While costs of norovirus acute gastroenteritis (AGE) to healthcare systems have been estimated, out-of-pocket and indirect costs incurred by households are not well documented in community settings, particularly in developing countries. We conducted active surveillance for AGE in two communities in Peru: Puerto Maldonado (October 2012-August 2015) and San Jeronimo (April 2015-April 2019). Norovirus AGE events with PCR-positive stool specimens were included. Data collected in follow-up interviews included event-related medical resource utilization, associated out-of-pocket costs, and indirect costs. There were 330 norovirus-associated AGE events among 3,438 participants from 685 households. Approximately 49% of norovirus events occurred among children <5 years of age and total cost to the household per episode was highest in this age group. Norovirus events cost a median of US $2.95 (IQR $1.04-7.85) in out-of-pocket costs and $12.58 (IQR $6.39-25.16) in indirect costs. Medication expenses accounted for 53% of out-of-pocket costs, and productivity losses accounted for 59% of the total financial burden on households. The frequency and associated costs of norovirus events to households in Peruvian communities support the need for prevention strategies including vaccines. Norovirus interventions targeting children <5 years of age and their households may have the greatest economic benefit.

BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None.

Background As of August 21, 2021, &gt;60% of the U.S. population aged ≥18 years were fully vaccinated with vaccines highly effective in preventing hospitalization due to Coronavirus Disease-2019 (COVID-19). Infection despite full vaccination (vaccine breakthrough) has been reported, but characteristics of those with vaccine breakthrough resulting in hospitalization and relative rates of hospitalization in unvaccinated and vaccinated persons are not well described, including during late June and July 2021 when the highly transmissible Delta variant predominated.Methods From January 1–June 30, 2021, cases defined as adults aged ≥18 years with laboratory-confirmed Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection were identified from &gt;250 acute care hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network (COVID-NET). Through chart review for sampled cases, we examine characteristics associated with vaccination breakthrough. From January 24–July 24, 2021, state immunization information system data linked to both &gt;37,000 cases representative cases and the defined surveillance catchment area population were used to compare weekly hospitalization rates in vaccinated and unvaccinated individuals. Unweighted case counts and weighted percentages are presented.Results From January 1 – June 30, 2021, fully vaccinated cases increased from 1 (0.01%) to 321 (16.1%) per month. Among 4,732 sampled cases, fully vaccinated persons admitted with COVID-19 were older compared with unvaccinated persons (median age 73 years [Interquartile Range (IQR) 65-80] v. 59 years [IQR 48-70]; p&lt;0.001), more likely to have 3 or more underlying medical conditions (201 (70.8%) v. 2,305 (56.1%), respectively; p&lt;0.001) and be residents of long-term care facilities [37 (14.5%) v. 146 (5.5%), respectively; p&lt;0.001]. From January 24 – July 24, 2021, cumulative hospitalization rates were 17 times higher in unvaccinated persons compared with vaccinated persons (423 cases per 100,000 population v. 26 per 100,000 population, respectively); rate ratios were 23, 22 and 13 for those aged 18-49, 50-64, and ≥65 years respectively. For June 27 – July 24, hospitalization rates were ≥10 times higher in unvaccinated persons compared with vaccinated persons for all age groups across all weeks.Conclusion Population-based hospitalization rates show that unvaccinated adults aged ≥18 years are 17 times more likely to be hospitalized compared with vaccinated adults. Rates are far higher in unvaccinated persons in all adult age groups, including during a period when the Delta variant was the predominant strain of the SARS-CoV-2 virus. Vaccines continue to play a critical role in preventing serious COVID-19 illness and remain highly effective in preventing COVID-19 hospitalizations.Competing Interest StatementAll authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Evan J. Anderson reports grants from Pfizer, grants from Merck, grants from PaxVax, grants from Micron, grants from Sanofi-Pasteur, grants from Janssen, grants from MedImmune, grants from GSK, personal fees from Sanofi-Pasteur, personal fees from Pfizer, personal fees from Medscape, personal fees from Kentucky Bioprocessing, Inc, personal fees from Sanofi-Pasteur, personal fees from Janssen, outside the submitted work; and his institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Ruth Lynfield reports Associate Editor for American Academy of Pediatrics Red Book (Committee on Infectious Diseases), donated fee to Minnesota Department of Health. Laurie M. Billing reports grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study; grants from Centers for Disease Control and Prevention (CDC) outside the submitted work. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. No other potential conflicts of interest were disclosed.Funding StatementThis work was supported by the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement (grant CK17-1701) and through a Council of State and Territorial Epidemiologists cooperative agreement (grant NU38OT000297-02-00).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (see e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesPublicly available data referred to in this analysis can be found at: https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html https://gis.cdc.gov/grasp/covidnet/covid19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html

Importance The impact of non-pharmaceutical interventions (NPIs) in response to the SARS-CoV-2 pandemic on incidence of other infectious diseases is still being assessed.Objective To determine if the observed change in reported norovirus outbreaks in the United States was best explained by underreporting, seasonal trends, or reduced exposure due to NPIs. We also aimed to assess if the change in reported norovirus outbreaks varied by setting.Design An ecologic, interrupted time series analysis of norovirus outbreaks from nine states reported to the National Outbreak Reporting System (NORS) from July 2012–July 2020.Setting Surveillance data from Massachusetts, Michigan, Minnesota, Ohio, Oregon, South Carolina, Tennessee, Virginia, and Wisconsin were included in the analysis.Participants 9,226 reports of acute gastroenteritis outbreaks with norovirus as an epidemiologically suspected or laboratory-confirmed etiology were included in the analysis, resulting in more than 8 years of follow up. Outbreak reports from states that participated in NoroSTAT for at least 4 years were included in the analysis (range: 4–8 years).Exposure The main exposure of interest was time period: before (July 2012–February 2020) or after (April 2020–July 2020) the start of NPIs in the United StatesMain outcome The main outcome of interest was monthly rate of reported norovirus outbreaks. As a secondary outcome, we also examined the average outbreak size.Results We found that the decline in norovirus outbreak reports was significant for all 9 states considered (pooled incidence rate ratio (IRR) comparing April 2020-July 2020 vs. all pre-COVID months for each state= 0.14, 95% CI: 0.098, 0.21; P=&lt;0.0001), even after accounting for typical seasonal decline in incidence during the summer months. These patterns were similar across a variety of settings, including nursing homes, child daycares, healthcare settings, and schools. The average outbreak size was also reduced by 61% (95% CI: 56%, 42.7%; P=&lt;0.0001), suggesting that the decline does not reflect a tendency to report only more severe outbreaks due to strained surveillance systems, but instead reflects a decline in incidence.Conclusions and relevance While NPIs implemented during the spring and summer of 2020 were intended to reduce transmission of SARS-CoV-2, these changes also appear to have impacted the incidence of norovirus, a non-respiratory pathogen. These results suggest that NPIs may provide benefit for preventing transmission of other human pathogens, reducing strain to health systems during the continued SARS-CoV-2 pandemic.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention (CDC).Competing Interest StatementBAL reports grants and personal fees from Takeda Pharmaceuticals and personal fees from World Health Organization outside the submitted work.Funding StatementBAL and ANMK were supported by NIH/NIGMS (R01 GM124280, R01 GM 12480-03S1) and NSF (2032084).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval to use the data for the present work was provided by the Norovirus Outbreak Reporting System team upon submitting a formal data request. For the present analysis, data were only provided at the outbreak level and no personally identifiable data were used such that the released data meets federal guidelines for ethical compliance in release of surveillance data, as described in the Public Health Service Act. The original data collection is from public health surveillance and is covered by section 301 of the Public Health Service Act (42 USC 241). As a surveillance activity, the initial data collection is considered not to be research with human subjects based on these guidelines.All necessary patient/participa t consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesNorostat data are publicly available at https://www.cdc.gov/norovirus/reporting/norostat/data-table.html. More detailed Norostat data can be obtained by sending a formal data request to the Centers for Disease Control and Prevention at NORSDashboard@cdc.gov. https://www.cdc.gov/norovirus/reporting/norostat/data-table.html

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

BACKGROUND: To reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed. METHODS: We fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012-2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022-2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels. RESULTS: We found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70-90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70-90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection. CONCLUSIONS: These results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses.

Norovirus is the most common cause of gastroenteritis outbreaks in long-term care facilities (LTCFs) in the United States, causing a high burden of disease in both residents and staff. Understanding how case symptoms and characteristics contribute to norovirus transmission can lead to more informed outbreak control measures in LTCFs. We examined line lists for 107 norovirus outbreaks that took place in LTCFs in five U.S. states from 2015 to 2019. We estimated the individual effective reproduction number, R(i), to quantify individual case infectiousness and examined the contribution of vomiting, diarrhea, and being a resident (vs. staff) to case infectiousness. The associations between case characteristics and R(i) were estimated using a multivariable, log-linear mixed model with inverse variance weighting. We found that cases with vomiting infected 1.28 (95 % CI: 1.11, 1.48) times the number of secondary cases compared to cases without vomiting, and LTCF residents infected 1.31 (95 % CI: 1.15, 1.50) times the number of secondary cases compared to staff. There was no difference in infectiousness between cases with and without diarrhea (1.07; 95 % CI: 0.90, 1.29). This suggests that vomiting, particularly by LTCF residents, was a primary driver of norovirus transmission. These results support control measures that limit exposure to vomitus during norovirus outbreaks in LTCFs.

OBJECTIVES: Acute gastroenteritis (AGE) outbreaks commonly occur in congregate settings, including schools and childcare facilities. These outbreaks disrupt institutions, causing absences and temporary facility closures. This study analyzed the epidemiology of school and childcare AGE outbreaks in the United States. METHODS: We analyzed AGE outbreaks occurring in kindergarten to grade 12 schools and childcare facilities reported via the National Outbreak Reporting System in the United States from 2009 to 2019 and compared this information to 2020 data. Outbreak and case characteristics were compared using the Kruskal-Wallis rank sum test, 2 goodness-of-fit test, and Fisher exact test. RESULTS: From 2009 to 2019, there were 2623 school, 1972 childcare, and 38 school and childcare outbreaks. School outbreaks were larger (median, 29 cases) than childcare outbreaks (median, 10 cases). Childcare outbreaks were longer (median, 15 days) than school outbreaks (median, 9 days). Norovirus (2383 outbreaks; 110190 illnesses) and Shigella spp. (756 outbreaks; 9123 illnesses) were the most reported etiologies. Norovirus was the leading etiology in schools; norovirus and Shigella spp. were dominant etiologies in childcare centers. Most (85.7%) outbreaks were spread via person-to-person contact. In 2020, 123 outbreaks were reported, 85% in the first quarter. CONCLUSIONS: Schools and childcare centers are common AGE outbreak settings in the United States. Most outbreaks were caused by norovirus and Shigella spp. and spread via person-to-person transmission. Fewer outbreaks were reported in 2020 from the COVID-19 pandemic. Prevention and control efforts should focus on interrupting transmission, including environmental disinfection, proper handwashing, safe diapering, and exclusion of ill persons.

Norovirus is the leading cause of acute gastroenteritis in the United States (1). In April 2020, the incidence of norovirus outbreaks in the United States declined substantially, likely because of implementation of COVID-19–related nonpharmaceutical interventions, such as facility closures, social distancing, and increased hand hygiene (2). Similar declines were observed in other countries (3,4). Norovirus outbreaks in the United States increased rapidly starting in January 2022, approaching prepandemic (i.e., 2012–2019) levels. Norovirus transmission can be prevented by thorough handwashing and proper cleaning and disinfection of contaminated surfaces © 2022, MMWR Recommendations and Reports.All Rights Reserved.

IMPORTANCE: Understanding risk factors for hospitalization in vaccinated persons and the association of COVID-19 vaccines with hospitalization rates is critical for public health efforts to control COVID-19. OBJECTIVE: To determine characteristics of COVID-19-associated hospitalizations among vaccinated persons and comparative hospitalization rates in unvaccinated and vaccinated persons. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2021, to April 30, 2022, patients 18 years or older with laboratory-confirmed SARS-CoV-2 infection were identified from more than 250 hospitals in the population-based COVID-19-Associated Hospitalization Surveillance Network. State immunization information system data were linked to cases, and the vaccination coverage data of the defined catchment population were used to compare hospitalization rates in unvaccinated and vaccinated individuals. Vaccinated and unvaccinated patient characteristics were compared in a representative sample with detailed medical record review; unweighted case counts and weighted percentages were calculated. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test result within 14 days before or during hospitalization. MAIN OUTCOMES AND MEASURES: COVID-19-associated hospitalization rates among vaccinated vs unvaccinated persons and factors associated with COVID-19-associated hospitalization in vaccinated persons were assessed. RESULTS: Using representative data from 19509 hospitalizations (see Table 1 for demographic information), monthly COVID-19-associated hospitalization rates ranged from 3.5 times to 17.7 times higher in unvaccinated persons than vaccinated persons regardless of booster dose status. From January to April 2022, when the Omicron variant was predominant, hospitalization rates were 10.5 times higher in unvaccinated persons and 2.5 times higher in vaccinated persons with no booster dose, respectively, compared with those who had received a booster dose. Among sampled cases, vaccinated hospitalized patients with COVID-19 were older than those who were unvaccinated (median [IQR] age, 70 [58-80] years vs 58 [46-70] years, respectively; P<.001) and more likely to have 3 or more underlying medical conditions (1926 [77.8%] vs 4124 [51.6%], respectively; P<.001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults hospitalized with COVID-19, unvaccinated adults were more likely to be hospitalized compared with vaccinated adults; hospitalization rates were lowest in those who had received a booster dose. Hospitalized vaccinated persons were older and more likely to have 3 or more underlying medical conditions and be long-term care facility residents compared with hospitalized unvaccinated persons. The study results suggest that clinicians and public health practitioners should continue to promote vaccination with all recommended doses for eligible persons.

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.

BACKGROUND: Globally, noroviruses cause infections year-round but have recognized winter seasonality in the northern hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact. METHODS: We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred from August 2009-July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions. RESULTS: During August 2009-July 2019, 24,995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, median norovirus season duration was 24 weeks, with onset occurring between October-December and offset occurring between April-May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions. CONCLUSIONS: Timing and duration of the US norovirus season varied annually, but generally occurred during October-May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors promoting virus transmission and help guide future interventions.

On April 21, 2022, CDC issued a health advisory(†) encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.(§) A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.(¶) Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases(†) of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.

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.

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.

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

BACKGROUND: In the US, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). METHODS: CDC collects epidemiologic and laboratory data on norovirus outbreaks from U.S. health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009-2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. RESULTS: During 2009-2018, 50 states, Washington D.C., and Puerto Rico reported 13,092 norovirus outbreaks and 416,284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009-2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (IQR: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%) and 75% occurred during December-March. Genogroup was reported for 7,292 outbreaks with 862 (11.8%) positive for GI and 6,370 (87.3%) for GII. Among 4,425 GII outbreaks with typing data, 3,618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% versus 10.9%; p<0.001). For every 1,000 cases, there were 21.6 hospitalizations and 2.3 deaths. CONCLUSIONS: LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains.

BACKGROUND: The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. The aim of this study is to describe 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 they were 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 1,932 in 2009 to 3,889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n=23,812, 62%) and contaminated food (n=9,234, 24%). Norovirus was the most commonly reported etiology, reported in 22,820 (59%) outbreaks, followed by Salmonella (n=2,449, 6%) and Shigella (n=1,171, 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<0.0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and E. coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). The 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.

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,(†) COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.(§) Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)(¶) data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,(††) and quarantining as recommended after exposure to persons with COVID-19.(§§).

Acute gastroenteritis (AGE), characterized by diarrhea and vomiting, is an important cause of global mortality, accounting for 9% of all deaths in children under five years of age. Since the reduction of rotavirus in countries that have included rotavirus vaccines in their national immunization programs, other viruses such as norovirus and sapovirus have emerged as more common causes of AGE. Due to widespread use of real-time RT-PCR testing, sapovirus has been increasingly reported as the etiologic agent in both AGE outbreaks and sporadic AGE cases. We aimed to assess the role of sapovirus as a cause of endemic AGE worldwide by conducting a systematic review of published studies that used molecular diagnostics to assess the prevalence of sapovirus among individuals with AGE symptoms. Of 106 articles included, the pooled sapovirus prevalence was 3.4%, with highest prevalence among children <5 years of age (4.4%) and among individuals in community settings (7.1%). Compared to studies that used conventional RT-PCR, RT-qPCR assays had a higher pooled prevalence (5.6%). Among individuals without AGE symptoms, the pooled sapovirus prevalence was 2.7%. These results highlight the relative contribution of sapovirus to cases of AGE, especially in community settings and among children <5 years of age.

In April 2020, the incidence of norovirus outbreaks reported to the National Outbreak Reporting System (NORS) dramatically declined. We used regression models to determine if this decline was best explained by underreporting, seasonal trends, or reduced exposure due to non-pharmaceutical interventions (NPIs) implemented for SARS-CoV-2 using data from 9 states from July 2012-July 2020. The decline in norovirus outbreaks was significant for all 9 states and underreporting or seasonality are unlikely to be the primary explanations for these findings. These patterns were similar across a variety of settings. NPIs appear to have reduced incidence of norovirus, a non-respiratory pathogen.

During 2009-2018, four adenovirus, 10 astrovirus, 123 rotavirus, and 107 sapovirus gastroenteritis outbreaks were reported to the US National Outbreak Reporting System (annual median 30 outbreaks). Most were attributable to person-to-person transmission in long-term care facilities, daycares, and schools. Investigations of norovirus-negative gastroenteritis outbreaks should include testing for these viruses.

Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.

Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.

BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well-characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston and Los Angeles), collectively serving >320,000 patients annually. METHODS: From July 1, 2016-June 30, 2018, we actively identified AGE inpatient cases and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatient cases through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens via multiplex gastrointestinal PCR panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatient cases, 394 controls, and 506 outpatient cases. Clostridioides difficile and norovirus were most frequently detected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<0.01 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%). Incidence per 100,000 population was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >/=65 years old (AGE: 459; C. difficile: 91; norovirus: 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/EIEC cases. Overall, 12% of AGE inpatient cases had ICU stays and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US Veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

Norovirus is the leading cause of foodborne illness outbreaks in the United States, and restaurants are the most common setting of foodborne norovirus outbreaks. Therefore, prevention and control of restaurant-related foodborne norovirus outbreaks is critical to lowering the burden of foodborne illness in the United States. Data for 124 norovirus outbreaks and outbreak restaurants were obtained from Centers for Disease Control and Prevention (CDC) surveillance systems and analyzed to identify relationships between restaurant characteristics and outbreak size and duration. Findings showed that restaurant characteristics, policies, and practices were linked with both outbreak size and duration. Compared to their counterparts, restaurants that had smaller outbreaks had the following characteristics: managers received food safety certification; managers and workers received food safety training; food workers wore gloves; and restaurants had cleaning policies. In addition, restaurants that provided food safety training to managers, served food items requiring less complex food preparation, and had fewer managers had shorter outbreaks compared to their counterparts. These findings suggest that restaurant characteristics play a role in norovirus outbreak prevention and intervention; therefore, implementing food safety training, policies, and practices likely reduces norovirus transmission, leading to smaller or shorter outbreaks.

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged </=18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. RESULTS: At 5 sites combined, 26 AFM cases were identified from 2005-2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September-October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005-July 2014 (n = 29), cases from August-December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013). CONCLUSION: Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases.

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis. Genogroup 2 type 4 (GII.4) has been the dominant norovirus genotype worldwide since its emergence in the mid-1990s. Individuals with a functional fucosyltransferase-2 gene, known as secretors, have increased susceptibility to GII.4 noroviruses. We hypothesized that this individual-level trait may drive GII.4 norovirus predominance at the human population level. METHODS: We conducted a systematic review for studies reporting norovirus outbreak or sporadic case genotypes and merged this with data on proportions of human secretor status in various countries from a separate systematic review. We used inverse variance-weighted linear regression to estimate magnitude of the population secretor-GII.4 proportion association. RESULTS: 219 genotype and 112 secretor studies with data from 38 countries were included in the analysis. Study-level GII.4 proportion among all noroviruses ranged from 0% to 100%. Country secretor proportion ranged from 43.8% to 93.9%. We observed a 0.69% (95% CI: 0.19, 1.18) increase in GII.4 proportion for each percent increase in human secretor proportion, controlling for Human Development Index. CONCLUSIONS: Norovirus evolution and diversity may be driven by local population human host genetics. Our results may have vaccine development implications including whether specific antigenic formulations would be required for different populations.