SCD receiving N₂O, we evaluated the prevalence of B₁₂ deficiency in children with SCD pain. Methods: Secondary analysis of prospective blood and urine samples in children aged 3–21 hospitalized with SCD pain. B₁₂ deficiency was defined as plasma methylmalonic acid (MMA) > 592 nmol/L or urine MMA/creatinine ≥ 2.2 mmol/mol. Results: Ninety-four children (13 ± 4 years, 54% female, 68% hemoglobin-SS, and 72% on hydroxyurea) were assessed. Further, 53% (50/94) had B₁₂ deficiency diagnosed by either urine, plasma, or both; 27% (25/94) were deficient based on urine; 39% (37/94) were deficient by plasma; and 13% (12/94) were deficient by both plasma and urine. Plasma MMA and urine MMA/creatinine did not correlate with hemoglobin or mean corpuscular volume. Conclusions: B₁₂ deficiency was common in children with SCD. The absence of a gold standard for diagnosing B₁₂ deficiency compounded with the reliability issues of testing modalities make it impractical to determine whether this is an over- or under-estimation of the true prevalence. Future studies to better understand the dynamics of B₁₂ metabolism during acute and steady states in SCD are warranted and could elucidate the influence of acute SCD pain on these biomarkers.

Determine SARS-CoV-2 IgG antibody incidence over time in unvaccinated pediatric healthcare workers (pHCWs). A prospective longitudinal cohort of unvaccinated pHCWs measuring the incidence of new infection after initial prevalence was established at 4.1% with seropositive predominance in emergency department (ED)-based pHCWs. Serum samples were collected at follow-up visits to detect new SARS-CoV-2 seropositivity. Univariate analysis was performed to estimate different incidence rates between participant demographics, job, employment location, and community risk factors. Anxiety levels about COVID-19 were collected. SARS-CoV-2 antibody decay postinfection and neutralization antibodies were evaluated. Log-linear Poisson regression models were used to estimate incidence. Of 642 initially enrolled, 390 pHCWs presented for at least one follow-up serology test after baseline analysis. The incidence of SARS-CoV-2 seropositivity was 8.2%. The seropositive cohort, like the negative one, consisted mainly of females in non-ED settings and nonphysician roles. There were no statistically significant differences in incidence across variables. Seropositive participants dropped antibody titers by 50% at 3 months. Neutralization antibodies correlated to SARS-CoV-2 binding antibodies (r = 0.43, P < 0.0001). The incidence of seropositivity was 8.2%. Although seropositivity was higher among ED staff during the early stages of the pandemic, this difference declined over time, likely due to the universal adoption of personal protective equipment.

Background: Vaccines against COVID-19 target the spike protein. There is minimal information on longitudinal COVID-19 immune profiling in recovered versus naïve and vaccinated versus non-vaccinated healthcare workers (HCWs). Methods: This is a prospective longitudinal observational cohort of pediatric HCWs (pHCWs) conducted during 2020–2022 at an academic center, exploring the impact of COVID-19 vaccination on immunoglobulin G (IgG) antibody titers over time and cross-reactivity with other coronaviruses, including SARS-CoV-1, MERS-CoV, and seasonal coronaviruses (HCoV-HKU1 and HCoV-OC43). Results: A total of 642 pHCWs initially enrolled, and 337 participants had repeat IgG titers measured post-vaccine and post-booster. Most participants were female, median age range of 31–40 years. Anti-spike was higher in all vaccinated individuals versus non-vaccinated (p < 0.0001) and naïve versus infected (p < 0.0001). A single dose of vaccine was sufficient to attain maximum titers in recovered participants versus naïve who received both doses of vaccine. Anti-spike titers dropped significantly at 9 months after the primary series, whereas sustained anti-spike titers were observed at 9 months post-booster. Conclusions: All vaccinated pHCWs developed antibodies to spike. COVID-19 infection and/or vaccination yielded antibodies that cross-reacted to SARS-CoV-1, MERS-CoV, HCoV-HKU1, and HCoV-OC43. Anti-spike titers were more durable post-booster compared to the primary series. Longitudinal immune profiling of COVID-19 responses provides vital data to shape public health policies, optimize vaccine strategies, and strengthen pandemic preparedness.