We investigated a suspected norovirus outbreak associated with a wedding reception in Wisconsin in May 2015. Fifty-six of 106 (53%) wedding attendees were interviewed and 23 (41%) reported symptoms consistent with norovirus infection. A retrospective cohort study identified fruit salad as the likely vehicle of infection (risk ratio 3.2, 95% confidence interval 1.1- 8.3). Norovirus was detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) in stool specimens collected from four attendees and one food handler and in 12 leftover fruit salad samples from both an opened and a sealed container. Norovirus-positive clinical samples (n=4) were genotyped as GII.4 Sydney and norovirus-positive fruit salad samples (n=2) confirmed the presence of GII.4 norovirus by Sanger sequencing with 98% nucleotide (n=236) similarity in 5' end of ORF2 between fruit salad and clinical specimens. In conclusion, this comprehensive norovirus outbreak investigation combined epidemiologic, virologic, and environmental findings to traceback the contaminated food as the source of the outbreak.

CDC continues to track the evolution of SARS-CoV-2, including the Omicron variant and its descendants, using national genomic surveillance. This report summarizes U.S. trends in variant proportion estimates during May 2023-September 2024, a period when SARS-CoV-2 lineages primarily comprised descendants of Omicron variants XBB and JN.1. During summer and fall 2023, multiple descendants of XBB with immune escape substitutions emerged and reached >10% prevalence, including EG.5-like lineages by June 24, FL.1.5.1-like lineages by August 5, HV.1 lineage by September 30, and HK.3-like lineages by November 11. In winter 2023, the JN.1 variant emerged in the United States and rapidly attained predominance nationwide, representing a substantial genetic shift (>30 spike protein amino acid differences) from XBB lineages. Descendants of JN.1 subsequently circulated and reached >10% prevalence, including KQ.1-like and KP.2-like lineages by April 13, KP.3 and LB.1-like lineages by May 25, and KP.3.1.1 by July 20. Surges in COVID-19 cases occurred in winter 2024 during the shift to JN.1 predominance, as well as in summer 2023 and 2024 during circulation of multiple XBB and JN.1 descendants, respectively. The ongoing evolution of the Omicron variant highlights the importance of continued genomic surveillance to guide medical countermeasure development, including the selection of antigens for updated COVID-19 vaccines.

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: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

We conducted a large surveillance study among members of an integrated healthcare delivery system in Pacific Northwest of the United States to estimate medical costs attributable to medically attended acute gastroenteritis (MAAGE) on the day care was sought and during 30-day follow-up. We used multivariable regression to compare costs of MAAGE and non-MAAGE cases matched on age, gender, and index time. Differences accounted for confounders, including race, ethnicity, and history of chronic underlying conditions. Analyses included 73,140 MAAGE episodes from adults and 18,617 from children who were Kaiser Permanente Northwest members during 2014-2016. Total costs were higher for MAAGE cases relative to non-MAAGE comparators as were costs on the day care was sought and costs during follow-up. Costs of MAAGE are substantial relative to the cost of usual-care medical services, and much of the burden accrues during short-term follow-up.

OBJECTIVE: Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. METHODS: From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. RESULTS: Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. CONCLUSIONS: Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

BACKGROUND: Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. METHODS: We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. RESULTS: In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). CONCLUSIONS: Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention. METHODS: We conducted prospective surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates. RESULTS: Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval [CI]: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 [95% CI: 22.5-25.2] per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 [95% CI: 1.76-2.11]). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio [aOR] = 1.97 [95% CI: 1.54-2.52] and aOR = 1.56 [95% CI: 1.18-2.06], respectively, compared with 24-59 months), prematurity (aOR = 1.32 [95% CI: 1.08-1.60]) and comorbid conditions (aOR = 1.35 [95% CI: 1.10-1.66]). CONCLUSIONS: Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.

BACKGROUND: SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse birth outcomes such as preterm birth, stillbirth, and maternal and infant complications. Previous research suggests an increased risk of severe COVID-19 illness and stillbirth in pregnant people during delta variant predominance in 2021; however, those studies did not assess timing of infection during pregnancy, and few of them described COVID-19 vaccination status. OBJECTIVE: Using a large population-based cohort, this study compared pregnancy and infant outcomes and described demographic and clinical characteristics of pregnant people with SARS-CoV-2 infection prior to and during the delta variant period. STUDY DESIGN: This retrospective cohort analysis included persons with confirmed SARS-CoV-2 infection in pregnancy from 6 US jurisdictions reporting to the Surveillance for Emerging Threats to Pregnant People and Infants Network. Data were collected through case reports of polymerase chain reaction-positive pregnant persons and linkages to birth certificates, fetal death records, and immunization records. We described clinical characteristics and compared frequency of spontaneous abortion (<20 weeks of gestation), stillbirth (≥20 weeks), preterm birth (<37 weeks), small for gestational age, and term infant neonatal intensive care unit admission between the time periods of pre-delta and delta variant predominance. Study time periods were determined by when variants constituted more than 50% of sequences isolated according to regional SARS-CoV-2 genomic surveillance data, with time periods defined for pre-delta (March 3, 2020-June 25, 2021) and Delta (June 26, 2021-December 25, 2021). Adjusted prevalence ratios were estimated for each outcome measure using Poisson regression and were adjusted for continuous maternal age, race and ethnicity, and insurance status at delivery. RESULTS: Among 57,563 pregnancy outcomes, 57,188 (99.3%) were liveborn infants, 65 (0.1%) were spontaneous abortions, and 310 (0.5%) were stillbirths. Most pregnant persons were unvaccinated at the time of SARS-CoV-2 infection, with a higher proportion in pre-delta (99.4%) than in the delta period (78.4%). Of those with infections during delta and who were previously vaccinated, the timing from last vaccination to infection was a median of 183 days. Compared to pre-delta, infections during delta were associated with a higher frequency of stillbirths (0.7% vs 0.4%; adjusted prevalence ratio, 1.55; 95% confidence interval, 1.14-2.09) and preterm births (12.8% vs 11.9%; adjusted prevalence ratio, 1.14; 95% confidence interval, 1.07-1.20). The delta period was associated with a lower frequency of neonatal intensive care unit admission (adjusted prevalence ratio, 0.74; 95% confidence interval, 0.67-0.82) than in the pre-delta period. During the delta period, infection during the third trimester was associated with a higher frequency of preterm birth (adjusted prevalence ratio, 1.41; 95% confidence interval, 1.28-1.56) and neonatal intensive care unit admission (adjusted prevalence ratio, 1.21; 95% confidence interval, 1.01-1.45) compared to the first and second trimester combined. CONCLUSION: In this US-based cohort of persons with SARS-CoV-2 infection in pregnancy, the majority were unvaccinated, and frequencies of stillbirth and preterm birth were higher during the delta variant predominance period than in the pre-delta period. During the delta period, frequency of preterm birth and neonatal intensive care unit admission was higher among infections occurring in the third trimester vs those earlier in pregnancy. These findings demonstrate population-level increases of adverse fetal and infant outcomes, specifically in the presence of a COVID-19 variant with more severe presentation.

Before 2023, there were no immunizing tools to protect older adults and all infants from illness and death due to respiratory syncytial virus (RSV). In 2023, two RSV vaccines for older adults, one of which is also approved for use in pregnant persons, and a long-acting monoclonal antibody to protect infants and some toddlers up to 19 months of age were approved by the Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.1-3 These major developments occurred nearly 60 years after a formalin-inactivated RSV vaccine that had been administered to children in clinical trials resulted in enhanced respiratory disease in seronegative children who had been vaccinated, and hopes for a safe and effective RSV vaccine were dashed, or at least postponed. Investigation into why this vaccine failed ultimately led to identification of the stabilized prefusion conformation of the fusion (F) glycoprotein target, which propelled the scientific community to subsequently make remarkable progress in the development of RSV vaccines.4 | | Furthermore, the discovery of the RSV prefusion F protein as a stable antigen was foundational to the work on vaccine development for coronaviruses before the Covid-19 pandemic, and researchers were able to quickly pivot to targeting SARS-CoV-2 spike protein when it emerged.5 In December 2020, the first mRNA vaccines against SARS-CoV-2 were authorized, 1 year after the disease and causative virus were first recognized. The development of these vaccines benefited from the head start provided by previous research on RSV vaccines and the mRNA platform that allows for fast production of large quantities of vaccine. Both factors were critical in controlling the Covid-19 pandemic, but they also show the immense potential for the rapid introduction of new vaccines worldwide.

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

Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats.

BACKGROUND: In the United States, public health surveillance systems often underestimate the burden of acute gastroenteritis (AGE) because they only identify disease among those who interact with the healthcare system. OBJECTIVE: To identify factors associated with healthcare-seeking behavior among individuals experiencing community-acquired AGE. METHODS: From October 2016 -September 2017, we conducted a weekly, age-stratified, random sample of Kaiser Permanente Northwest members located in northwest Oregon and southwest Washington, United States. Individuals who completed the online survey and experienced AGE were included in the analysis. Univariate and multivariable logistic regressions were performed to identify predictors of healthcare-seeking behavior. RESULTS: Of the 3,894 survey respondents, 395 experienced an AGE episode and were eligible for analysis, of whom, 82 (21%) sought care for their AGE episode. In the final multivariable model, individuals with a concurrent fever (odds ratio [OR]: 4.76, 95% confidence interval [95% CI]: 2.48-9.13), increased diarrhea duration (≥6 days vs 1-4 days, OR: 4.22, 95% CI: 1.78-10.03), or increased vomiting duration (≥3 days vs 1 days, OR: 2.97, 95% CI: 1.22-7.26), were significantly more likely to seek healthcare. In the adjusted model, no sociodemographic or chronic disease variables were associated with healthcare-seeking behavior. CONCLUSION: These findings suggest that individuals with a short duration of AGE and those without concurrent fever are underrepresented in healthcare facility-based surveillance systems.

BACKGROUND: Norovirus is a major cause of endemic acute gastroenteritis (AGE) worldwide. We described the epidemiology, risk factors, and genotypic distribution of noroviruses among hospitalized patients of all ages in Bangladesh. METHODS: From March 2018 to October 2021, 1250 AGE case patients and controls (age, sex, season, and site matched) were enrolled at 10 hospitals. Demographic and clinical information was collected; real-time reverse-transcriptase polymerase chain reaction (RT-PCR) used to test stool specimens, and positive samples were genotyped. RESULTS: Norovirus was detected in 9% of cases (111 of 1250) and 15% (182 of 1250) of controls. Eighty-two percent of norovirus-positive cases were in children <5 years old. Norovirus-positive AGE hospitalizations occurred year-round, with peaks in April and October. Risk factors for norovirus included age <5 years (adjusted odds ratio, 3.1 [95% confidence interval, 1.9-5.2]) and exposure to a patient with AGE in the 10 days before enrollment (3.8 [1.9-7.2]). GII.3[P16] and GII.4 Sydney[P16] were the predominant genotypes. CONCLUSIONS: We highlight the burden of norovirus in hospital settings. Young age and recent exposure to a patient with AGE were risk factors for norovirus. A high prevalence of norovirus among controls might represent asymptomatic reinfections or prolonged shedding from a previous infection; carefully designed longitudinal studies are needed to improve our understanding of norovirus infections in Bangladesh.

Background Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection.Methods Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020–January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics.Results Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30–39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions.Conclusions Pregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.Summary Among pregnant women with COVID-19, older age and underlying medical conditions were risk factors for increased illness severity. These findings can be used to inform pregnant women about their risk for severe COVID-19 illness and public health messaging.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThis activity was reviewed by CDC, determined to be a non-research, public health surveillance activity, and was conducted consistent with applicable federal law and CDC policy.Clinical Protocols https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643898/ Funding StatementThis study was performed as regular work of the Centers for Disease Control and Prevention. This work is supported by the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Cooperative Agreement (ELC CK19-1904) and through contractual mechanisms, including the Local Health Department Initiative.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 the human subjects advisor of the U.S. Centers for Disease Control and Prevention (CDC), National Center on Birth Defects and Developmental Disorders and was determined to be non-research, public health surveillance and exempt from IRB review. This activity was conducted consistent with applicable federal law and CDC policy. (Department of Health and Human Services - 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq. Available from: https://www.hhs.gov/ohrp/sites/default/files/ohrp/policy/ohrpregulations.pdf.)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, p ease 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.YesThese data are collected under relevant provisions of the Public Health Service Act and are protected at CDC by an Assurance of Confidentiality (Section 308(d) of the Public Health Service Act, 42 U.S.C. section 242 m(d)) (https://www.cdc.gov/od/science/integrity/confidentiality/), which prohibits use or disclosure of any identifiable or potentially identifiable information collected under the Assurance for purposes other than those set out in the Assurance. Publicly available aggregated data are available: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/birth-data-on-covid-19.html. Requests for access will be considered on a case by case basis, and inquiries should be directed to setnet@cdc.gov

Background Identification of risk factors for COVID-19-associated hospitalization is needed to guide prevention and clinical care.Objective To examine if age, sex, race/ethnicity, and underlying medical conditions is independently associated with COVID-19-associated hospitalizations.Design Cross-sectional.Setting 70 counties within 12 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) and a population-based sample of non-hospitalized adults residing in the COVID-NET catchment area from the Behavioral Risk Factor Surveillance System.Participants U.S. community-dwelling adults (≥18 years) with laboratory-confirmed COVID-19-associated hospitalizations, March 1- June 23, 2020.Measurements Adjusted rate ratios (aRR) of hospitalization by age, sex, race/ethnicity and underlying medical conditions (hypertension, coronary artery disease, history of stroke, diabetes, obesity [BMI ≥30 kg/m2], severe obesity [BMI≥40 kg/m2], chronic kidney disease, asthma, and chronic obstructive pulmonary disease).Results Our sample included 5,416 adults with COVID-19-associated hospitalizations. Adults with (versus without) severe obesity (aRR:4.4; 95%CI: 3.4, 5.7), chronic kidney disease (aRR:4.0; 95%CI: 3.0, 5.2), diabetes (aRR:3.2; 95%CI: 2.5, 4.1), obesity (aRR:2.9; 95%CI: 2.3, 3.5), hypertension (aRR:2.8; 95%CI: 2.3, 3.4), and asthma (aRR:1.4; 95%CI: 1.1, 1.7) had higher rates of hospitalization, after adjusting for age, sex, and race/ethnicity. In models adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults ≥65 years, 45-64 years (versus 18-44 years), males (versus females), and non-Hispanic black and other race/ethnicities (versus non-Hispanic whites).Limitations Interim analysis limited to hospitalizations with underlying medical condition data.Conclusion Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.Competing Interest StatementDr. Anderson reports personal fees from AbbVie, personal fees from Pfizer, grants from Pfizer, grants from Merck, grants from Micron, grants from Paxvax, grants from Sanofi Pasteur, grants from Novavax, grants from MedImmune, grants from Regeneron, grants from GSK, outside the submitted work. Mr. Henderson, Ms. Kim, Ms. George, and Ms. Hill report grants from Council of State and Territorial Epidemiologists (CSTE), during the conduct of the study. Dr. Lynfield reports grants from CDC- Emerging Infections Program, during the conduct of the study; and Royalties from a book on infectious disease surveillance and compensation for AAP Red Book (Report from Committee on Infectious Disease) donated to Minnesota Dept of Health. Dr. Schaffner reports grants from CDC, during the conduct of the study; personal fees from VBI Vaccines, outside the submitted work. Dr. Talbot reports other from Seqirus, outside the submitted work.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 analysis was exempt from CDC's Institutional Review Board, as it was considered part of public health surveillance and emergency response. Participating sites obtained approval for the COVID-NET surveillance protocol from their respective state and local IRBs, as required.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 regi try, 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.YesData is not publically available at this time.

Importance Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States.Design Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies.Setting Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State’s (WA) Puget Sound region.Participants Persons of all ages with serum collected during intervals from March 23 through May 3, 2020.Exposure SARS-CoV-2 virus infection.Main outcomes and measures We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date.Results We tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site.Conclusions and relevance Our seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, &gt;10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures.Question What proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020?Findings We tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data.Meaning For most sites, evidence suggests &gt;10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the Centers for Disease Control and Prevention.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 protocol underwent review by CDC human subjects research officials, who determined that the testing represented non-research activity in the setting of a public health response to the COVID-19 pandemic.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 su h 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.YesA limited dataset will be made publicly available at a later time.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll 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.YesData may be available upon reasonable request.

Background As of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally.Objective To describe risk factors for severe outcomes among adults hospitalized with COVID-19.Design Cohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network.Setting 154 acute care hospitals in 74 counties in 13 states.Patients 2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020.Measurements Age, sex, race/ethnicity, and underlying medical conditions.Results Ninety-two percent of patients had ≥1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and ≥85 years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death.Limitation Data were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded.Conclusion In-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies.Funding Source This work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Competing Interest StatementH. Keipp Talbot reports personal fees from Seqirus outside the submitted work. William Schaffner reports personal fees from Pfizer and personal fees from Roche Diagnostics outside the submitted work. Evan Anderson reports personal fees from Abbvie and Pfizer outside the submitted work. H. Keipp Talbot reports grants from Sanofi outside the submitted work; Mary Hill reports grants from CSTE, during the conduct of the study; Melissa Sutton reports grants from CDC Emerging Infections Program during the conduct of the study; William Schaffner reports grants from CDC during the conduct of the study. Sue Kim reports grants from CSTE during the conduct of the study. Evan Anderson reports grants from Pfizer, grants from MedImmune, grants from Regeneron, grants from PaxVax, grants from Merck, grants from Novavax, grants from Sanofi-Pasteur, grants from Micron, outside the submitted work. Laurie Billing reports grants from the Council of State and Territorial Epidemiologists (CSTE) and the Centers for Disease Control and Prevention (CDC) during the conduct of the study.Funding StatementThis work was supported by grant CK17-1701 from the Centers of Disease Control and Prevention through an Emerging Infections Program cooperative agreement and by Cooperative Agreement Number NU38OT000297-02-00 awarded to the Council of State and Territorial Epidemiologists from the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that al 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.YesAggregate data is available on CDC’s COVID-NET Interactive website. https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html

Background Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms.Methods We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted ‘immunity’), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data.Results Recreating the low attack rates observed in daycare and school outbreaks required a model with immunity. However, immunity alone resulted in shorter duration outbreaks than what was observed. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data.Conclusions The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. Interventions should leverage population immunity and encourage more rigorous individual exclusion to improve venue-level control measures.Competing Interest StatementDr. Lopman reports personal fees from Takeda Pharmaceuticals, CDC Foundation, and Hall Booth Smith, P.C. outside the submitted work.Funding StatementThis Study was funded by the Joint Initiative for Vaccine Economics, Phase 5, a cooperative agreement between the University of Michigan and the Centers for Disease Control and Prevention (U01IP000965). Additionally, this study was funded by the National Institute of General Medical Sciences (U01GM110712). Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll 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.YesThe surveillance datasets are available from the Centers for Disease Control and Prevention upon request and application. Computing code available from the corresponding author upon reasonable request.

The role of individual case characteristics, such as symptoms or demographics, in norovirus transmissibility is poorly understood. Six nursing home norovirus outbreaks occurring in South Carolina, U.S. from 2014 to 2016 were examined. We aimed to quantify the contribution of symptoms and other case characteristics in norovirus transmission using the reproduction number (REi) as an estimate of individual case infectivity and to examine how transmission changes over the course of an outbreak. Individual estimates of REi were calculated using a maximum likelihood procedure to infer the average number of secondary cases generated by each case. The associations between case characteristics and REi were estimated using a multivariate mixed linear model. Outbreaks began with one to three index case(s) with large estimated REi’s (range: 1.48 to 8.70) relative to subsequent cases. Of the 209 cases, 155 (75%) vomited, 164 (79%) had diarrhea, and 158 (76%) were nursing home residents (vs. staff). Cases who vomited infected 2.74 (95% CI: 1.90, 3.94) more individuals than non-vomiters, cases with diarrhea infected 1.62 (95% CI: 1.09, 2.41) more individuals than cases without diarrhea, and resident-cases infected 1.69 (95% CI: 1.18, 2.42) more individuals than staff-cases. Index cases tended to be residents (vs. staff) who vomited and infected considerably more secondary cases compared to non-index cases. Results suggest that individuals, particularly residents, who vomit are more infectious and tend to drive norovirus transmission in U.S. nursing home norovirus outbreaks. While diarrhea also plays a role in norovirus transmission, it is to a lesser degree than vomiting in these settings. Results lend support for prevention and control measures that focus on cases who vomit, particularly if those cases are residents.Author summary The majority of all norovirus outbreaks reported to the CDC occur in long-term care facilities (LTCFs), including nursing homes, where older residents are at risk for more severe or prolonged infection. Because there is currently no publicly available norovirus vaccine, sound control measures are key to controlling norovirus outbreaks, but there is little evidence that standard control measures are effective in reducing the size and/or duration of LTCF norovirus outbreaks. Hence, studies leading to a better understanding of disease spread and prevention of additional cases, and thus more effective control measures, are needed. To this end, we aimed to quantify factors associated with norovirus transmission and to examine how transmission changes over the course of an outbreak. We show that vomiting and, to a lesser extent, diarrhea are critical in initiating and sustaining norovirus transmission in U.S. nursing home norovirus outbreaks. We also show that nursing home residents, rather than staff, are the primary drivers of transmission. Results suggest that control measures focusing on cases who vomit, particularly if those cases are residents, would be most effective at curtailing norovirus transmission in these settings.

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHOD(S): INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULT(S): Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSION(S): This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

BACKGROUND: Understanding the drivers of SARS-CoV-2 transmission can inform the development of interventions. We evaluated transmission identified by contact tracing investigations between March-May 2020 in Salt Lake County, Utah, to quantify the impact of this intervention and identify risk factors for transmission. METHODS: RT-PCR positive and untested symptomatic contacts were classified as confirmed and probable secondary case-patients, respectively. We compared the number of case-patients and close contacts generated by different groups, and used logistic regression to evaluate factors associated with transmission. RESULTS: Data were collected on 184 index case-patients and up to six generations of contacts. Of 1,499 close contacts, 374 (25%) were classified as secondary case-patients. Decreased transmission odds were observed for contacts aged <18 years (OR = 0.55 [95% CI: 0.38-0.79]), versus 18-44 years, and for workplace (OR = 0.36 [95% CI: 0.23-0.55]) and social (OR = 0.44 [95% CI: 0.28-0.66]) contacts, versus household contacts. Higher transmission odds were observed for case-patient's spouses than other household contacts (OR = 2.25 [95% CI: 1.52-3.35]). Compared to index case-patients identified in the community, secondary case-patients identified through contract-tracing generated significantly fewer close contacts and secondary case-patients of their own. Transmission was heterogeneous, with 41% of index case-patients generating 81% of directly-linked secondary case-patients. CONCLUSIONS: Given sufficient resources and complementary public health measures, contact tracing can contain known chains of SARS-CoV-2 transmission. Transmission is associated with age and exposure setting, and can be highly variable, with a few infections generating a disproportionately high share of onward transmission.

CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).

CaliciNet China, a network of provincial, county, and city laboratories coordinated by the Chinese Centers for Disease Control and Prevention, was launched in October 2016 to monitor the epidemiology and genotype distribution of norovirus outbreaks in China. During October 2016-September 2018, a total of 556 norovirus outbreaks were reported, and positive fecal samples from 470 (84.5%) outbreaks were genotyped. Most of these outbreaks were associated with person-to-person transmission (95.1%), occurred in childcare centers or schools (78.2%), and were reported during November-March of each year (63.5%). During the 2-year study period, 81.2% of all norovirus outbreaks were typed as GII.2[P16]. In China, most norovirus outbreaks are reported by childcare centers or schools; GII.2[P16] is the predominant genotype. Ongoing surveillance by CaliciNet China will provide information about the evolving norovirus genotype distribution and outbreak characteristics important for the development of effective interventions, including vaccines.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced the transmission of some viral respiratory pathogens.1 In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020,2 and remained low during October 2020–May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1–4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.

PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic. Here, we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA-binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.