Liver abnormalities following SARS-CoV-2 infection in children 1 to 10 years of age.

OBJECTIVE: Beginning in October 2021 in the USA and elsewhere, cases of severe paediatric hepatitis of unknown aetiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading aetiological suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DESIGN: We conducted a study using retrospective cohorts of deidentified, aggregated data from the electronic health records of over 100 million patients contributed by US healthcare organisations. RESULTS: Compared with propensity score matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (HR (95% CI) 2.16 (1.74 to 2.69)) or total bilirubin (HR (95% CI) 3.02 (1.91 to 4.78)), or new diagnoses of liver diseases (HR (95% CI) 1.67 (1.21 to 2.30)) from 1 to 6 months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years) or illness requiring hospitalisation all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. CONCLUSION: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver.

Risk for diagnosis or treatment of mood or anxiety disorders in adults after SARS-CoV-2 infection, 2020-2022.

COVID-19 is associated with increased risks for mood or anxiety disorders, but it remains uncertain how the association evolves over time or which patient groups are most affected. We conducted a retrospective cohort study using a nationwide database of electronic health records to determine the risk of depressive or anxiety disorder diagnoses after SARS-CoV-2 infection by 3-month blocks from January 2020 to April 2022. The study population comprised 822,756 patients (51.8% female; mean age 42.8 years) with COVID-19 and 2,034,353 patients with other respiratory tract infections (RTIs) (53.5% female, mean age 30.6 years). First time diagnoses of depressive or anxiety disorders 14 days to 3 months after infection, as well as new or new plus recurrent prescriptions of antidepressants or anxiolytics, were compared between propensity score matched cohorts using Kaplan-Meier survival analysis, including hazard ratio (HR) and 95% confidence interval (CI). Risk of a new diagnosis or prescription was also stratified by age, sex, and race to better characterize which groups were most affected. In the first three months of the pandemic, patients infected with SARS-CoV-2 had significantly increased risk of depression or anxiety disorder diagnosis (HR 1.65 [95% CI, 1.30-2.08]). October 2021 to January 2022 (HR, 1.12 [95% CI, 1.06-1.18]) and January to April 2022 (HR, 1.08 [95% CI, 1.01-1.14]). Similar temporal patterns were observed for antidepressant and anxiolytic prescriptions, when the control group was patients with bone fracture, when anxiety and depressive disorders were considered separately, when recurrent depressive disorder was tested, and when the test period was extended to 6 months. COVID-19 patients ≥65 years old demonstrated greatest absolute risk at the start of the pandemic (6.8%), which remained consistently higher throughout the study period (HR, 1.20 [95% CI, 1.13-1.27]), and overall, women with COVID-19 had greater risk than men (HR 1.35 [95% CI 1.30-1.40]).

Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age.

Objective: Beginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. Design: We conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. Results: Compared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. Conclusion: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. What is already known on this topic: Clusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent. What this study adds: SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. How this study might affect research practice or policy: Despite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.

Association of Recent SARS-CoV-2 Infection With New-Onset Alcohol Use Disorder, January 2020 Through January 2022.

Importance: The COVID-19 pandemic affects many diseases, including alcohol use disorders (AUDs). As the pandemic evolves, understanding the association of a new diagnosis of AUD with COVID-19 over time is required to mitigate negative consequences. Objective: To examine the association of COVID-19 infection with new diagnosis of AUD over time from January 2020 through January 2022. Design, Setting, and Participants: In this retrospective cohort study of electronic health records of US patients 12 years of age or older, new diagnoses of AUD were compared between patients with COVID-19 and patients with other respiratory infections who had never had COVID-19 by 3-month intervals from January 20, 2020, through January 27, 2022. Exposures: SARS-CoV-2 infection or non-SARS-CoV-2 respiratory infection. Main Outcomes and Measures: New diagnoses of AUD were compared in COVID-19 and propensity score-matched control cohorts by hazard ratios (HRs) and 95% CIs from either 14 days to 3 months or 3 to 6 months after the index event. Results: This study comprised 1 201 082 patients with COVID-19 (56.9% female patients; 65.7% White; mean [SD] age at index, 46.2 [18.9] years) and 1 620 100 patients with other respiratory infections who had never had COVID-19 (60.4% female patients; 71.1% White; mean [SD] age at index, 44.5 [20.6] years). There was a significantly increased risk of a new diagnosis of AUD in the 3 months after COVID-19 was contracted during the first 3 months of the pandemic (block 1) compared with control cohorts (HR, 2.53 [95% CI, 1.82-3.51]), but the risk decreased to nonsignificance in the next 3 time blocks (April 2020 to January 2021). The risk for AUD diagnosis increased after infection in January to April 2021 (HR, 1.30 [95% CI, 1.08-1.56]) and April to July 2021 (HR, 1.80 [95% CI, 1.47-2.21]). The result became nonsignificant again in blocks 7 and 8 (COVID-19 diagnosis between July 2021 and January 2022). A similar temporal pattern was seen for new diagnosis of AUD 3 to 6 months after infection with COVID-19 vs control index events. Conclusions and Relevance: Elevated risk for AUD after COVID-19 infection compared with non-COVID-19 respiratory infections during some time frames may suggest an association of SARS-CoV-2 infection with the pandemic-associated increase in AUD. However, the lack of excess hazard in most time blocks makes it likely that the circumstances surrounding the pandemic and the fear and anxiety they created also were important factors associated with new diagnoses of AUD.

COVID-19 in Pregnancy: Occupations With Higher Density of Population Exposure Associated With More Severe Disease.

OBJECTIVE: To define the symptomatology of SARS-CoV-2 infection in pregnancy and associations between occupation, sociodemographic factors, and comorbidities with the severity of COVID-19 disease in pregnancy in all trimesters, regardless of hospitalization. METHODS: We studied a retrospective cohort of a public health surveillance sample of persons with COVID-19 infection diagnosed during pregnancy. Data was collected March 2020 to August 2020 regarding symptoms, disease severity, comorbidities, obstetric history, and occupation. RESULTS: One hundred sixty-three individuals were identified. Constitutional (64%) and lower respiratory symptoms (61%) were most common. Seventeen individuals (13.6%) were hospitalized, and one person (0.7%) died due to COVID-19. Risk factors for severe disease were age and an occupation that had high intensity exposure to people. CONCLUSIONS: Occupational exposure is a risk factor for severe COVID-19 disease in pregnancy, justifying policy measures to ensure protection of this vulnerable population.

Characterization of community-wide transmission of SARS-CoV-2 in congregate living settings and local public health-coordinated response during the initial phase of the COVID-19 pandemic.

BACKGROUND: Clusters of COVID-19 cases amplify the pandemic and are critical targets for intervention, but comprehensive cluster-level data are not collected systematically by federal or most state public health entities. This analysis characterizes COVID-19 clusters among vulnerable populations housed in congregate living settings across an entire community and describes early mitigation efforts. METHODS: The Cuyahoga County Board of Health identified and interviewed COVID-19 cases and exposed contacts, assessing possible connections to congregate living facilities within its jurisdiction from March 7, 2020, to May 15, 2020, during the first phase of the pandemic, while state of Ohio stay-at-home orders were in effect. A multi-disciplinary team-based response network was mobilized to support active case finding and develop facility-focused containment strategies. RESULTS: We identified a cascade of 45 COVID-19 clusters across community facilities (corrections, nursing, assisted living, intermediate care, extended treatment, shelters, group homes). Attack rates were highest within small facilities (P < .01) and large facilities requiring extensive support to implement effective containment measures. For 25 clusters, we identified an index case who frequently (88%) was a healthcare worker. Engagement of clinical, community, and government partners through public health coordination efforts created opportunities to rapidly develop and coordinate effective response strategies to support the facilities facing the dawning impact of the pandemic. CONCLUSIONS: Active cluster investigations can uncover the dynamics of community transmission affecting both residents of congregate settings and their caregivers and help to target efforts toward populations with ongoing challenges in access to detection and control resources.

Human infection with avian influenza A(H7N2) virus-Virginia, 2002.

BACKGROUND: In March 2002, an outbreak of low-pathogenic avian influenza (LPAI) A(H7N2) was detected among commercial poultry operations in Virginia. METHODS: We performed a serosurvey of 80 government workers involved in efforts to control the outbreak. RESULTS: One study participant who assisted with disposal of infected birds tested positive for neutralizing antibodies to influenza A(H7N2) by microneutralization assay and H7-specific IgM antibodies by enzyme-linked immunosorbent assay (ELISA). The acute infection was temporally associated with an influenza-like illness that resolved without hospitalization. CONCLUSION: This study documents the earliest evidence of human infection with an H7 influenza virus of the North American lineage.

Seasonal influenza morbidity estimates obtained from telephone surveys, 2007.

OBJECTIVES: We assessed telephone surveys as a novel surveillance method, comparing data obtained by telephone with existing national influenza surveillance systems, and evaluated the utility of telephone surveys. METHODS: We used the 2007 Behavioral Risk Factor Surveillance System (BRFSS) and the 2007 National Immunization Survey-Adult (NIS-Adult) to estimate the incidence of influenza-like illness (ILI), medically attended ILI, provider-diagnosed influenza, influenza testing, and treatment of influenza with antiviral medications during the 2006-2007 influenza season. RESULTS: With the January-May BRFSS, among persons aged 18 years and older, the cumulative incidence of seasonal ILI and provider-diagnosed influenza was 37.9 and 5.7 adults per 100 persons, respectively. Monthly medically attended ILI and provider-diagnosed influenza among adults were temporally associated with influenza activity, as documented by national surveillance. With the NIS-Adult survey data, estimated provider-diagnosed influenza, influenza testing, and antiviral treatment were 2.8%, 1.4%, and 0.6%, respectively. CONCLUSIONS: Our telephone interview-based estimates of influenza morbidity were consistent with those from national influenza surveillance systems. Telephone surveys may provide an alternative method by which population-based influenza morbidity information can be gathered.

Transmission of influenza A viruses between pigs and people, Iowa, 2002-2004.

BACKGROUND: Triple-reassortant (tr) viruses of human, avian, and swine origin, including H1N1, H1N2, and H3N2 subtypes, emerged in North American swine herds in 1998 and have become predominant. While sporadic human infections with classical influenza A (H1N1) and with tr-swine influenza viruses have been reported, relatively few have been documented in occupationally exposed swine workers (SW). METHODS: We conducted a 2-year (2002-2004) prospective cohort study of transmission of influenza viruses between pigs and SW from a single pork production company in Iowa. Respiratory samples were collected and tested for influenza viruses from SW and from pigs under their care through surveillance for influenza-like illnesses (ILI). Serial blood samples from study participants were tested by hemagglutination inhibition (HI) for antibody seroconversion against human and swine influenza viruses (SIV), and antibody seroprevalence was compared to age-matched urban Iowa blood donors. RESULTS: During the first year, 15 of 88 SW had ILI and were sampled; all were culture-negative for influenza. During the second year, 11 of 76 SW had ILI and were sampled; one was culture-positive for a human seasonal H3N2 virus. Among 20 swine herd ILI outbreaks sampled, influenza A virus was detected by rRT-PCR from 17 with 11 trH1N1 and five trH3N2 virus isolates cultured. During both years, HI geometric mean titers were significantly higher among SW compared to blood donor controls for three SIV: classical swine Sw/WI/238/97 (H1N1), tr Sw/IN/9K035/99 (H1N2), and trSw/IA/H02NJ56371/02 (H1N1)] (P < 0·0001). CONCLUSIONS: SW had serologic evidence for infection with both swine and human influenza viruses and were exposed to diverse influenza virus strains circulating in pigs. Influenza virus surveillance among pigs and SW should be encouraged to better understand cross-species transmission and diversity of influenza viruses at the human-swine interface.

Vaccine effectiveness against medically attended, laboratory-confirmed influenza among children aged 6 to 59 months, 2003-2004.

OBJECTIVES: Influenza is a leading cause of illness among children. Studies rarely have measured influenza vaccine effectiveness among young children, particularly when antigenic match between vaccine and circulating viruses is suboptimal. We assessed vaccine effectiveness against medically attended, laboratory-confirmed influenza for children who were aged 6 to 59 months during the 2003-2004 influenza season. METHODS: In a case-control study that was conducted in a single pediatric practice, case patients who were aged 6 to 59 months and had laboratory-confirmed influenza were age matched 1:2 to eligible control subjects. Vaccination status was ascertained as of the date of the case patient's symptom onset. Conditional logistic regression was used to calculate vaccine effectiveness, adjusting for underlying medical conditions and health care usage. RESULTS: We identified 290 influenza case patients who were seen for medical care from November 1, 2003, to January 31, 2004. Vaccine effectiveness among fully vaccinated children, compared with unvaccinated children, was 49%. Partially vaccinated children who were aged 6 to 23 months had no significant reduction in influenza (vaccine effectiveness: -70%), but partially vaccinated children who were aged 24 to 59 months had a significant (65%) reduction in influenza, compared with unvaccinated children. CONCLUSIONS: Full vaccination provided measurable protection against laboratory-confirmed influenza among children who were aged 6 to 59 months during a season with suboptimal vaccine match. No vaccine effectiveness was identified with partial vaccination among children who were aged 6 to 23 months, affirming that children need to be fully vaccinated to obtain protective effects. These results strengthen the evidence of the vaccine's ability to reduce substantially the burden of disease in this age group.

Human metapneumovirus infection among children, Bangladesh.

We confirmed circulation of human metapneumovirus (HMPV) among children with febrile and respiratory illness in an urban slum in Dhaka, Bangladesh, during active surveillance in 2001. HMPV was the most common single virus identified among febrile children and appears to contribute to the high rates of illness in this population.

Impact of influenza on young children and the shaping of United States influenza vaccine policy.

BACKGROUND: In 2002 the Advisory Committee on Immunization Practices (ACIP) began encouraging annual influenza vaccination of children 6 to 23 months of age, when feasible. METHODS: Literature and issues related to annual influenza vaccination of young children were reviewed. RESULTS: The ACIP first encouraged influenza vaccination of children 6 to 23 months of age in 2002 because recent studies showed that influenza-related hospital admissions were substantially higher among healthy children <2 years than among healthy older children or young adults. However, the ACIP deferred a full recommendation for several reasons, including limited safety and efficacy data on trivalent inactivated influenza virus in the 6- to 23-month age group, the need for more education of parents and physicians and concerns over the stability and adequacy of the vaccine supply. CONCLUSIONS: The risk of hospital admission from influenza-related causes is high in young children and similar to the risk in the elderly and other high risk groups for whom annual influenza vaccination is already recommended. Data from additional studies, especially those on vaccine safety and efficacy, will be important for proceeding to a full recommendation for annual influenza vaccination of children 6 to 23 months.

The West Nile virus epidemic in Arkansas, 2002: the Arkansas Department of Health response.

In June 2002, the Arkansas Department of Health anticipated a West Nile virus epidemic based on diagnoses in birds and increasing reports of human disease cases in neighboring states. Department officials activated an emergency operations center (EOC) dedicated to human West Nile virus surveillance. As a result, 43 cases (33 West Nile meningoencephalitis and 10 West Nile fever) and five (12%) deaths were confirmed from 16 counties. For all cases, the median age was 54 years (range: 2-93 years). County-specific incidence of West Nile meningoencephalitis ranged from 0.6-15.9 cases per 100,000 people. The implemented system for enhanced West Nile virus surveillance will serve as a model for future epidemic years.

Enhanced drop-in syndromic surveillance in New York City following September 11, 2001.

After the 2001 World Trade Center disaster, the New York City Department of Health was under heightened alert for bioterrorist attacks in the city. An emergency department (ED) syndromic surveillance system was implemented with the assistance of the Centers for Disease Control and Prevention to ensure early recognition of an increase or clustering of disease syndromes that might represent a disease outbreak, whether natural or intentional. The surveillance system was based on data collected 7 days a week at area EDs. Data collected were translated into syndromes, entered into an electronic database, and analyzed for aberrations in space and time within 24 hours. From September 14-27, personnel were stationed at 15 EDs on a 24-hour basis (first staffing period); from September 29-October 12, due to resource limitations, personnel were stationed at 12 EDs on an 18-hour basis (second staffing period). A standardized form was used to obtain demographic information and classify each patient visit into 12 syndrome categories. Seven of these represented early manifestations of bioterrorist agents. Data transfer and analysis for time and space clustering (alarms) by syndrome and age occurred daily. Retrospective analyses examined syndrome trends, differences in reporting between staffing periods, and the staff's experience during the project. A total of 67,536 reports were received. The system captured 83.9% of patient visits during the first staffing period, and 60.8% during the second staffing period (P < 0.01). Five syndromes each accounted for more than 1% of visits: trauma, asthma, gastrointestinal illness, upper/lower respiratory infection with fever, and anxiety. Citywide temporal alarms occurred eight times for three of the major bioterrorism-related syndromes. Spatial clustering alarms occurred 16 times by hospital location and 9 times by ZIP code for the same three syndromes. No outbreaks were detected. On-site staffing to facilitate data collection and entry, supported by daily analysis of ED visits, is a feasible short-term approach to syndromic surveillance during high-profile events. The resources required to operate such a system, however, cannot be sustained for the long term. This system was changed to an electronic-based ED syndromic system using triage log data that remains in operation.