Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants.

BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

Risk of Hospitalization and Mortality Following Medically Attended Norovirus Infection-Veterans Health Administration, 2010-2018.

Background: While prior studies have suggested a role for norovirus gastroenteritis in contributing to severe morbidity and mortality, the importance of norovirus as a causal pathogen for hospitalization and mortality remains poorly understood. We estimated the effect of laboratory-confirmed norovirus infection on hospitalization and mortality among a national cohort of veterans who sought care within the Veterans Affairs health care system. Methods: We analyzed electronic health record data from a cohort study of adults who were tested for norovirus within the Veterans Affairs system between 1 January 2010 and 31 December 2018. Adjusted risk ratios (aRRs) for hospitalization and mortality were estimated using log-binomial regression models, adjusting for age, Clostridioides difficile, underlying medical conditions, and nursing home residence. Results: In total, 23 196 veterans had 25 668 stool samples tested for norovirus; 2156 samples (8.4%) tested positive. Testing positive for norovirus infection, compared with testing negative, was associated with a slight increased risk of hospitalization (aRR, 1.13 [95% confidence interval, 1.06-1.21]) and a significant increased risk of mortality within 3 days after the norovirus test (2.14 [1.10-4.14]). The mortality aRR within 1 week and 1 month were reduced to 1.40 (95% confidence interval, .84-2.34) and 0.97 (.70-1.35), respectively. Conclusions: Older veterans with multiple comorbid conditions were at a slight increased risk of hospitalization and significant increased risk of mortality in the 3 days after a norovirus-positive test, compared with those testing negative. Clinicians should be aware of these risks and can use these data to inform clinical management for veterans with norovirus.

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

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 log10 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.

Risk Factors for Acute Gastroenteritis Among Patients Hospitalized in 5 Veterans Affairs Medical Centers, 2016-2019.

Background: In the United States, ∼179 million acute gastroenteritis (AGE) episodes occur annually. We aimed to identify risk factors for all-cause AGE, norovirus-associated vs non-norovirus AGE, and severe vs mild/moderate AGE among hospitalized adults. Methods: We enrolled 1029 AGE cases and 624 non-AGE controls from December 1, 2016, to November 30, 2019, at 5 Veterans Affairs Medical Centers. Patient interviews and medical chart abstractions were conducted, and participant stool samples were tested using the BioFire Gastrointestinal Panel. Severe AGE was defined as a modified Vesikari score of ≥11. Multivariate logistic regression was performed to assess associations between potential risk factors and outcomes; univariate analysis was conducted for norovirus-associated AGE due to limited sample size. Results: Among 1029 AGE cases, 551 (54%) had severe AGE and 44 (4%) were norovirus positive. Risk factors for all-cause AGE included immunosuppressive therapy (adjusted odds ratio [aOR], 5.6; 95% CI, 2.7-11.7), HIV infection (aOR, 3.9; 95% CI, 1.8-8.5), severe renal disease (aOR, 3.1; 95% CI, 1.8-5.2), and household contact with a person with AGE (aOR, 2.9; 95% CI, 1.3-6.7). Household (OR, 4.4; 95% CI, 1.6-12.0) and non-household contact (OR, 5.0; 95% CI, 2.2-11.5) with AGE was associated with norovirus-associated AGE. Norovirus positivity (aOR, 3.4; 95% CI, 1.3-8.8) was significantly associated with severe AGE. Conclusions: Patients with immunosuppressive therapy, HIV, and severe renal disease should be monitored for AGE and may benefit from targeted public health messaging regarding AGE prevention. These results may also direct future public health interventions, such as norovirus vaccines, to specific high-risk populations.

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

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 10 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: Question: 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?Findings: 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.Meaning: COVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.

Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol.

BACKGROUND: Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. METHODS: The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. DISCUSSION: Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. TRIAL REGISTRATION: NCT05031468 .

Association of Secretor Status and Recent Norovirus Infection With Gut Microbiome Diversity Metrics in a Veterans Affairs Population.

Norovirus infection causing acute gastroenteritis could lead to adverse effects on the gut microbiome. We assessed the association of microbiome diversity with norovirus infection and secretor status in patients from Veterans Affairs medical centers. Alpha diversity metrics were lower among patients with acute gastroenteritis but were similar for other comparisons.

Enteric Illness Outbreaks Reported Through the National Outbreak Reporting System-United States, 2009-2019.

BACKGROUND: The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. This study describes enteric illness outbreaks reported during 11 years of surveillance. METHODS: We extracted finalized reports from NORS for outbreaks occurring during 2009-2019. Outbreaks were included if caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. RESULTS: A total of 38 395 outbreaks met inclusion criteria, increasing from 1932 in 2009 to 3889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n = 23 812; 62%) and contaminated food (n = 9234; 24%). Norovirus was the most commonly reported etiology, reported in 22 820 (59%) outbreaks, followed by Salmonella (n = 2449; 6%) and Shigella (n = 1171; 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (P < .0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and Escherichia coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). Case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). CONCLUSIONS: Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.

Adapting the Surveillance Platform for Enteric and Respiratory Infectious Organisms at United States Veterans Affairs Medical Centers (SUPERNOVA) for COVID-19 Among Hospitalized Adults: Surveillance Protocol.

Introduction: Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) rapidly initiated COVID-19 surveillance by leveraging existing hospital networks to assess disease burden among hospitalized inpatients and inform prevention efforts. Materials and Methods: The Surveillance Platform for Enteric and Respiratory Infectious Organisms at Veterans Affairs Medical Centers (SUPERNOVA) is a network of five United States Veterans Affairs Medical Centers which serves nearly 400,000 Veterans annually and conducts laboratory-based passive and active monitoring for pathogens associated with acute gastroenteritis and acute respiratory illness among hospitalized Veterans. This paper presents surveillance methods for adapting the SUPERNOVA surveillance platform to prospectively evaluate COVID-19 epidemiology during a public health emergency, including detecting, characterizing, and monitoring patients with and without COVID-19 beginning in March 2020. To allow for case-control analyses, patients with COVID-19 and patients with non-COVID-19 acute respiratory illness were included. Results: SUPERNOVA included 1,235 participants with COVID-19 and 707 participants with other acute respiratory illnesses hospitalized during February through December 2020. Most participants were male (93.1%), with a median age of 70 years, and 45.8% non-Hispanic Black and 32.6% non-Hispanic White. Among those with COVID-19, 28.2% were transferred to an intensive care unit, 9.4% received invasive mechanical ventilation, and 13.9% died. Compared with controls, after adjusting for age, sex, and race/ethnicity, COVID-19 case-patients had significantly higher risk of mortality, respiratory failure, and invasive mechanical ventilation, and longer hospital stays. Discussion: Strengths of the SUPERNOVA platform for COVID-19 surveillance include the ability to collect and integrate multiple types of data, including clinical and illness outcome information, and SARS-CoV-2 laboratory test results from respiratory and serum specimens. Analysis of data from this platform also enables formal comparisons of participants with and without COVID-19. Surveillance data collected during a public health emergency from this key U.S. population of Veterans will be useful for epidemiologic investigations of COVID-19 spectrum of disease, underlying medical conditions, virus variants, and vaccine effectiveness, according to public health priorities and needs.