Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. 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.

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

COVID-19 vaccines are a critical tool for controlling the ongoing global pandemic. The Food and Drug Administration (FDA) has issued Emergency Use Authorizations for three COVID-19 vaccines for use in the United States.* In large, randomized-controlled trials, each vaccine was found to be safe and efficacious in preventing symptomatic, laboratory-confirmed COVID-19 (1-3). Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons (i.e. received all recommended doses of an FDA-authorized COVID-19 vaccine) will develop symptomatic or asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19 (2-8).

OBJECTIVES: Nonpharmaceutical interventions against coronavirus disease 2019 likely have a role in decreasing viral acute respiratory illnesses (ARIs). We aimed to assess the frequency of respiratory syncytial virus (RSV) and influenza ARIs before and during the coronavirus disease 2019 pandemic. METHODS: This study was a prospective, multicenter, population-based ARI surveillance, including children seen in the emergency departments and inpatient settings in 7 US cities for ARI. Respiratory samples were collected and evaluated by molecular testing. Generalized linear mixed-effects models were used to evaluate the association between community mitigation and number of eligible and proportion of RSV and influenza cases. RESULTS: Overall, 45 759 children were eligible; 25 415 were enrolled and tested; 25% and 14% were RSV-positive and influenza-positive, respectively. In 2020, we noted a decrease in eligible and enrolled ARI subjects after community mitigation measures were introduced, with no RSV or influenza detection from April 5, 2020, to April 30, 2020. Compared with 2016-2019, there was an average of 10.6 fewer eligible ARI cases per week per site and 63.9% and 45.8% lower odds of patients testing positive for RSV and influenza, respectively, during the 2020 community mitigation period. In all sites except Seattle, the proportions of positive tests for RSV and influenza in the 2020 community mitigation period were lower than predicted. CONCLUSIONS: Between March and April 2020, rapid declines in ARI cases and the proportions of RSV and influenza in children were consistently noted across 7 US cities, which could be attributable to community mitigation measures against severe acute respiratory syndrome coronavirus 2.

SARS-CoV-2, the virus that causes COVID-19, can spread rapidly in prisons and can be introduced by staff members and newly transferred incarcerated persons (1,2). On September 28, 2020, the Wisconsin Department of Health Services (DHS) contacted CDC to report a COVID-19 outbreak in a state prison (prison A). During October 6-20, a CDC team investigated the outbreak, which began with 12 cases detected from specimens collected during August 17-24 from incarcerated persons housed within the same unit, 10 of whom were transferred together on August 13 and under quarantine following prison intake procedures (intake quarantine). Potentially exposed persons within the unit began a 14-day group quarantine on August 25. However, quarantine was not restarted after quarantined persons were potentially exposed to incarcerated persons with COVID-19 who were moved to the unit. During the subsequent 8 weeks (August 14-October 22), 869 (79.4%) of 1,095 incarcerated persons and 69 (22.6%) of 305 staff members at prison A received positive test results for SARS-CoV-2. Whole genome sequencing (WGS) of specimens from 172 cases among incarcerated persons showed that all clustered in the same lineage; this finding, along with others, demonstrated that facility spread originated with the transferred cohort. To effectively implement a cohorted quarantine, which is a harm reduction strategy for correctional settings with limited space, CDC's interim guidance recommendation is to serial test cohorts, restarting the 14-day quarantine period when a new case is identified (3). Implementing more effective intake quarantine procedures and available mitigation measures, including vaccination, among incarcerated persons is important to controlling transmission in prisons. Understanding and addressing the challenges faced by correctional facilities to implement medical isolation and quarantine can help reduce and prevent outbreaks.

BACKGROUND: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. OBJECTIVE: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. METHODS: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. RESULTS: Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. CONCLUSIONS: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22222.

BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the US. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, is needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among Veterans in a multi-site surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers (VAMCs: Atlanta, Bronx, Houston, Palo Alto, and Los Angeles), collectively serving >396,000 patients annually. From February 27- July 17 2020, we actively identified SARS-CoV-2 positive inpatient cases through screening of admitted patients and review of laboratory test results. We manually abstracted medical charts for demographics, underlying medical conditions, and clinical outcomes of COVID-19 hospitalized patients. We calculated hospitalization incidence and incidence rate ratios, and relative risk (RR) for invasive mechanical ventilation, intensive care unit (ICU) admission, and death after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed hospitalized COVID-19 cases. Median age was 70 years, 66% were aged ≥65 years, and 94% were male. Most COVID-19 diagnoses were among non-Hispanic Blacks (52%), followed by non-Hispanic Whites (25%) and Hispanic or Latinos (18%). Hospitalization rates were highest among Veterans aged ≥85 years, Hispanic or Latino, and non-Hispanic Black (430, 317 and 298 per 100,000, respectively); Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with Veterans aged 18-29 years (95% CI: 5.7-34.6), while Hispanic or Latino and Black Veterans had a 4.6 and 4.2-fold increased rate of hospitalization compared with non-Hispanic White Veterans (95% CI: 3.6-5.9), respectively. Overall, 11.6% of patients required invasive mechanical ventilation, 26.6% were admitted to the intensive care unit (ICU), and 16.9% died in hospital. The adjusted RR for invasive mechanical ventilation and ICU admission did not differ by age group or race/ethnicity, but Veterans aged ≥65 had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged <65 years (95% CI: 2.4-8.6). CONCLUSIONS: COVID-19 surveillance at 5 VAMCs across the US demonstrated higher hospitalization rates and severe outcomes in older Veterans, and higher hospitalization rates in Hispanic or Latino and non-Hispanic Black Veterans compared to non-Hispanic White Veterans. These data highlight the need for targeted prevention and timely treatment for Veterans, with special attention to increasing age, Hispanic or Latino and non-Hispanic Black Veterans.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, although increasing evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems (1). Data that examine all in-hospital complications of COVID-19 and that compare these complications with those associated with other viral respiratory pathogens, such as influenza, are lacking. To assess complications of COVID-19 and influenza, electronic health records (EHRs) from 3,948 hospitalized patients with COVID-19 (March 1-May 31, 2020) and 5,453 hospitalized patients with influenza (October 1, 2018-February 1, 2020) from the national Veterans Health Administration (VHA), the largest integrated health care system in the United States,* were analyzed. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, complications in patients with laboratory-confirmed COVID-19 were compared with those in patients with influenza. Risk ratios were calculated and adjusted for age, sex, race/ethnicity, and underlying medical conditions; proportions of complications were stratified among patients with COVID-19 by race/ethnicity. Patients with COVID-19 had almost 19 times the risk for acute respiratory distress syndrome (ARDS) than did patients with influenza, (adjusted risk ratio [aRR] = 18.60; 95% confidence interval [CI] = 12.40-28.00), and more than twice the risk for myocarditis (2.56; 1.17-5.59), deep vein thrombosis (2.81; 2.04-3.87), pulmonary embolism (2.10; 1.53-2.89), intracranial hemorrhage (2.85; 1.35-6.03), acute hepatitis/liver failure (3.13; 1.92-5.10), bacteremia (2.46; 1.91-3.18), and pressure ulcers (2.65; 2.14-3.27). The risks for exacerbations of asthma (0.27; 0.16-0.44) and chronic obstructive pulmonary disease (COPD) (0.37; 0.32-0.42) were lower among patients with COVID-19 than among those with influenza. The percentage of COVID-19 patients who died while hospitalized (21.0%) was more than five times that of influenza patients (3.8%), and the duration of hospitalization was almost three times longer for COVID-19 patients. Among patients with COVID-19, the risk for respiratory, neurologic, and renal complications, and sepsis was higher among non-Hispanic Black or African American (Black) patients, patients of other races, and Hispanic or Latino (Hispanic) patients compared with those in non-Hispanic White (White) patients, even after adjusting for age and underlying medical conditions. These findings highlight the higher risk for most complications associated with COVID-19 compared with influenza and might aid clinicians and researchers in recognizing, monitoring, and managing the spectrum of COVID-19 manifestations. The higher risk for certain complications among racial and ethnic minority patients provides further evidence that certain racial and ethnic minority groups are disproportionally affected by COVID-19 and that this disparity is not solely accounted for by age and underlying medical conditions.

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: Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19. METHODS: We analyzed data from 2,491 adults hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020 identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network comprising 154 acute care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality. RESULTS: Ninety-two percent of patients had >/=1 underlying condition; 32% required ICU admission; 19% invasive mechanical ventilation; and 17% died. 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). CONCLUSION: In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.

Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January-March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged >/=50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged >/=65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)(dagger) to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.

On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.

BACKGROUND: Outbreaks of respiratory syncytial virus (RSV) in neonatal intensive care units (NICUs) are of concern because of the risk of severe disease in young infants. We describe an outbreak of RSV in a NICU and use whole genome sequencing (WGS) to better understand the relatedness of viruses among patients.SummaryUsing whole genome sequencing, we found 2 introductions of respiratory syncytial virus (RSV) into a neonatal intensive care unit causing 7 infections. This outbreak highlights the risk of healthcare-associated infections during RSV season; early recognition is critical to limit transmission. METHODS: An investigation was conducted to identify patients and describe their clinical course. Infection control measures were implemented to prevent further spread. Respiratory specimens from outbreak-related patients and the community were tested using WGS. Phylogenetic trees were constructed to understand relatedness of the viruses. RESULTS: Seven patients developed respiratory symptoms within an 11-day span in December 2017 and were diagnosed with RSV; 6 patients (86%) were preterm and 1 had chronic lung disease. Three patients required additional respiratory support after symptom onset, and none died. Six of 7 patients were part of the same cluster based on > 99.99% nucleotide agreement with each other and 3 unique single-nucleotide polymorphisms were identified in viruses sequenced from those patients. The seventh patient was admitted from the community with respiratory symptoms and had a genetically distinct virus that was not related to the other 6. Implementation of enhanced infection control measures likely limited the spread. CONCLUSIONS: Using WGS, we found 2 distinct introductions of RSV into a NICU, highlighting the risk of healthcare-associated infections during RSV season. Early recognition and infection control measures likely limited spread, emphasizing the importance of considering RSV in the differential diagnosis of respiratory infections in healthcare settings.

BACKGROUND: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. METHODS: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. RESULTS: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. CONCLUSIONS: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

BACKGROUND: The objectives of the current study were to assess changes in colorectal cancer (CRC) screening uptake and the cost-effectiveness of implementing multiple evidence-based interventions (EBIs). EBIs were implemented at 2 federally qualified health centers that participated in the Colorado Department of Public Health and Environment's Clinic Quality Improvement for Population Health initiative. METHODS: Interventions included patient and provider reminder systems (health system 1), provider assessment and feedback (health systems 1 and 2), and numerous support activities (health systems 1 and 2). The authors evaluated health system 1 from July 2013 to June 2015 and health system 2 from July 2014 to June 2017. Evaluation measures included annual CRC screening uptake, EBIs implemented, funds received and expended by each health system to implement EBIs, and intervention costs to the Colorado Department of Public Health and Environment and health systems. RESULTS: CRC screening uptake increased by 18 percentage points in health system 1 and 10 percentage points in health system 2. The improvements in CRC screening uptake, not including the cost of the screening tests, were obtained at an added cost ranging from $24 to $29 per person screened. CONCLUSIONS: In both health systems, the multicomponent interventions implemented likely resulted in improvements in CRC screening. The results suggest that significant increases in CRC screening uptake can be achieved in federally qualified health centers when appropriate technical support and health system commitment are present. The cost estimates of the multicomponent interventions suggest that these interventions and support activities can be implemented in a cost-effective manner.

Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

OBJECTIVE: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. DESIGN: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). METHODS: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. RESULTS: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). CONCLUSION: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.

Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3-5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.

The Centers for Disease Control and Prevention Emerging Infections Program (EIP) network conducts population-based surveillance for pathogens of public health importance. Central to obtaining estimates of disease burden and tracking microbiological characteristics of these infections is accurate laboratory detection of pathogens. The use of culture-independent diagnostic tests (CIDTs) in clinical settings presents both opportunities and challenges to EIP surveillance. Because CIDTs offer better sensitivity than culture and are relatively easy to perform, their use could potentially improve estimates of disease burden. However, changes in clinical testing practices, use of tests with different sensitivities and specificities, and changes to case definitions make it challenging to monitor trends. Isolates are still needed for performing strain typing, antimicrobial resistance testing, and identifying other molecular characteristics of organisms. In this article, we outline current and future EIP activities to address issues associated with adoption of CIDTs, which may apply to other public health surveillance.