Intrinsic risk factors for alpha-gal syndrome in a case-control study, 2019 to 2020.

BACKGROUND: Alpha-gal syndrome (AGS) is an allergy to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in most mammals. Evidence indicates that AGS develops after a tick bite, and in the United States, AGS is most associated with bites from Amblyomma americanum (lone star tick); however, not all persons bitten by ticks develop clinical AGS. OBJECTIVE: To investigate intrinsic risk factors associated with the development of AGS. METHODS: We performed a case-control study among adults presenting for diagnosis or management of AGS at an allergy clinic in North Carolina during 2019 to 2020 and compared them with controls enrolled from 2 nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data, and blood was obtained for alpha-gal-specific IgE and other testing. RESULTS: The 82 enrolled case patients and 191 controls did not differ significantly by age or sex. Case patients were more likely than controls to have A or O blood types (non B-antigen), have experienced childhood allergies, and have a family history of AGS and other food allergies. Case patients were also more likely to report experiencing long healing times for insect bites or stings and a family history of allergy to stinging or biting insects. CONCLUSION: This study suggested that intrinsic factors contribute to risk of developing AGS. Some traits are genetic, but common behaviors among households and family units likely also contribute. Identification of these risk factors can inform personal risk, aid health care providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology.

Estimating the early impact of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older: an ecological analysis of national surveillance data.

BACKGROUND: In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older. METHODS: We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods. FINDINGS: The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI -14 to 69 among adults aged 65-74 years and by 30%, -47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear. INTERPRETATION: The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults. FUNDING: None.

Clinical and laboratory features of patients diagnosed with alpha-gal syndrome-2010-2019.

BACKGROUND: Alpha-gal syndrome (AGS) is an IgE-mediated allergy to galactose-alpha-1,3-galactose. Clinical presentation ranges from hives to anaphylaxis; episodes typically occur 2-6 h after exposure to alpha-gal-containing products. In the United States, lone star tick bites are associated with the development of AGS. To characterize features of AGS, we evaluated a cohort of patients presenting for care at the University of North Carolina, focusing on symptoms, severity, and identifying features unique to specific alpha-gal-containing product exposures. METHODS: We performed a chart review and descriptive analysis of 100 randomly selected patients with AGS during 2010-2019. RESULTS: Median age at onset was 53 years, 56% were female, 95% reported White race, 86% reported a history of tick bite, and 75% met the criteria for anaphylaxis based on the involvement of ≥2 organ systems. Those reporting dairy reactions were significantly less likely to report isolated mucocutaneous symptoms (3% vs. 24%; ratio [95% CI]: 0.1 [0.1, 0.3]) than those who tolerated dairy, and were more likely to report gastrointestinal symptoms (79% vs. 59%; ratio [95% CI]: 1.3 [0.7, 2.6]), although this difference was not statistically significant. Dairy-tolerant patients demonstrated higher alpha-gal sIgE titers (as a percentage of total IgE) than dairy-reactive patients (GM 4.1 [95% CI: 2.7, 6.1] vs. GM 2.5 [95% CI: 1.3, 4.8], respectively; ratio -1.6 [95% CI: -1.0, 3.9]). CONCLUSION: While tick exposure is common in the southern United States, nearly all AGS patients reported a tick bite. Gastrointestinal symptoms were prominent among those reporting reactions to dairy. Anaphylaxis was common, underscoring the severity and need to raise awareness of AGS among patients and providers.

Correlations and Timeliness of COVID-19 Surveillance Data Sources and Indicators - United States, October 1, 2020-March 22, 2023.

When the U.S. COVID-19 public health emergency declaration expires on May 11, 2023, national reporting of certain categories of COVID-19 public health surveillance data will be transitioned to other data sources or will be discontinued; COVID-19 hospitalization data will be the only data source available at the county level (1). In anticipation of the transition, national COVID-19 surveillance data sources and indicators were evaluated for purposes of ongoing monitoring. The timeliness and correlations among surveillance indicators were analyzed to assess the usefulness of COVID-19-associated hospital admission rates as a primary indicator for monitoring COVID-19 trends, as well as the suitability of other replacement data sources. During April 2022-March 2023, COVID-19 hospital admission rates from the National Healthcare Safety Network (NHSN)† lagged 1 day behind case rates and 4 days behind percentages of positive test results and COVID-19 emergency department (ED) visits from the National Syndromic Surveillance Program (NSSP). In the same analysis, National Vital Statistics System (NVSS) trends in the percentage of deaths that were COVID-19-associated, which is tracked by date of death rather than by report date, were observable 13 days earlier than those from aggregate death count data, which will be discontinued (1). During October 2020-March 2023, strong correlations were observed between NVSS and aggregate death data (0.78) and between the percentage of positive SARS-CoV-2 test results from the National Respiratory and Enteric Viruses Surveillance System (NREVSS) and COVID-19 electronic laboratory reporting (CELR) (0.79), which will also be discontinued (1). Weekly COVID-19 Community Levels (CCLs) will be replaced with levels of COVID-19 hospital admission rates (low, medium, or high) which demonstrated >99% concordance by county during February 2022-March 2023. COVID-19-associated hospital admission levels are a suitable primary metric for monitoring COVID-19 trends, the percentage of COVID-19 deaths is a timely disease severity indicator, and the percentages of positive SARS-CoV-2 test results from NREVSS and ED visits serve as early indicators for COVID-19 monitoring. Collectively, these surveillance data sources and indicators can support monitoring of the impact of COVID-19 and related prevention and control strategies as ongoing public health priorities.

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration - United States, May 11, 2023.

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).

Tick bite as a risk factor for alpha-gal-specific immunoglobulin E antibodies and development of alpha-gal syndrome.

BACKGROUND: The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal-specific IgE (sIgE) antibodies. OBJECTIVE: To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. METHODS: We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. RESULTS: The patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). CONCLUSION: The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.

Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods - United States, December 2020-January 2022.

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, was first clinically identified in the United States on December 1, 2021, and spread rapidly. By late December, it became the predominant strain, and by January 15, 2022, it represented 99.5% of sequenced specimens in the United States* (1). The Omicron variant has been shown to be more transmissible and less virulent than previously circulating variants (2,3). To better understand the severity of disease and health care utilization associated with the emergence of the Omicron variant in the United States, CDC examined data from three surveillance systems and a large health care database to assess multiple indicators across three high-COVID-19 transmission periods: December 1, 2020-February 28, 2021 (winter 2020-21); July 15-October 31, 2021 (SARS-CoV-2 B.1.617.2 [Delta] predominance); and December 19, 2021-January 15, 2022 (Omicron predominance). The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9-15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020-21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020-21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020-21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage,† which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial.§ This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.

Identification of Presymptomatic and Asymptomatic Cases Using Cohort-Based Testing Approaches at a Large Correctional Facility-Chicago, Illinois, USA, May 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. Correctional and detention facilities are at high risk of experiencing outbreaks. We aimed to evaluate cohort-based testing among detained persons exposed to laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to identify presymptomatic and asymptomatic cases. METHODS: During 1-19 May 2020, 2 testing strategies were implemented in 12 tiers or housing units of the Cook County Jail, Chicago, Illinois. Detained persons were approached to participate in serial testing (n = 137) and offered tests at 3 time points over 14 days (day 1, days 3-5, and days 13-14). The second group was offered a single test and interview at the end of a 14-day quarantine period (day 14 group) (n = 87). RESULTS: 224 detained persons were approached for participation and, of these, 194 (87%) participated in ≥1 interview and 172 (77%) had ≥1 test. Of the 172 tested, 19 were positive for SARS-CoV-2. In the serial testing group, 17 (89%) new cases were detected, 16 (84%) on day 1, 1 (5%) on days 3-5, and none on days 13-14; in the day 14 group, 2 (11%) cases were identified. More than half (12/19; 63%) of the newly identified cases were presymptomatic or asymptomatic. CONCLUSIONS: Our findings highlight the utility of cohort-based testing promptly after initiating quarantine within a housing tier. Cohort-based testing efforts identified new SARS-CoV-2 asymptomatic and presymptomatic infections that may have been missed by symptom screening alone.

A Prospective Cohort Study in Nonhospitalized Household Contacts With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Symptom Profiles and Symptom Change Over Time.

BACKGROUND: Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. METHODS: From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time. RESULTS: We identified 47 contacts, median age 24 (3-75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18-49, and ≥50 years of age, respectively; P = .03). CONCLUSIONS: Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine - United States, September 6, 2020-May 1, 2021.

Throughout the COVID-19 pandemic, older U.S. adults have been at increased risk for severe COVID-19-associated illness and death (1). On December 14, 2020, the United States began a nationwide vaccination campaign after the Food and Drug Administration's Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine. The Advisory Committee on Immunization Practices (ACIP) recommended prioritizing health care personnel and residents of long-term care facilities, followed by essential workers and persons at risk for severe illness, including adults aged ≥65 years, in the early phases of the vaccination program (2). By May 1, 2021, 82%, 63%, and 42% of persons aged ≥65, 50-64, and 18-49 years, respectively, had received ≥1 COVID-19 vaccine dose. CDC calculated the rates of COVID-19 cases, emergency department (ED) visits, hospital admissions, and deaths by age group during November 29-December 12, 2020 (prevaccine) and April 18-May 1, 2021. The rate ratios comparing the oldest age groups (≥70 years for hospital admissions; ≥65 years for other measures) with adults aged 18-49 years were 40%, 59%, 65%, and 66% lower, respectively, in the latter period. These differential declines are likely due, in part, to higher COVID-19 vaccination coverage among older adults, highlighting the potential benefits of rapidly increasing vaccination coverage.

Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018.

BACKGROUND: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown. OBJECTIVE: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States. METHODS: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates. RESULTS: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population. CONCLUSION: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.

Network Characteristics and Visualization of COVID-19 Outbreak in a Large Detention Facility in the United States - Cook County, Illinois, 2020.

Correctional and detention facilities have been disproportionately affected by coronavirus disease 2019 (COVID-19) because of shared space and movement of staff members and detained persons within facilities (1,2). During March 1-April 30, 2020, at Cook County Jail in Chicago, Illinois, >900 COVID-19 cases were diagnosed across all 10 housing divisions, representing 13 unique buildings.† Movement within the jail was examined through network analyses and visualization, a field that examines elements within a network and the connections between them. This methodology has been used to supplement contact tracing investigations for tuberculosis and to understand how social networks contribute to transmission of sexually transmitted infections (3-5). Movements and connections of 5,884 persons (3,843 [65%] detained persons and 2,041 [35%] staff members) at the jail during March 1-April 30 were analyzed. A total of 472 (12.3%) COVID-19 cases were identified among detained persons and 198 (9.7%) among staff members. Among 103,701 shared-shift connections among staff members, 1.4% occurred between persons with COVID-19, a percentage that is significantly higher than the expected 0.9% by random occurrence alone (p<0.001), suggesting that additional transmission occurred within this group. The observed connections among detained persons with COVID-19 were significantly lower than expected (1.0% versus 1.1%, p<0.001) when considering only the housing units in which initial transmission occurred, suggesting that the systematic isolation of persons with COVID-19 is effective at limiting transmission. A network-informed approach can identify likely points of high transmission, allowing for interventions to reduce transmission targeted at these groups or locations, such as by reducing convening of staff members, closing breakrooms, and cessation of contact sports.

Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

Diagnostic Methods Used to Classify Confirmed and Probable Cases of Spotted Fever Rickettsioses - United States, 2010-2015.

Spotted fever rickettsioses (SFR), including Rocky Mountain spotted fever (RMSF), are nationally notifiable diseases in the United States caused by spotted fever group Rickettsia. The annual incidence of SFR increased from 1.7 cases per 1 million persons in 2000 to 13.2 in 2016 (1,2). Although this demonstrates a substantial increase in SFR cases, the actual magnitude of the increase is questionable because the current case definition allows for nonspecific laboratory criteria to support diagnosis (3). To analyze the quality of laboratory data used to support the diagnosis of SFR cases with illness onset during 2010-2015, CDC examined supplementary case report forms. Among 16,807 reported cases, only 167 (1.0%) met the confirmed case definition, and the remaining 16,640 (99.0%) met the probable case definition. The most common supportive laboratory evidence for probable cases was elevated immunoglobulin G (IgG) antibody titer by indirect immunofluorescence assay (IFA), which was reported for 14,784 (88.8%) probable cases. Antibodies to spotted fever group Rickettsia can persist for months or years following infection, making a single antibody titer unreliable for diagnosing incident disease without a convalescent specimen. Increased use of molecular assays and use of paired and appropriately timed IFA IgG testing practices could improve understanding of SFR epidemiology and increase the accuracy of disease incidence estimates.

Human Adenovirus Surveillance - United States, 2003-2016.

Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses in the family Adenoviridae; seven species (A-G) and >60 genotypes are known to cause human infection (1). Clinical manifestations associated with HAdV infection include fever, acute respiratory illness, gastroenteritis, and conjunctivitis. HAdV infection can be severe, particularly among immunocompromised patients, and can cause respiratory failure, disseminated infection, hemorrhagic cystitis, neurologic disease, and death (1,2). Illness tends to occur sporadically and without demonstrated seasonality. Outbreaks of HAdV have been reported globally in communities (3), and in closed or crowded settings, including dormitories, health care settings, and among military recruits, for whom a vaccine against HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) has been developed (4,5). CDC summarized HAdV detections voluntarily reported through the National Adenovirus Type Reporting System (NATRS) after initiation of surveillance in 2014 to describe trends in reported HAdVs circulating in the United States. Reporting laboratories were also encouraged to report available results for specimens collected before surveillance began. Overall, the number of reporting laboratories and HAdV type identifications reported to NATRS has increased substantially from the start of official reporting in 2014 through 2016; this report describes specimens collected during 2003-2016. The most commonly reported HAdV types were HAdV type 3 (HAdV-3) and HAdV type 2 (HAdV-2), although HAdV types reported fluctuated considerably from year to year. In the United States, information on recently circulating HAdV types is needed to inform diagnostic and surveillance activities by clinicians and public health practitioners. Routine reporting to NATRS by all U.S. laboratories with the capacity to type HAdVs could help strengthen this surveillance system.

Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia.

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014-January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices.

Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis.

RATIONALE: Persons with cystic fibrosis (CF) are at high risk of nontuberculous mycobacterial (NTM) infection, with treatment requiring prolonged multidrug regimens that include macrolides. Although macrolides, specifically azithromycin, are used in the management of patients with CF with chronic Pseudomonas, macrolide-resistant NTM infections are of growing concern. OBJECTIVES: To evaluate the relationship between chronic macrolide use and NTM infection among patients with CF included in the 2011 CF Patient Registry (CFPR). METHODS: We performed a nested case-control study: incident NTM cases were persons aged more than 5 years with at least one positive culture for NTM in 2011. Controls were persons with negative cultures in 2010 and 2011. MEASUREMENTS AND MAIN RESULTS: The 2011 CFPR included 27,112 patients; 5,403 (20%) were cultured for mycobacteria in 2010-2011 and met all inclusion criteria. Of these, 191 (4%) were NTM-positive in 2011 only (cases); 5,212 (96%) were NTM-negative in 2010 and 2011 (control subjects). Among the cases, 122 (64%) were culture-positive for Mycobacterium avium complex (MAC) and 69 (36%) for M. abscessus. Azithromycin use in 2010 was less frequently reported among MAC cases (57%; odds ratio = 0.7, P < 0.05) and M. abscessus cases (51%; odds ratio = 0.5, P < 0.01) than in control subjects (66%). Among adolescents and adults, patients with the greatest number of years on chronic macrolides were the least likely to develop incident NTM in 2011 (P < 0.01). CONCLUSIONS: Patients with incident NTM infections from either MAC or M. abscessus were less likely to have had chronic azithromycin treatment in the past year. However, because macrolide monotherapy may lead to macrolide resistance, routine screening for NTM should be considered for persons with CF.

Correction: Inferring school district learning modalities during the COVID-19 pandemic with a hidden Markov model.

[This corrects the article DOI: 10.1371/journal.pone.0292354.].

Inferring school district learning modalities during the COVID-19 pandemic with a hidden Markov model.

During the COVID-19 pandemic, many public schools across the United States shifted from fully in-person learning to alternative learning modalities such as hybrid and fully remote learning. In this study, data from 14,688 unique school districts from August 2020 to June 2021 were collected to track changes in the proportion of schools offering fully in-person, hybrid and fully remote learning over time. These data were provided by Burbio, MCH Strategic Data, the American Enterprise Institute's Return to Learn Tracker and individual state dashboards. Because the modalities reported by these sources were incomplete and occasionally misaligned, a model was needed to combine and deconflict these data to provide a more comprehensive description of modalities nationwide. A hidden Markov model (HMM) was used to infer the most likely learning modality for each district on a weekly basis. This method yielded higher spatiotemporal coverage than any individual data source and higher agreement with three of the four data sources than any other single source. The model output revealed that the percentage of districts offering fully in-person learning rose from 40.3% in September 2020 to 54.7% in June of 2021 with increases across 45 states and in both urban and rural districts. This type of probabilistic model can serve as a tool for fusion of incomplete and contradictory data sources in order to obtain more reliable data in support of public health surveillance and research efforts.

Impact of the COVID-19 Vaccination Program on case incidence, emergency department visits, and hospital admissions among children aged 5-17 Years during the Delta and Omicron Periods-United States, December 2020 to April 2022.

BACKGROUND: In the United States, national ecological studies suggest a positive impact of COVID-19 vaccination coverage on outcomes in adults. However, the national impact of the vaccination program on COVID-19 in children remains unknown. To determine the association of COVID-19 vaccination with U.S. case incidence, emergency department visits, and hospital admissions for pediatric populations during the Delta and Omicron periods. METHODS: We conducted an ecological analysis among children aged 5-17 and compared incidence rate ratios (RRs) of COVID-19 cases, emergency department visits, and hospital admissions by pediatric vaccine coverage, with jurisdictions in the highest vaccine coverage quartile as the reference. RESULTS: RRs comparing states with lowest pediatric vaccination coverage to the highest pediatric vaccination coverage were 2.00 and 0.64 for cases, 2.96 and 1.11 for emergency department visits, and 2.76 and 1.01 for hospital admissions among all children during the Delta and Omicron periods, respectively. During the 3-week peak period of the Omicron wave, only children aged 12-15 and 16-17 years in the states with the lowest versus highest coverage, had a significantly higher rate of emergency department visits (RR = 1.39 and RR = 1.34, respectively). CONCLUSIONS: COVID-19 vaccines were associated with lower case incidence, emergency department visits and hospital admissions among children during the Delta period but the association was weaker during the Omicron period. Pediatric COVID-19 vaccination should be promoted as part of a program to decrease COVID-19 impact among children; however, vaccine effectiveness may be limited when available vaccines do not match circulating viral variants.