Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged <10 Years - United States, October 2021-June 2022.

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

Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children - United States, 2017-2022.

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

Adapting the Surveillance Platform for Enteric and Respiratory Infectious Organisms at United States Veterans Affairs Medical Centers (SUPERNOVA) for COVID-19 Among Hospitalized Adults: Surveillance Protocol.

Introduction: Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) rapidly initiated COVID-19 surveillance by leveraging existing hospital networks to assess disease burden among hospitalized inpatients and inform prevention efforts. Materials and Methods: The Surveillance Platform for Enteric and Respiratory Infectious Organisms at Veterans Affairs Medical Centers (SUPERNOVA) is a network of five United States Veterans Affairs Medical Centers which serves nearly 400,000 Veterans annually and conducts laboratory-based passive and active monitoring for pathogens associated with acute gastroenteritis and acute respiratory illness among hospitalized Veterans. This paper presents surveillance methods for adapting the SUPERNOVA surveillance platform to prospectively evaluate COVID-19 epidemiology during a public health emergency, including detecting, characterizing, and monitoring patients with and without COVID-19 beginning in March 2020. To allow for case-control analyses, patients with COVID-19 and patients with non-COVID-19 acute respiratory illness were included. Results: SUPERNOVA included 1,235 participants with COVID-19 and 707 participants with other acute respiratory illnesses hospitalized during February through December 2020. Most participants were male (93.1%), with a median age of 70 years, and 45.8% non-Hispanic Black and 32.6% non-Hispanic White. Among those with COVID-19, 28.2% were transferred to an intensive care unit, 9.4% received invasive mechanical ventilation, and 13.9% died. Compared with controls, after adjusting for age, sex, and race/ethnicity, COVID-19 case-patients had significantly higher risk of mortality, respiratory failure, and invasive mechanical ventilation, and longer hospital stays. Discussion: Strengths of the SUPERNOVA platform for COVID-19 surveillance include the ability to collect and integrate multiple types of data, including clinical and illness outcome information, and SARS-CoV-2 laboratory test results from respiratory and serum specimens. Analysis of data from this platform also enables formal comparisons of participants with and without COVID-19. Surveillance data collected during a public health emergency from this key U.S. population of Veterans will be useful for epidemiologic investigations of COVID-19 spectrum of disease, underlying medical conditions, virus variants, and vaccine effectiveness, according to public health priorities and needs.

COVID-19-Related Hospitalization Rates and Severe Outcomes Among Veterans From 5 Veterans Affairs Medical Centers: Hospital-Based Surveillance Study.

BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the United States. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, are needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among US veterans by using a multisite surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers located in Atlanta, Bronx, Houston, Palo Alto, and Los Angeles, collectively serving more than 396,000 patients annually. From February 27 to July 17, 2020, we actively identified inpatient cases with COVID-19 by screening admitted patients and reviewing their laboratory test results. We then manually abstracted the patients' medical charts for demographics, underlying medical conditions, and clinical outcomes. Furthermore, we calculated hospitalization incidence and incidence rate ratios, as well as relative risk for invasive mechanical ventilation, intensive care unit admission, and case fatality rate after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed, hospitalized COVID-19 cases. The median age of the patients was 70 years, with 65.7% (408/621) aged ≥65 years and 94% (584/621) male. Most COVID-19 diagnoses were among non-Hispanic Black (325/621, 52.3%) veterans, followed by non-Hispanic White (153/621, 24.6%) and Hispanic or Latino (112/621, 18%) veterans. Hospitalization rates were the highest among veterans who were ≥85 years old, 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 those aged 18-29 years (95% CI: 5.7-34.6), whereas Hispanic or Latino and Black veterans had a 4.6- and 4.2-fold increased rate of hospitalization, respectively, compared with non-Hispanic White veterans (95% CI: 3.6-5.9). Overall, 11.6% (72/621) of the patients required invasive mechanical ventilation, 26.6% (165/621) were admitted to the intensive care unit, and 16.9% (105/621) died in the hospital. The adjusted relative risk for invasive mechanical ventilation and admission to the intensive care unit did not differ by age group or race and ethnicity, but veterans aged ≥65 years 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 the 5 Veterans Affairs Medical Centers across the United States demonstrated higher hospitalization rates and severe outcomes among older veterans, as well as higher hospitalization rates among Hispanic or Latino and non-Hispanic Black veterans than among non-Hispanic White veterans. These findings highlight the need for targeted prevention and timely treatment for veterans, with special attention to older aged, Hispanic or Latino, and non-Hispanic Black veterans.

First Mildly Ill, Nonhospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States-Maricopa County, Arizona, 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

Risk for In-Hospital Complications Associated with COVID-19 and Influenza - Veterans Health Administration, United States, October 1, 2018-May 31, 2020.

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.

Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.