Showing papers by "Timothy M. Uyeki published in 2020"

First Case of 2019 Novel Coronavirus in the United States.

Abstract: An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

A minimal common outcome measure set for COVID-19 clinical research

Abstract: Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020.

Abstract: SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged ≥65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation† (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.

Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.

Abstract: An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.

First 12 patients with coronavirus disease 2019 (COVID-19) in the United States

Abstract: Introduction More than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. Methods We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20–February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results Among the 12 patients, median age was 53 years (range: 21–68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. Conclusions In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Fifty Years of Influenza A(H3N2) Following the Pandemic of 1968.

Abstract: In 2018, the world commemorated the centennial of the 1918 influenza A(H1N1) pandemic, the deadliest pandemic in recorded history; however, little mention was made of the 50th anniversary of the 1968 A(H3N2) pandemic. Although pandemic morbidity and mortality were much lower in 1968 than in 1918, influenza A(H3N2) virus infections have become the leading cause of seasonal influenza illness and death over the last 50 years, with more than twice the number of hospitalizations from A(H3N2) as from A(H1N1) during the past six seasons. We review the emergence, progression, clinical course, etiology, epidemiology, and treatment of the 1968 pandemic and highlight the short- and long-term impact associated with A(H3N2) viruses. The 1968 H3N2 pandemic and its ongoing sequelae underscore the need for improved seasonal and pandemic influenza prevention, control, preparedness, and response efforts.

Clinical Characteristics of Patients Hospitalized with Coronavirus Disease, Thailand.

Abstract: Among 11 patients in Thailand infected with severe acute respiratory syndrome coronavirus 2, we detected viral RNA in upper respiratory specimens a median of 14 days after illness onset and 9 days after fever resolution. We identified viral co-infections and an asymptomatic person with detectable virus RNA in serial tests. We describe implications for surveillance.

Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households

Abstract: Few data are available on the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission In this cluster randomized trial of 259 people with confirmed influenza v

Predictors at admission of mechanical ventilation and death in an observational cohort of adults hospitalized with COVID-19.

Abstract: BACKGROUND: Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. METHODS: We conducted a retrospective observational cohort investigation of 297 adults admitted to eight academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI) for predictors of invasive mechanical ventilation (IMV) and death. RESULTS: Compared with age <45 years, ages 65-74 years and ≥75 years were predictors of IMV (aOR 3.12, CI 1.47-6.60; aOR 2.79, CI 1.23-6.33) and the strongest predictors for death (aOR 12.92, CI 3.26-51.25; aOR 18.06, CI 4.43-73.63). Comorbidities associated with death (aORs from 2.4 to 3.8, p <0.05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Pre-hospital use vs. non-use of angiotensin receptor blockers (aOR 2.02, CI 1.03-3.96) and dihydropyridine calcium channel blockers (aOR 1.91, CI 1.03-3.55) were associated with death. CONCLUSIONS: After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

Remote Household Observation for Non-influenza Respiratory Viral Illness.

Abstract: BACKGROUND: Non-influenza respiratory viruses are responsible for a substantial burden of disease in the United States. Household transmission is thought to contribute significantly to subsequent transmission through the broader community. In the context of the COVID-19 pandemic, contactless surveillance methods are of particular importance. METHODS: From November 2019 to April 2020, 303 households in the Seattle area were remotely monitored in a prospective longitudinal study for symptoms of respiratory viral illness. Enrolled participants reported weekly symptoms and submitted respiratory samples by mail in the event of an acute respiratory illness (ARI). Specimens were tested for fourteen viruses, including SARS-CoV-2, using RT-PCR. Participants completed all study procedures at home without physical contact with research staff. RESULTS: In total, 1171 unique participants in 303 households were monitored for ARI. Of participating households, 128 (42%) included a child aged <5 years and 202 (67%) included a child aged 5-12 years. Of the 678 swabs collected during the surveillance period, 237 (35%) tested positive for one or more non-influenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in three households. CONCLUSIONS: This study highlights the circulation of respiratory viruses within households during the winter months during the emergence of the SARS-CoV-2 pandemic. Contactless methods of recruitment, enrollment and sample collection were utilized throughout this study, and demonstrate the feasibility of home-based, remote monitoring for respiratory infections.

Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysis.

Abstract: Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection. We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses. Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0–0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4–1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7–3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0–0.5%) (p < 0.05). Seroprevalence was higher in poultry-exposed populations (range 0–1.9%) if such studies utilized antigenically similar A(H5N1) virus antigens in assays to A(H5N1) viruses circulating among poultry. These low seroprevalences suggest that subclinical and clinically mild human A(H5N1) virus infections are uncommon. Standardized serological survey and laboratory methods are needed to fully understand the extent and risk of human A(H5N1) virus infections.

Evaluation of potential risk of transmission of avian influenza A viruses at live bird markets in response to unusual crow die-offs in Bangladesh.

Abstract: In response to unusual crow die‐offs from avian influenza A(H5N1) virus infection during January‐February 2017 in Dhaka, Bangladesh, a One Health team assessed potential infection risks in live bird markets (LBMs). Evidence of aerosolized avian influenza A viruses was detected in LBMs and in the respiratory tracts of market workers, indicating exposure and potential for infection. This study highlighted the importance of surveillance platforms with a coordinated One Health strategy to investigate and mitigate zoonotic risk.

Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial.

Abstract: Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings. This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends. ClinicalTrials.gov NCT04141917 . Registered 28 October 2019. Trial sponsor: University of Washington.

Baloxavir for Postexposure Prophylaxis against Influenza in Households

Abstract: In the United States, antiviral treatment of influenza is recommended as soon as possible in hospitalized patients and in outpatients who are at increased risk for influenza complications or have p...

Serological evidence of human infection with avian influenza A(H7N9) virus: a systematic review and meta-analysis.

Abstract: Background The extent of human infections with avian influenza A(H7N9) virus, including mild and asymptomatic infections, is uncertain. Methods We performed a systematic review and meta-analysis of serosurveys for avian influenza A(H7N9) virus infections in humans published during 2013-2020. Three seropositive definitions were assessed to estimate pooled seroprevalence, seroconversion rate and seroincidence by types of exposures. We applied a scoring system to assess the quality of included studies. Results Of 31 included studies, pooled seroprevalence of A(H7N9)-virus antibodies from all participants was 0.02%, with poultry workers, close contacts, and general populations having seroprevalence of 0.1%, 0.2% and 0.02% based on the WHO-recommended definition, respectively. Although most infections were asymptomatic, evidence of infection was highest in poultry workers (5% seroconversion, 19.1% seroincidence per 100 person-years). Use of different virus clades did not significantly affect seroprevalence estimates. Most serological studies were of low to moderate quality and did not follow standardized seroepidemiological protocols or WHO-recommended laboratory methods. Conclusions Human infections with avian influenza A(H7N9) virus have been uncommon, especially for general populations. Workers with occupational exposures to poultry and close contacts of A(H7N9) human cases had low risks of infection.

621: data collection during public health emergencies: lessons learned over three influenza seasons

Abstract: Introduction/Hypothesis: Limitations in the rapid collection of patient-level data during public health emergencies remain a national strategic vulnerability. Over a 3-year period, we developed a consensus, electronic case report form (eCRF) and tested the feasibility of nationwide data collection for intensive care unit (ICU) patients with influenza. Methods: Twelve hospitals in the US implemented an observational protocol to collect data on ICU patients with laboratoryconfirmed influenza over 2-week periods. In year 1, data were collected retrospectively over hospital-identified timeframes. In years 2-3, data were collected prospectively during designated timeframes. In year 1, 80 clinical data elements were collected. In years 2-3, 151 clinical data elements were collected in a 2-tier system, with tier-1 data collected within 48-hours of admission and tier-2 data within 14 days. Descriptive statistics were calculated. Results: Over 3 years, data for 198 patients were collected across 12 sites (53% male, 91% adult). Year 1 data were retrospectively captured (n=74); year 2 (n=70) and year 3 (n=54) data were prospectively captured. 64% were mechanically ventilated, with consistency over the 3 years. 11% were on ECMO (11%, 4%, 19% by year). 90% received antiviral therapy within 48-hours (oseltamivir 98%). 87% received antibacterial drugs (93%, 82%, 85% by year). Antifungals were administered to 16% and corticosteroids to 41%. 38% were discharged home (32%, 50%, 30% by year). 21% remained in the hospital (19%, 19%, 28% by year). 16% died (20%, 9%, 20% by year). Conclusions: Data collection method and flu season timing varied over the 3-year period, but consistency of results across time suggest several lessons. A consensus eCRF for influenza has been developed that can be broadly applied with consistent data collection allowing for clinically relevant comparisons across time and location. There were important variations in treatment of lifethreatening influenza that could have affected outcomes over time; the reasons for treatment variance are not known and require study. For example, mechanical ventilation as supportive care was consistent throughout the 3-year period, while ECMO rates and treatment with corticosteroids varied. Next steps are automated data extraction and expanded data collection windows.