Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Comparisons of Pediatric and Adult SARS-CoV-2-Specific Antibodies up to 6 Months after Infection, Vaccination, or Hybrid Immunity.

BACKGROUND: Characterization of longitudinal SARS-CoV-2-specific antibody responses in children following infection and vaccination is needed to inform SARS-CoV-2 vaccine policy decisions for children, which may differ from adults. METHODS: We enrolled individuals at the time of SARS-CoV-2 infection or vaccination for longitudinal serological testing and compared SARS-CoV-2-spike-specific IgG and neutralization activity in children and adults stratified by infection and vaccination status using enzyme-linked immunosorbent and virus neutralization assays. RESULTS: Between June 2020 and December 2022, we collected sera from 669 participants aged 40 days to 55 years, including 330 unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection, 180 vaccinated SARS-CoV-2-naïve individuals, and 159 vaccinated previously infected individuals. Half (n = 330, 49.3%) were children. SARS-CoV-2-specific IgG and neutralization activity in children < 12 years old in response to infection persisted at higher levels than those of adults through at least 6 months (spike-specific IgG levels, 2.05 [95% CI: 1.4-3.1] times higher than adults; neutralizing activity, median 88.8 vs 75.2%, respectively, p = .04). In addition, all pediatric participants had significantly higher IgG levels compared with adults at 6 months following infection or vaccination, regardless of prior infection status. Vaccine-induced SARS-CoV-2-specific IgG responses in previously infected individuals persisted at higher levels than those from infection alone at 6 months (median AUC, children 5-11 years old, 9115 vs 368; adolescents 3613 vs 475; adults 1956 vs 263, all p < .001). CONCLUSIONS: These data demonstrate the robust and persistent immunologic response of SARS-CoV-2 vaccination in children and emphasize the benefit of vaccination after SARS-CoV-2 infection.

Characteristics and Clinical Outcomes of Vaccine-Eligible US Children Under-5 Years Hospitalized for Acute COVID-19 in a National Network.

BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. RESULTS: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. CONCLUSIONS: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.

Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19-Associated Hospitalizations in Infants Aged <6 Months During SARS-CoV-2 Omicron Predominance - 20 States, March 9, 2022-May 31, 2023.

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Effect of wash media type during PBMC isolation on downstream characterization of SARS-CoV-2-specific T cells.

Protocols for the isolation of peripheral blood mononuclear cells (PBMCs) from whole blood vary greatly between laboratories, especially in published studies of SARS-CoV-2-specific T cell responses following infection and vaccination. Research on the effects of different wash media types or centrifugation speeds and brake usage during the PBMC isolation process on downstream T cell activation and functionality is limited. Blood samples from 26 COVID-19-vaccinated participants were processed with different PBMC isolation methods using either PBS or RPMI as the wash media with high centrifugation speed and brakes or RPMI as the wash media with low speed and brakes (RPMI+ method). SARS-CoV-2 spike-specific T cells were quantified and characterized via a flow cytometry-based activation induced markers (AIM) assay and an interferon-γ (IFNγ) FluoroSpot assay and responses were compared between processing methods. Samples washed with RPMI showed higher AIM+ CD4 T cell responses than those washed with PBS and showed a shift away from naïve and towards an effector memory phenotype. The activation marker OX40 showed higher SARS-CoV-2 spike-induced upregulation on RPMI-washed CD4 T cells, while differences in CD137 upregulation were minimal between processing methods. The magnitude of the AIM+ CD8 T cell response was similar between processing methods but showed higher stimulation indices. Background frequencies of CD69+ CD8 T cells were increased in PBS-washed samples and were associated with higher baseline numbers of IFNγ-producing cells in the FluoroSpot assay. Slower braking in the RPMI+ method did not improve detection of SARS-CoV-2-specific T cells and caused longer processing times. Thus, the use of RPMI media with full centrifugation brakes during the wash steps of PBMC isolation was found to be most effective and efficient. Further studies are needed to elucidate the pathways involved in RPMI-mediated preservation of downstream T cell activity.

Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations.

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-control Investigation.

BACKGROUND: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. METHODS: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. RESULTS: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. CONCLUSIONS: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C.

Factors Associated With COVID-19 Non-vaccination in Adolescents Hospitalized Without COVID-19.

BACKGROUND: Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥ 16 years in December 2020 and for adolescents 12-15 years in May 2021. Despite the clear benefits and favorable safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12-18 years of age. METHODS: Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12-18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interviews and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of the COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination. RESULTS: Among 1665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p < .01) and resided in areas with higher social vulnerability index (SVI) scores (median 0.6 vs 0.5, p < .001) than vaccinated adolescents. Residence in the Midwest [aOR 2.60 (95% CI: 1.80, 3.79)] or South [aOR 2.49 (95% CI: 1.77, 3.54)] US census regions, rarely or never receiving influenza vaccine [aOR 5.31 (95% CI: 3.81, 7.47)], and rarely or never taking precautions against COVID-19 [aOR 3.17 (95% CI: 1.94, 5.31)] were associated with non-vaccination against COVID-19. CONCLUSIONS: Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination.

BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. METHODS: In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. RESULTS: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. CONCLUSIONS: Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.

Parental attitudes in the pediatric emergency department about the COVID-19 vaccine.

BACKGROUND: COVID-19 vaccinations are now recommended in the United States (U.S.) for children ≥ 6 months old. However, pediatric vaccination rates remain low, particularly in the Hispanic/Latinx population. OBJECTIVE: Using the 4C vaccine hesitancy framework (calculation, complacency, confidence, convenience), we examined parental attitudes in the emergency department (ED) towards COVID-19 vaccination, identified dimensions of parental vaccine hesitancy, and assessed parental willingness to have their child receive the COVID-19 vaccine. METHODS: As part of a larger multi-methods study examining influenza vaccine hesitancy, we conducted interviews that included questions about COVID-19 vaccine authorization for children. We used directed content analysis to extract qualitative themes from 3 groups of parents in the ED: Hispanic/Latinx Spanish speaking (HS), Hispanic/Latinx English speaking (HE), non-Hispanic/non-Latinx White English speaking (WE). Themes were triangulated with the Parent Attitudes about Childhood Vaccines (PACV) survey, where higher scores indicate increased vaccine hesitancy. RESULTS: Factors influencing vaccine hesitancy were mapped to the 4C framework from 58 sets of interviews and PACVs. HE and HS parents, compared to WE parents, had less knowledge about COVID-19 and its vaccine, and more beliefs in COVID-19 vaccine myths. However, both HS and HE parent groups were more inclined to endorse COVID-19 vaccine effectiveness as a reason to have their children vaccinated. HS parents felt that COVID-19 increased their fear of illnesses in general and were worried about confusing COVID-19 with other infections. Median PACV scores of HS (Mdn = 20) and HE (Mdn = 20) parent groups were higher than of WE parents (Mdn = 10), but parental willingness to have their child receive COVID-19 vaccination was similar across groups. CONCLUSIONS: Higher COVID-19 vaccine hesitancy among HS and HE parents compared to WE parents may be attributed to insufficient knowledge about COVID-19, its vaccine, along with COVID-19 vaccine myths. Efforts to provide targeted vaccine education to different populations is warranted.

COVID-19 outcomes in children, adolescents and young adults with cancer.

Pediatric oncology patients are at risk for poor outcomes with respiratory viral infections. Outcome data for COVID-19 in children and young adults with cancer are needed; data are sparse for obese/overweight and adolescent and young adult subgroups. We conducted a single center cohort study of COVID-19 outcomes in patients younger than 25 years with cancer. Candidate hospitalization risk factors were analyzed via univariable and multivariable analyses. Eighty-seven patients with cancer and COVID-19 were identified. Most were Hispanic/Latinx (n = 63, 72%). Forty-two (48%) were overweight/obese. Anticancer therapy included chemotherapy only (n = 64, 74%), chimeric antigen receptor T-cells (CAR-T, n = 7), hematopoietic stem cell transplantation (HSCT, n = 12), or CAR-T and HSCT (n = 4). There was no COVID-19 related mortality. Twenty-six patients (30%) required COVID-19 related hospitalization; 4 required multiple hospitalizations. Nine (10%) had severe/critical infection; 6 needed intensive care. COVID-19 resulted in anticancer therapy delays in 22 (34%) of 64 patients on active therapy (median delay = 14 days). Factors associated with hospitalization included steroids within 2 weeks prior to infection, lymphopenia, previous significant non-COVID infection, and low COVID-19 PCR cycle threshold value. CAR-T recipients with B-cell aplasia tended to have severe/critical infection (3 of 7 patients). A COVID-19 antibody response was detected in 14 of 32 patients (44%). A substantial proportion of COVID-19 infected children and young adults with cancer require inpatient management; morbidity may be high in B-cell immunodeficiency. However, a majority of patients can be taken through chemotherapy without prolonged therapy delays. Viral load is a potential outcome predictor in COVID-19 in pediatric cancer.

Coronavirus Disease 2019 Vaccine Booster Effects Are Seen in Human Milk Antibody Response.

Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM antibodies targeting the SARS CoV-2 receptor binding domain within the spike protein and human milk neutralization activity against SARS CoV-2 in 10 lactating mothers from pre-COVID-19 primary series vaccine to post-booster dose. Human milk SARS CoV-2 specific IgG increased significantly from pre- to post-booster levels (median OD 0.33 vs. 2.02, P = 0.002). The IgG levels post-booster were even higher than the peak level after the primary series (2.02 vs. 0.95, P = 0.03). The increase in SARS CoV-2 specific IgA levels was not significant (0.10 vs. 0.33, P = 0.23). There was a strong correlation between paired maternal blood and milk IgG and IgA levels (IgG rho 0.52, P < 0.001, IgA rho 0.31, P = 0.05). Post-booster neutralizing activity was elevated compared to pre-booster levels (66% vs. 12% inhibition, P = 0.002). COVID-19 vaccine booster elicits SARS CoV-2 specific antibodies in human milk at higher levels compared to the initial primary series. This finding suggests that three doses of COVID-19 mRNA vaccination leads to improved mucosal response in human milk and reinforces current guidance recommending all pregnant or lactating mothers receive full COVID-19 vaccine courses with a booster dose.

Molecular alterations in human milk in simulated maternal nasal mucosal infection with live attenuated influenza vaccination.

Breastfeeding protects against mucosal infections in infants. The underlying mechanisms through which immunity develops in human milk following maternal infection with mucosal pathogens are not well understood. We simulated nasal mucosal influenza infection through live attenuated influenza vaccination (LAIV) and compared immune responses in milk to inactivated influenza vaccination (IIV). Transcriptomic analysis was performed on RNA extracted from human milk cells to evaluate differentially expressed genes and pathways on days 1 and 7 post-vaccination. Both LAIV and IIV vaccines induced influenza-specific IgA that persisted for at least 6 months. Regulation of type I interferon production, toll-like receptor, and pattern recognition receptor signaling pathways were highly upregulated in milk on day 1 following LAIV but not IIV at any time point. Upregulation of innate immunity in human milk may provide timely protection against mucosal infections until antigen-specific immunity develops in the human milk-fed infant.

SARS-CoV-2-specific T cell memory with common TCRαß motifs is established in unvaccinated children who seroconvert after infection.

As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαß repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαß motifs in unvaccinated seroconverted children after their first virus encounter.

Decrease in Pediatric Invasive Pneumococcal Disease During the COVID-19 Pandemic.

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children's hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants.

BACKGROUND: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).

Twelve-Month Longitudinal Serology in SARS-CoV-2 Naïve and Experienced Vaccine Recipients and Unvaccinated COVID-19-Infected Individuals.

Longitudinal data comparing SARS-CoV-2 serology in individuals following infection and vaccination over 12 months are limited. This study compared the magnitude, decay, and variability in serum IgG, IgA, and neutralizing activity induced by natural infection (n = 218) or mRNA vaccination in SARS-CoV-2 naïve (n = 143) or experienced (n = 122) individuals over time using enzyme-linked immunosorbent assays and an in vitro virus neutralization assay. Serological responses were found to be highly variable after natural infection compared with vaccination but durable through 12 months. Antibody levels in vaccinated, SARS-CoV-2 naïve individuals peaked by 1 month then declined through 9 months, culminating in non-detectable SARS-CoV-2-specific serum IgA. Individuals with both infection and vaccination showed SARS-CoV-2-specific IgG and IgA levels that were more robust and slower to decline than the other groups; neutralizing activity remained highest in this group at 9 months past vaccination. These data reinforce the benefit of vaccination after SARS-CoV-2 recovery.