Vaccination Status and Trends in Adult COVID-19-Associated Hospitalizations by Race and Ethnicity, March 2020-August 2022.

BACKGROUND: We sought to evaluate whether race/ethnicity disparities in severe COVID-19 outcomes persist in the era of vaccination. METHODS: Population-based age-adjusted monthly rate ratios (RR) of laboratory-confirmed COVID-19-asssociated hospitalizations were calculated among adult patients from COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) during March 2020 - August 2022, by race/ethnicity. Among randomly sampled patients, July 2021-August 2022, RRs for hospitalization, intensive care unit (ICU) admission, and in-hospital mortality were calculated for Hispanic, Black, American Indian/Alaskan Native (AI/AN), and Asian/Pacific Islander (API) versus White persons. RESULTS: Based on data from 353,807 hospitalized patients, hospitalization rates were higher among Hispanic, Black and AI/AN versus White persons during March 2020 - August 2022, yet the magnitude of the disparities declined over time (for Hispanic, RR=6.7; 95%CI: 6.5-7.1 in June 2020 vs RR<2.0 after July 2021; for AI/AN, RR=8.4; 95%CI: 8.2-8.7in May 2020 vs RR<2.0 after March 2022; and for Black persons RR=5.3; 95%CI: 4.6-4.9 in July 2020 vs RR<2.0 after February 2022; all p≤0.001). Among 8,706 sampled patients during July 2021 - August 2022, hospitalization and ICU admission RRs were higher for Hispanic, Black, and AI/AN (range for both hospitalization and ICU admission: 1.4-2.4) and lower for API (range for both: 0.6-0.9) versus White persons. All other race and ethnicity groups had higher in-hospital mortality rates versus White persons (RR range: 1.4-2.9). CONCLUSIONS: Race/ethnicity disparities in COVID-19-associated hospitalizations declined but persist in the era of vaccination. Developing strategies to ensure equitable access to vaccination and treatment remains important.

Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multi-organ involvement in MIS-C encompassing diverse cell types including endothelial and neuronal cells, and an enrichment of pyroptosis related genes. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers. Graphical Loy et al. use cell-free RNA, whole blood RNA, and cell-free DNA sequencing to characterize distinct host response and cellular injury profiles in pediatric patients with MIS-C and/or COVID-19. This study highlights the complementary information from cell-free and whole blood RNA analyses, with broad implications for future liquid biopsy applications.

Longitudinal Neutralizing and Functional Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants Following Messenger RNA Coronavirus Disease 2019 Vaccination.

In this longitudinal prospective cohort of healthy adults in the United States, we found that coronavirus disease 2019 messenger RNA primary series and booster vaccinations elicited high titers of broadly cross-reactive neutralizing and antibody-dependent cell-mediated cytotoxicity antibodies, which gradually waned over 6 months, particularly against severe acute respiratory syndrome coronavirus 2 variants. These data support the indication for a subsequent booster vaccination.

Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C)

Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n=16) and children with history of MIS-C (n=7) or COVID-19 (n=8). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were significantly reduced to the Omicron variant.

Bacterial and viral infections among adults hospitalized with COVID‐19, COVID‐NET, 14 states, March 2020–April 2022

Background Bacterial and viral infections can occur with SARS‐CoV‐2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods We used the Coronavirus Disease 2019‐Associated Hospitalization Surveillance Network (COVID‐NET), a population‐based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory‐confirmed SARS‐CoV‐2 infection between March 2020 and April 2022. Clinician‐driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. We also describe the prevalence of viral pathogens including respiratory syncytial virus, rhinovirus/enterovirus, influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and non‐SARS‐CoV‐2 endemic coronaviruses. Results Among 36 490 hospitalized adults with COVID‐19, 53.3% had bacterial cultures taken within 7 days of admission and 6.0% of these had a clinically relevant bacterial pathogen. After adjustment for demographic factors and co‐morbidities, bacterial infections in patients with COVID‐19 within 7 days of admission were associated with an adjusted relative risk of death 2.3 times that of patients with negative bacterial testing. Staphylococcus aureus and Gram‐negative rods were the most frequently isolated bacterial pathogens. Among hospitalized adults with COVID‐19, 2766 (7.6%) were tested for seven virus groups. A non‐SARS‐CoV‐2 virus was identified in 0.9% of tested patients. Conclusions Among patients with clinician‐driven testing, 6.0% of adults hospitalized with COVID‐19 were identified to have bacterial coinfections and 0.9% were identified to have viral coinfections;identification of a bacterial coinfection within 7 days of admission was associated with increased mortality.

Acute Cardiac Events During COVID-19-Associated Hospitalizations.

BACKGROUND: COVID-19 is associated with cardiac complications. OBJECTIVES: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. METHODS: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. RESULTS: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. CONCLUSIONS: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization.

Serologic responses to COVID-19 vaccination in children with history of multisystem inflammatory syndrome (MIS-C).

Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n = 16) and children with history of MIS-C (n = 7) or COVID-19 (n = 8). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were significantly reduced to the Omicron variant.

Multiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19.

The pathogenesis of multi-organ dysfunction associated with severe acute SARS-CoV-2 infection remains poorly understood. Endothelial damage and microvascular thrombosis have been identified as drivers of COVID-19 severity, yet the mechanisms underlying these processes remain elusive. Here we show alterations in fluid shear stress-responsive pathways in critically ill COVID-19 adults as compared to non-COVID critically ill adults using a multiomics approach. Mechanistic in-vitro studies, using microvasculature-on-chip devices, reveal that plasma from critically ill COVID-19 adults induces fibrinogen-dependent red blood cell aggregation that mechanically damages the microvascular glycocalyx. This mechanism appears unique to COVID-19, as plasma from non-COVID sepsis patients demonstrates greater red blood cell membrane stiffness but induces less significant alterations in overall blood rheology. Multiomics analyses in pediatric patients with acute COVID-19 or the post-infectious multi-inflammatory syndrome in children (MIS-C) demonstrate little overlap in plasma cytokine and metabolite changes compared to adult COVID-19 patients. Instead, pediatric acute COVID-19 and MIS-C patients show alterations strongly associated with cytokine upregulation. These findings link high fibrinogen and red blood cell aggregation with endotheliopathy in adult COVID-19 patients and highlight differences in the key mediators of pathogenesis between adult and pediatric populations.

Bacterial and viral infections among adults hospitalized with COVID-19, COVID-NET, 14 states, March 2020-April 2022.

Background: Bacterial and viral infections can occur with SARS-CoV-2 infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods: We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system, to investigate the occurrence of bacterial and viral infections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection between March 2020 and April 2022. Clinician-driven testing for bacterial pathogens from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. We also describe the prevalence of viral pathogens including respiratory syncytial virus, rhinovirus/enterovirus, influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and non-SARS-CoV-2 endemic coronaviruses. Results: Among 36 490 hospitalized adults with COVID-19, 53.3% had bacterial cultures taken within 7 days of admission and 6.0% of these had a clinically relevant bacterial pathogen. After adjustment for demographic factors and co-morbidities, bacterial infections in patients with COVID-19 within 7 days of admission were associated with an adjusted relative risk of death 2.3 times that of patients with negative bacterial testing. Staphylococcus aureus and Gram-negative rods were the most frequently isolated bacterial pathogens. Among hospitalized adults with COVID-19, 2766 (7.6%) were tested for seven virus groups. A non-SARS-CoV-2 virus was identified in 0.9% of tested patients. Conclusions: Among patients with clinician-driven testing, 6.0% of adults hospitalized with COVID-19 were identified to have bacterial coinfections and 0.9% were identified to have viral coinfections; identification of a bacterial coinfection within 7 days of admission was associated with increased mortality.

Vaccine Attitudes and COVID-19 Vaccine Intention Among Parents of Children With Kidney Disease or Primary Hypertension.

RATIONALE & OBJECTIVE: Children with kidney disease and primary hypertension may be more vulnerable to COVID-19. We examined COVID-19 vaccine hesitancy among parents of children with chronic kidney disease or hypertension. STUDY DESIGN: Sequential explanatory mixed-methods design; survey followed by in-depth interviews. SETTING & PARTICIPANTS: Parents of children aged <18 years with kidney disease or primary hypertension within a large pediatric practice. EXPOSURE: Parental attitudes toward general childhood and influenza vaccines assessed by the Vaccine Hesitancy Scale. Kidney disease classification, demographic and socioeconomic factors, experiences with COVID-19, COVID-19 mitigation activities and self-efficacy, and sources of vaccine information. OUTCOME: Willingness to vaccinate child against COVID-19. ANALYTICAL APPROACH: Analysis of variance (ANOVA) test to compare parental attitudes toward general childhood and influenza vaccination with attitudes toward COVID-19 vaccination. Multinomial logistic regression to assess predictors of willingness to vaccinate against COVID-19. Thematic analysis of interview data to characterize influences on parental attitudes. RESULTS: Of the participants, 207 parents completed the survey (39% of approached): 75 (36%) were willing, 80 (39%) unsure, and 52 (25%) unwilling to vaccinate their child against COVID-19. Hesitancy toward general childhood and influenza vaccines was highest among the unwilling group (P < 0.001). More highly educated parents more likely to be willing to vaccinate their children, while Black race was associated with being more likely to be unwilling. Rushed COVID-19 vaccine development as well as fear of serious and unknown long-term side effects were themes that differed across the parental groups that were willing, unsure, or unwilling to vaccinate their children. Although doctors and health care teams are trusted sources of vaccine information, perceptions of benefit versus harm and experiences with doctors differed among these 3 groups. The need for additional information on COVID-19 vaccines was greatest among those unwilling or unsure about vaccinating. LIMITATIONS: Generalizability may be limited. CONCLUSIONS: Two-thirds of parents of children with kidney disease or hypertension were unsure or unwilling to vaccinate their child against COVID-19. Higher hesitancy toward routine childhood and influenza vaccination was associated with hesitancy toward COVID-19 vaccines. Enhanced communication of vaccine information relevant to kidney patients in an accessible manner should be examined as a means to reduce vaccine hesitancy. PLAIN-LANGUAGE SUMMARY: Children with kidney disease or hypertension may do worse with COVID-19. As there are now effective vaccines to protect children from COVID-19, we wanted to find out what parents think about COVID-19 vaccines and what influences their attitudes. We surveyed and then interviewed parents of children who had received a kidney transplant, were receiving maintenance dialysis, had chronic kidney disease, or had hypertension. We found that two-thirds of parents were hesitant to vaccinate their children. Their reasons varied, but the key issues included the need for information pertinent to their child and a consistent message from doctors and other health care providers. These findings may inform an effective vaccine campaign to protect children with kidney disease and hypertension.

Codetections of Other Respiratory Viruses Among Children Hospitalized With COVID-19.

OBJECTIVES: To assess the clinical impact of respiratory virus codetections among children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: During March 2020 to February 2022, the US coronavirus disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) identified 4372 children hospitalized with SARS-CoV-2 infection admitted primarily for fever, respiratory illness, or presumed COVID-19. We compared demographics, clinical features, and outcomes between those with and without codetections who had any non-SARS-CoV-2 virus testing. Among a subgroup of 1670 children with complete additional viral testing, we described the association between presence of codetections and severe respiratory illness using age-stratified multivariable logistic regression models. RESULTS: Among 4372 children hospitalized, 62% had non-SARS-CoV-2 respiratory virus testing, of which 21% had a codetection. Children with codetections were more likely to be <5 years old (yo), receive increased oxygen support, or be admitted to the ICU (P < .001). Among children <5 yo, having any viral codetection (<2 yo: adjusted odds ratio [aOR] 2.1 [95% confidence interval [CI] 1.5-3.0]; 2-4 yo: aOR 1.9 [95% CI 1.2-3.1]) or rhinovirus/enterovirus codetection (<2 yo: aOR 2.4 [95% CI 1.6-3.7]; 2-4: aOR 2.4 [95% CI 1.2-4.6]) was significantly associated with severe illness. Among children <2 yo, respiratory syncytial virus (RSV) codetections were also significantly associated with severe illness (aOR 1.9 [95% CI 1.3-2.9]). No significant associations were seen among children ≥5 yo. CONCLUSIONS: Respiratory virus codetections, including RSV and rhinovirus/enterovirus, may increase illness severity among children <5 yo hospitalized with SARS-CoV-2 infection.

Subgenomic RNA Abundance Relative to Total Viral RNA Among Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subgenomic RNA (sgRNA) may indicate actively replicating virus, but sgRNA abundance has not been systematically compared between SARS-CoV-2 variants. sgRNA was quantified in 169 clinical samples by real-time reverse-transcription polymerase chain reaction, demonstrating similar relative abundance among known variants. Thus, sgRNA detection can identify individuals with active viral replication regardless of variant.

Update From the September 2022 Meeting of the Advisory Committee on Immunization Practices.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides expert advice to the Centers for Disease Control and Prevention (CDC), normally meets three times per year to develop US vaccine recommendations. The ACIP increased their meeting frequency over the past 2.5 years to address vaccine-related issues during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. They met to discuss updating COVID-19 booster dose recommendations on September 1, 2022 recommending use of new bivalent Coronavirus Disease-2019 (COVID-19) booster vaccines which include equal amounts of ancestral and Omicron BA.4/BA.5 variant mRNA that encodes the spike protein.

Comparison of influenza and COVID-19-associated hospitalizations among children < 18 years old in the United States-FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021).

BACKGROUND: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. METHODS: Influenza and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, two population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (October 1, 2020-September 30, 2021) was compared to influenza-associated hospitalization rates during the 2017-18 through 2019-20 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. RESULTS: Among children <18 years old, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-18 (33.5), 2018-19 (33.8), and 2019-20 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years old, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; p < 0.01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; p = 0.28). CONCLUSIONS: In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years old compared with influenza during the three seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses.

SARS-CoV-2 Antigenemia is Associated With Pneumonia in Children But Lacks Sensitivity to Diagnose Acute Infection.

BACKGROUND: Nucleocapsid antigenemia in adults has demonstrated high sensitivity and specificity for acute infection, and antigen burden is associated with disease severity. Data regarding SARS-CoV-2 antigenemia in children are limited. METHODS: We retrospectively analyzed blood plasma specimens from hospitalized children with COVID-19 or MIS-C. Nucleocapsid and spike were measured using ultrasensitive immunoassays. RESULTS: We detected nucleocapsid antigenemia in 62% (50/81) and spike antigenemia in 27% (21/79) of children with acute COVID-19 but 0% (0/26) and 15% (4/26) with MIS-C from March 2020-March 2021. Higher nucleocapsid levels were associated with radiographic infiltrates and respiratory symptoms in children with COVID-19. CONCLUSIONS: Antigenemia lacks the sensitivity to diagnose acute infection in children but is associated with signs and symptoms of lower respiratory tract involvement. Further study into the mechanism of antigenemia, its association with specific organ involvement, and the role of antigenemia in the pathogenesis of COVID-19 is warranted.

Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza - United States, 2021-22 Influenza Season.

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.

COVID-19-Associated Hospitalizations Among U.S. Infants Aged <6 Months - COVID-NET, 13 States, June 2021-August 2022.

COVID-19-associated hospitalization rates are highest among adults aged ≥65 years (1); however, COVID-19 can and does cause severe and fatal outcomes in children, including infants (2,3). After the emergence of the SARS-CoV-2 B.1.1.529 (Omicron) BA.1 variant in December 2021, hospitalizations among children aged <5 years, who were ineligible for vaccination, increased more rapidly than did those in other age groups (4). On June 18, 2022, CDC recommended COVID-19 vaccination for infants and children aged ≥6 months (5). Data from the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)* were analyzed to describe changes in the age distribution of COVID-19-associated hospitalizations since the Delta-predominant period (June 20-December 18, 2021)^† with a focus on U.S. infants aged <6 months. During the Omicron BA.2/BA.5-predominant periods (December 19, 2021­August 31, 2022), weekly hospitalizations per 100,000 infants aged <6 months increased from a nadir of 2.2 (week ending April 9, 2022) to a peak of 26.0 (week ending July 23, 2022), and the average weekly hospitalization rate among these infants (13.7) was similar to that among adults aged 65-74 years (13.8). However, the prevalence of indicators of severe disease^§ among hospitalized infants did not increase since the B.1.617.2 (Delta)-predominant period. To help protect infants too young to be vaccinated, prevention should focus on nonpharmaceutical interventions and vaccination of pregnant women, which might provide protection through transplacental transfer of antibodies (6).

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).