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-August 31, 2021), 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).

of a positive SARS-CoV-2 molecular or rapid antigen detection test result during hospitalization or during the 14 days preceding hospital admission. Demographic data were collected on all COVID-19-associated hospitalizations in 13 states and used to calculate age-stratified hospitalization rates.** Clinical data (signs and symptoms at admission, † † underlying medical conditions, and indicators of severe disease) were available for infants aged <6 months from 12 states. § § Using previously described methods (4), clinical data were collected on all infant COVID-NET cases. Because of the surge in hospitalizations during December 2021 and January 2022, some sites abstracted clinical data on a representative sample of hospitalized infants. ¶ ¶ A birth hospitalization was defined as the hospitalization during which the infant was born.
This analysis describes weekly COVID-19-associated hospitalization rates ( Hospitalization rates from the pre-Delta period and among all other age groups are included for comparison. Average weekly rates and demographic and clinical characteristics of infants aged <6 months were compared across variant-predominant periods. Unadjusted weekly COVID-19-associated hospitalization rates were calculated by dividing the total number of ** Iowa did not collect demographic or clinical data for the full analysis period and was therefore excluded from all analyses. † † Signs and symptoms included respiratory conditions (congestion/runny nose, cough, shortness of breath/respiratory distress, upper respiratory infection, wheezing, nausea/vomiting, rash, and seizures) and nonrespiratory conditions (conjunctivitis, diarrhea, fever, apnea, cyanosis, decreased vocalization/stridor, dehydration, hypothermia, inability to eat/poor feeding, and lethargy). Signs and symptoms were abstracted from medical charts and might be incomplete. § § Maryland provided demographic data for rate calculations but did not collect clinical data for the full analysis period. ¶ ¶ During December 2021-January 2022, sites sampled data for 12%-100% of pediatric patients. Random numbers (1-100) were automatically generated and assigned to each patient on entry into the surveillance database to produce random samples of hospitalized patients for medical record abstraction. Percentages were weighted to account for the probability of selection for sampled patients.
hospitalized patients by population estimates within each age group for the counties included in the surveillance catchment area.*** Because population estimates are available in 1-year age increments, population denominators for hospitalization rates among infants aged <6 months were calculated as one half the population estimate for infants aged <1 year. Three-week moving averages are presented for visualization purposes. Rate ratios (RRs) and 95% CIs were calculated. Demographic characteristics, clinical outcomes, and severity across SARS-CoV-2 variant-predominant periods were compared; the Omicron BA.2-and BA.5-predominant periods were combined in analyses because of small sample sizes. During the combined Omicron BA.2/BA.5-predominant period, the proportions of hospitalized infants with underlying medical conditions and symptoms on admission by age group (<1 month, 1-3 months, 4-5 months) were estimated. Wilcoxon rank-sum tests and chi-square tests were used to compare medians and proportions, respectively; p-values <0.05 were considered statistically significant. Percentages were weighted to account for the probability of selection for sampled cases, and further adjusted to account for nonresponse (i.e., an incomplete chart review). Data were analyzed using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy. † † † During the Omicron BA.2/BA.5-predominant period, the weekly hospitalization rate among infants aged <6 months increased elevenfold (95% CI = 4.3-33.3) from a nadir of 2.2 (week ending April 9, 2022) to a peak of 26.0 (week ending July 23, 2022) and began to decline thereafter ( Figure). The mean weekly hospitalization rate in this group was higher during the Omicron BA.2/BA.5 period (13.7) than during the Delta period (8.3) (RR = 1.6; 95% CI = 1.4-1.8). Compared with the Delta period, rates were also higher during the BA.2/BA.5 period among infants and children aged 6 months-4 years (RR = 1.9) and adults aged ≥75 years (RR = 1.4) but lower among children and adolescents aged 5-17 years (RR = 0.9), adults aged 18-64 years (RR = 0.5), and adults aged 65-74 years (RR = 0.8). The mean weekly hospitalization rate among infants aged <6 months during the Omicron BA.2/BA.5 period (13.7) was less than that of adults aged ≥75 years (39.4), similar to that of adults aged 65-74 years (13.8) and higher than rates in all other pediatric age groups (2.3 and 0.8 for children aged 6-23 months and 2-4 years, respectively) and in adults aged <65 years (4,6). Complete clinical data were available for 1,116 infants aged <6 months hospitalized with laboratory-confirmed COVID-19, including 321, 322, and 473 infants hospitalized during the Delta, Omicron BA.1, and Omicron BA.2/BA.5 periods, respectively (Table 1). Differences during the three periods were small, and not all were statistically significant; however, indicators of severity, including length of hospital stay, and the proportion of hospitalizations that required intensive care unit admission, high-flow nasal cannula, mechanical ventilation, or bilevel positive airway pressure/continuous positive airway pressure (BiPAP/CPAP) were consistently lower during the Omicron BA.2/BA.5 period than during the Delta period, and in-hospital deaths were rare (<1%).

Discussion
Compared with the Delta variant-predominant period, COVID-19-associated hospitalization rates increased among infants aged <6 months during Omicron variant-predominant periods, but the proportion of hospitalized infants aged <6 months with indicators of the most severe illness did not increase. Among infants aged <6 months, the average weekly COVID-19-associated hospitalization rate during the SARS-CoV-2 Omicron BA.2/BA.5 variant-predominant period was similar to that among adults aged 65-74 years and higher than that in other pediatric age groups and younger adults. These findings underscore the continued risk for COVID-19-associated hospitalization among infants aged <6 months, who are ineligible for vaccination.
Multiple factors likely contributed to high COVID-19associated hospitalization rates among young infants during the Omicron variant-predominant period, including the high infectivity and community transmission of the SARS-CoV-2 Omicron variant and the relatively low threshold for hospitalizing infants for signs and symptoms consistent with COVID-19 (e.g., fever) relative to that in older children (7).

TABLE 1. Demographic characteristics and clinical outcomes of hospitalized infants aged <6 months with laboratory-confirmed SARS-CoV-2 infections,* by period of SARS-CoV-2 variant predominance -Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, 12 states, † June 20, 2021-August 31, 2022
Characteristic 2-dose primary monovalent mRNA COVID-19 vaccination series during pregnancy has been estimated to be 52% effective against COVID-19 hospitalization among infants aged <6 months. This suggests that young infants might receive protection through passive transplacental transfer of maternal antibodies acquired through maternal vaccination. Effectiveness of maternal vaccination in preventing disease in young infants was lower during the early Omicron variantpredominant period (38%) than during the Delta variantpredominant period (80%) (9). Surveillance data show that compared with earlier periods, during the recent Omicron variant-predominant periods, a larger proportion of pregnant women received a vaccination series before pregnancy (9,10). Because of immune evasion when novel variants have emerged and waning immunity as time since the last dose increases, infants born during the Omicron BA.5 variant-predominant period might have had less protection. The findings in this report are subject to at least five limitations. First, population estimates for infants aged <6 months were not available; therefore, the assumption was that they accounted for one half of infants aged <1 year when calculating rates. This assumption does not account for seasonality in births, † † † † which was affected by the pandemic; births typically peak in the summer, leading to potential small overestimates of rates during Omicron BA.2/BA.5 variant-predominant periods. Second, it was not possible to account for changes in public health policies and testing and treatment practices over time. Third, maternal vaccination or previous infection, which might confer some immunity to infants, was not assessed. Fourth, periods of variant predominance are based on national data and might not reflect regional differences in circulating variants. Finally, the COVID-NET catchment areas include approximately 10% of the U.S. population; these findings might not be nationally generalizable.

SARS-CoV-2 variant predominance period, no. (%) of hospitalizations
Although these findings do not suggest increased severity of COVID-19 among hospitalized infants, COVID-19associated hospitalization rates in infants aged <6 months A birth hospitalization was defined as the hospitalization during which the infant was born. ¶ Defined as one or more of the following: prematurity, neurologic disorders, congenital heart disease, abnormality of airway, chronic metabolic disease, immunocompromised condition, chronic lung disease of prematurity/bronchopulmonary dysplasia, or asthma/reactive airway disease. Underlying conditions that occurred in fewer than five sampled cases in any stratum are not displayed. ** COVID-19-related signs and symptoms included respiratory conditions (congestion/runny nose, cough, shortness of breath/respiratory distress, upper respiratory infection, wheezing, nausea/vomiting, rash, and seizures) and nonrespiratory conditions (conjunctivitis, diarrhea, fever/chills, apnea, cyanosis, decreased vocalization/ stridor, dehydration, hypothermia, inability to eat/poor feeding, and lethargy). Signs and symptoms were abstracted from medical charts and might be incomplete. † † Symptoms that occurred in fewer than five sampled cases in any stratum are not displayed. § § Relative SE >30%

Summary
What is already known about this topic?
Infants aged <6 months, who are ineligible for vaccination, have high COVID-19-associated hospitalization rates compared with other pediatric age groups.
What is added by this report?
Although population-based COVID-19-associated hospitalization rates among infants aged <6 months increased in the Omicron variant-predominant periods compared with the Delta variantpredominant period, indicators of the most severe disease among hospitalized infants aged <6 months did not.
What are the implications for public health practice?
Pregnant women should stay up to date with COVID-19 vaccination to help protect themselves and infants too young to be vaccinated. Nonpharmaceutical measures should be used to help protect infants ineligible for vaccination.
were higher during the Omicron variant-predominant periods (December 2021-August 2022) than they were during previous periods. Maternal vaccination has been shown to provide protection to infants aged <6 months who are currently ineligible for vaccination (9), and both CDC and the American College of Obstetricians and Gynecologists recommend COVID-19 vaccination for women who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future. § § § § COVID-19 hospitalization rates in infants aged <6 months are higher than those of all other age groups except adults aged ≥65 years. To help protect both pregnant women and infants too young to be vaccinated, prevention should focus on ensuring that pregnant women stay up to date on COVID-19 vaccines ¶ ¶ ¶ ¶ (including receiving a bivalent booster dose)***** § § § § h t t p s : / / w w w. c d c . g o v / c o r o n a v i r u s / 2 0 1 9 -n c o v / v a c c i n e s / recommendations/pregnancy.html; https://www.acog.org/ clinical/clinical-guidance/practice-advisory/articles/2020/12/ covid-19-vaccination-considerations-for-obstetric-gynecologic-care ¶ ¶ ¶ ¶ https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/ pregnancy.html ***** https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interimconsiderations-us.html and implementing nonpharmaceutical interventions for COVID-19 prevention (6) and newborn care. † † † † †