COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn.

2023

5296-5303

08/2023

1873-2518

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

10.1016/j.vaccine.2023.06.032

Vaccine

37451878

Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants.

2023

374-376

01/2023

1533-4406

10.1056/NEJMc2210825

N Engl J Med

36630610

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004).

2022

06/2022

Importance: COVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy.

Objective: To measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn.

Design: Prospective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery.

Setting: Multicenter study conducted at 9 academic sites.

Participants: Pregnant participants who received COVID-19 vaccination during pregnancy and their newborns.

Exposures: Primary or booster COVID-19 mRNA vaccination during pregnancy.

Main Outcomes and Measures: SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.

Results: In this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb).

Conclusions and Relevance: COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron.Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses.

Trial Registration: clinical trials.gov; Registration Number: NCT05031468 ; https://clinicaltrials.gov/ct2/show/NCT05031468.

Key Points: What is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn? Receipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant. COVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.

10.1101/2022.06.13.22276354

medRxiv

35734087

A Multicenter Consortium to Define the Epidemiology and Outcomes of Pediatric Solid Organ Transplant Recipients With Inpatient Respiratory Virus Infection.

2018

2018 Mar 10

2048-7207

<p><strong>Background: </strong>Respiratory virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear.</p>

<p><strong>Methods: </strong>A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant. An RVI diagnosis required respiratory symptoms and detection of a virus (ie, human rhinovirus/enterovirus, human metapneumovirus, influenza virus, parainfluenza virus, coronavirus, and/or respiratory syncytial virus). The incidence of RVI was calculated, and the association of baseline SOT factors with subsequent pulmonary complications and death was assessed.</p>

<p><strong>Results: </strong>Of 1096 pediatric SOT recipients (448 liver, 289 kidney, 251 heart, 66 lung, 42 intestine/multivisceral), 159 (14.5%) developed RVI associated with hospitalization within 12 months after their transplant. RVI occurred at the highest rates in intestine/abdominal multivisceral (38%), thoracic (heart/lung) (18.6%), and liver (15.6%) transplant recipients and a lower rate in kidney (5.5%) transplant recipients. RVI was associated with younger median age at transplant (1.72 vs 7.89 years; P &lt; .001) and among liver or kidney transplant recipients with the receipt of a deceased-donor graft compared to a living donor (P = .01). The all-cause and attributable case-fatality rates within 3 months of RVI onset were 4% and 0%, respectively. Multivariable logistic regression models revealed that age was independently associated with increased risk for a pulmonary complication (odds ratio, 1.24 [95% confidence interval, 1.02-1.51]) and that receipt of an intestine/multivisceral transplant was associated with increased risk of all-cause death (odds ratio, 24.54 [95% confidence interval, 1.69-327.96]).</p>

<p><strong>Conclusions: </strong>In this study, hospital-associated RVI was common in the first year after pediatric SOT and associated with younger age at transplant. All-cause death after RVI was rare, and no definitive attributable death occurred.</p>

10.1093/jpids/piy024

J Pediatric Infect Dis Soc

29538674

A Multicenter Consortium to Define the Epidemiology and Outcomes of Inpatient Respiratory Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.

2018

275-282

2018 Dec 3

2048-7207

<p><strong>Background: </strong>Respiratory virus infections (RVIs) pose a threat to children undergoing hematopoietic stem cell transplantation (HSCT). In this era of sensitive molecular diagnostics, the incidence and outcome of HSCT recipients who are hospitalized with RVI (H-RVI) are not well described.</p>

<p><strong>Methods: </strong>A retrospective observational cohort of pediatric HSCT recipients (between January 2010 and June 2013) was assembled from 9 US pediatric transplant centers. Their medical charts were reviewed for H-RVI events within 1 year after their transplant. An H-RVI diagnosis required respiratory signs or symptoms plus viral detection (human rhinovirus/enterovirus, human metapneumovirus, influenza, parainfluenza, coronaviruses, and/or respiratory syncytial virus). The incidence of H-RVI was calculated, and the association of baseline HSCT factors with subsequent pulmonary complications and death was assessed.</p>

<p><strong>Results: </strong>Among 1560 HSCT recipients, 259 (16.6%) acquired at least 1 H-RVI within 1 year after their transplant. The median age of the patients with an H-RVI was lower than that of patients without an H-RVI (4.8 vs 7.1 years; P &lt; .001). Among the patients with a first H-RVI, 48% required some respiratory support, and 14% suffered significant pulmonary sequelae. The all-cause and attributable case-fatality rates within 3 months of H-RVI onset were 11% and 5.4%, respectively. Multivariate logistic regression revealed that H-RVI onset within 60 days of HSCT, steroid use in the 7 days before H-RVI onset, and the need for respiratory support at H-RVI onset were associated with subsequent morbidity or death.</p>

<p><strong>Conclusion: </strong>Results of this multicenter cohort study suggest that H-RVIs are relatively common in pediatric HSCT recipients and contribute to significant morbidity and death. These data should help inform interventional studies specific to each viral pathogen.</p>

10.1093/jpids/pix051

J Pediatric Infect Dis Soc

29106589