Nausea, Vomiting, and Diarrhea Are Common in Community-Acquired Acute Viral Respiratory Illness.

BACKGROUND: Gastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes. METHODS: We collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018-2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher's exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression. RESULTS: In 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms. CONCLUSION: In this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

Remote Household Observation for Noninfluenza Respiratory Viral Illness.

BACKGROUND: Noninfluenza 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 coronavirus disease 2019 (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 14 viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using reverse-transcription polymerase chain reaction. 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 1 or more noninfluenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in 3 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.

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.

INTRODUCTION: 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. METHODS AND ANALYSIS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT04141917 . Registered 28 October 2019. Trial sponsor: University of Washington.

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

BACKGROUND: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. OBJECTIVE: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. DESIGN: Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917). SETTING: 14 homeless shelters in King County, Washington. PARTICIPANTS: A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. INTERVENTION: 2 strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing ("surge testing") events. MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. RESULTS: Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. LIMITATION: Selection bias due to voluntary participation and a relatively small case count. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. PRIMARY FUNDING SOURCE: Gates Ventures.

Cross-Sectional Prevalence of SARS-CoV-2 Among Skilled Nursing Facility Employees and Residents Across Facilities in Seattle.

BACKGROUND: Skilled nursing facilities (SNFs) are high-risk settings for SARS-CoV-2 transmission. Infection rates among employees are infrequently described. OBJECTIVE: To describe SARS-CoV-2 rates among SNF employees and residents during a non-outbreak time period, we measured cross-sectional SARS-CoV-2 prevalence across multiple sites in the Seattle area. DESIGN: SARS-CoV-2 testing was performed for SNF employees and residents using quantitative real-time reverse transcription polymerase chain reaction. A subset of employees completed a sociodemographic and symptom questionnaire. PARTICIPANTS: Between March 29 and May 13, 2020, we tested 1583 employees and 1208 residents at 16 SNFs for SARS-CoV-2. MAIN MEASURE: SARS-CoV-2 testing results and symptom report among employees and residents. KEY RESULTS: Eleven of the 16 SNFs had one or more resident or employee test positive. Overall, 46 (2.9%) employees had positive or inconclusive testing for SARS-CoV-2, and among those who completed surveys, most were asymptomatic and involved in direct patient care. The majority of employees tested were female (934, 73%), and most employees were Asian (392, 30%), Black (360, 28%), or white (360, 28%). Among the 1208 residents tested, 110 (9.1%) had positive or inconclusive results. There was no association between the presence of positive residents and positive employees within a SNF (p = 0.62, McNemar's test). CONCLUSIONS: In the largest study of SNFs to date, SARS-CoV-2 infections were detected among both employees and residents. Employees testing positive were often asymptomatic and involved in direct patient care. Surveillance testing is needed for SNF employees and residents during the pandemic response.

Distinct Early Serological Signatures Track with SARS-CoV-2 Survival.

As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.

Respiratory viral coinfection in a birth cohort of infants in rural Nepal.

BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the impacts of coinfection on disease severity are less understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in Nepal. Prospective weekly household-based active surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT-PCR. Coinfection was defined as the presence of two or more respiratory viruses detected as part of the same illness episode. RESULTS: Of 1730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected in their primary illness episode. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. The cohort of infants with coinfection had increased occurrence of fever lasting ≥ 4 days (OR 1.4, 95% CI: 1.1, 2.0), and so did the subset of coinfected infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 0.96, 1.6). CONCLUSION: A high proportion of infants had multiple viruses detected. Coinfection was associated with greater odds of fever lasting for four or more days, but not with increased illness severity by other measures.