Introduction: COVID-19 surveillance in congregate settings is important to mitigating disease, but the health and economic impact of testing remains unclear. Methods: The authors developed a Markov model to project the cost-utility of COVID-19 testing strategies in homeless shelters from the healthcare payer and societal perspective over 1 year. Model inputs utilized data from residents aged ≥18 years across 23 Seattle shelters from January 1, 2020, to May 31, 2021. No in-shelter surveillance was compared with scenarios of 2 COVID-19 testing strategies implemented monthly: polymerase chain reaction (PCR) testing and rapid antigen testing; scenarios in which only PCR testing was available were also evaluated. The primary health outcome was quality-adjusted life years. Interventions were considered cost-effective if the incremental cost-effectiveness ratio was ≤$150,000 per quality-adjusted life year and dominant if they saved costs and provided health effects. Results: When assuming the availability of both antigen and PCR tests, most rapid antigen testing strategies were cost-effective, whereas PCR testing was dominated by antigen testing. Compared with no in-shelter surveillance, antigen testing increased mean quality-adjusted life years by 0.0009 (0.03% infections averted) at an incremental cost of $97/resident from the healthcare perspective (incremental cost-effectiveness ratio=$112,352/quality-adjusted life year gained) and $8/resident from the societal perspective (incremental cost-effectiveness ratio=$9,627/quality-adjusted life year gained) at 75% vaccination coverage. PCR testing was not cost-effective when antigen testing was available but was cost-effective compared with no surveillance at low vaccination coverage levels (<30% coverage from the healthcare perspective and ≤48% coverage from the societal perspective). Probabilistic sensitivity analysis showed that antigen testing was cost-effective in 62% and 86% of simulations from the healthcare and societal perspectives, respectively. Conclusions: Modeled findings show that COVID-19 testing in shelters can be a cost-effective pandemic response. Antigen testing remained cost-effective at high vaccination levels, whereas PCR testing was most effective at low vaccination levels if antigen testing was not available. © 2024 The Author(s)

Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination.

Congregate homeless shelters are disproportionately affected by infectious disease outbreaks. We describe enterovirus epidemiology across 23 adult and family shelters in King County, Washington, USA, during October 2019-May 2021, by using repeated cross-sectional respiratory illness and environmental surveillance and viral genome sequencing. Among 3,281 participants >3 months of age, we identified coxsackievirus A21 (CVA21) in 39 adult residents (3.0% [95% CI 1.9%-4.8%] detection) across 7 shelters during October 2019-February 2020. We identified enterovirus D68 (EV-D68) in 5 adult residents in 2 shelters during October-November 2019. Of 812 environmental samples, 1 was EV-D68-positive and 5 were CVA21-positive. Other enteroviruses detected among residents, but not in environmental samples, included coxsackievirus A6/A4 in 3 children. No enteroviruses were detected during April 2020-May 2021. Phylogenetically clustered CVA21 and EV-D68 cases occurred in some shelters. Some shelters also hosted multiple CVA21 lineages.

Introduction: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time. Methods: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors. Results: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre–COVID-19 vaccine, ARI-related school (56% vs 10%, p<0.001) absenteeism decreased and masking increased (3% vs 28%, p<0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p<0.001), avoiding contact with non-household members (26% vs 58%, p<0.001), and staying home (37% vs 69%, p<0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36). Conclusions: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions. © 2024 The Authors

BACKGROUND: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases. METHODS: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days. RESULTS: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household. CONCLUSIONS: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2. TRIAL REGISTRATION IDENTIFIER: NCT04141930, Date of registration 28/10/2019.

BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: We retrospectively analyzed data from a longitudinal household cohort study from October 2019-June 2021. Enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swabs; after April 2020, participants with ARI or laboratory-confirmed SARS-CoV-2 and their household members self-collected nasal swabs. Specimens were tested via multiplex RT-PCR for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (n=406, 9.5%). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8, 14.8%) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days following primary detection; risk varied by primary virus: parainfluenza, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, | 34 SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or | 35 outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 | 36 homeless shelters in King County, Washington to estimate the occurrence of laboratory37 confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys | 38 and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 | 39 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified | 40 4.74 (95% CI 4.00 – 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI | 41 4.12 – 5.91; staff: 3.86, 95% CI 2.43 – 5.79). Most infections were asymptomatic at time of | 42 detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher | 43 test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, | 44 residents were less likely to report symptoms than staff. Participants who were vaccinated | 45 against seasonal influenza and were current smokers had lower odds of having an infection | 46 detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in | 47 ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate | 48 settings.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged >=3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00 - 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12 - 5.91; staff: 3.86, 95% CI 2.43 - 5.79). Most infections were asymptomatic at time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

BACKGROUND: Respiratory viruses might influence Streptococcus pneumoniae nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative S. pneumoniae nasal carriage density in a household setting before and during the COVID-19 pandemic. METHODS: From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including S. pneumoniae, rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative S. pneumoniae nasal carriage density, estimated by the inverse of S. pneumoniae relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of S. pneumoniae Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households. RESULTS: We collected 346 swabs from 239 individuals in 151 households that tested positive for S. pneumoniae (n = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative S. pneumoniae nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus (P < 0.01 for each). When stratified by age, semiquantitative S. pneumoniae nasal carriage density was significantly greater with viral co-detection among children aged <5 (P = 0.002) and 5-17 years (P = 0.005), but not among adults aged 18-64 years (P = 0.29). CONCLUSION: Detection of common respiratory viruses was associated with greater concurrent S. pneumoniae semiquantitative nasal carriage density in a household setting among children, but not adults.

PURPOSE: The study purpose was to learn and describe 1) where homeless shelter residents receive health care, 2) what contributes to positive or negative health care experiences among shelter residents, and 3) shelter resident perceptions toward health care. METHODS: Semi-structured interviews (SSIs) utilizing purposive sampling and focus group discussions (FGDs) utilizing convenience sampling were conducted at 6 homeless shelters in Seattle-King County, Washington, during July-October 2021. All residents (age ≥18) were eligible to participate. SSIs were conducted with 25 residents, and 8 FGDs were held. Thematic analysis was conducted using Dedoose. RESULTS: Participants received health care in settings ranging from no regular care to primary care providers. Four elements emerged as contributing positively and negatively to health care experiences: 1) ability to access health care financially, physically, and technologically; 2) clarity of communication from providers and staff about appointment logistics, diagnoses, and treatment options; 3) ease of securing timely follow-up services; and 4) respect versus stigma and discrimination from providers and staff. Participants who felt positively toward health care found low- or no-cost care to be widely available and encouraged others to seek care. However, some participants described health care in the United States as greedy, classist, discriminatory, and untrustworthy. Participants reported delaying care and self-medicating in anticipation of discrimination. CONCLUSIONS: Findings demonstrate that while people experiencing homelessness can have positive experiences with health care, many have faced negative interactions with health systems. Improving the patient experience for those experiencing homelessness can increase engagement and improve health outcomes.

Respiratory syncytial virus (RSV) causes disproportionate morbidity and mortality in vulnerable populations. We tested residents of homeless shelters in Seattle, Washington for RSV in a repeated cross-sectional study as part of community surveillance for respiratory viruses. Of 15 364 specimens tested, 35 had RSV detected, compared to 77 with influenza. The most common symptoms for both RSV and influenza were cough and rhinorrhea. Many individuals with RSV (39%) and influenza (58%) reported that their illness significantly impacted their ability to perform their regular activities. RSV and influenza demonstrated similar clinical presentations and burden of illness in vulnerable populations living in congregate settings.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

INTRODUCTION: Achieving high COVID-19 vaccination coverage in homeless shelters is critical in preventing morbidity, mortality, and outbreaks, however, vaccination coverage remains lower among people experiencing homelessness (PEH) than the general population. METHODS: We conducted a cross-sectional study to retrospectively describe attitudes and identify factors associated with change in COVID-19 vaccination intent among shelter residents and staff during March 2020 - August 2021. To identify factors associated with change in COVID-19 vaccine intent becoming more positive overall compared to other attitudes, we utilized a Poisson model to calculate Risk Ratios with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. RESULTS: From July 12 - August 2, 2021, 97 residents and 20 staff participated in surveys across six shelters in Seattle King County, Washington. Intent to be vaccinated against COVID-19 increased from 45.3% (n=53) when recalling attitudes in March 2020 to 74.4% (n=87) as of August 2021, and was similar among residents and staff. Many participants (43.6%, n=51) indicated feeling increasingly accepting about receiving a COVID-19 vaccine since March 2020, while 13.7% (n=16) changed back and forth, 10.3% (n=12) became more hesitant, and 32.5% (n=38) had no change in intent. In the model examining the relationship between becoming more positive about receiving a COVID-19 vaccine compared to all other attitudes (n=116), we found a 57.2% increase in vaccine acceptability (RR 1.57; 95% CI: 1.01, 2.45) among those who reported worsening mental health since the start of the pandemic. CONCLUSIONS: Findings highlight opportunities to improve communication with residents and staff about COVID-19 vaccination and support a need for continued dialogue and a person-centered approach to understanding the sociocultural complexities and dynamism of vaccine attitudes at shelters.Clinical Trial Registry Number: NCT04141917.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused substantial global morbidity and deaths, leading governments to turn to non-pharmaceutical interventions to slow down the spread of infection and lessen the burden on health care systems. These policies have evolved over the course of the COVID-19 pandemic, including after the availability of COVID-19 vaccines, with regional and country-level differences in their ongoing use. The COVID-19 pandemic has been associated with changes in respiratory virus infections worldwide, which have differed between virus types. Reductions in respiratory virus infections, including by influenza virus and respiratory syncytial virus, were most notable at the onset of the COVID-19 pandemic and continued in varying degrees through subsequent waves of SARS-CoV-2 infections. The decreases in community infection burden have resulted in reduced hospitalizations and deaths associated with non-SARS-CoV-2 respiratory infections. Respiratory virus evolution relies on the maintaining of a diverse genetic pool, but evidence of genetic bottlenecking brought on by case reduction during the COVID-19 pandemic has resulted in reduced genetic diversity of some respiratory viruses, including influenza virus. By describing the differences in these changes between viral species across different geographies over the course of the COVID-19 pandemic, we may better understand the complex factors involved in community co-circulation of respiratory viruses.

We implemented a voluntary SARS-CoV-2 screening testing study for kindergarten-2nd grade students in a Washington School district. Weekly SARS-CoV-2 testing participation was higher for students with staff-collected nasal swabs at school than for students with parent-collected swabs at home.

BACKGROUND: The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings. METHODS: We analysed data from a clinical trial and SARS-CoV-2 surveillance study at 23 homeless shelter sites in King County, Washington between October 2019-May 2021. Eligible participants were shelter residents aged 3 months with acute respiratory illness. We collected enrolment data and nasal samples for respiratory virus testing using multiplex RT-PCR platform including HCoV. Beginning April 1, 2020, eligibility expanded to shelter residents and staff regardless of symptoms. HCoV species was determined by RT-PCR with species-specific primers, OpenArray assay or genomic sequencing for samples with an OpenArray relative cycle threshold <22. FINDINGS: Of the 14,464 samples from 3281 participants between October 2019-May 2021, 107 were positive for HCoV from 90 participants (median age 40 years, range: 09-81 years, 38% female). HCoV-HKU1 was the most common species identified before and after community-wide mitigation. No HCoV-positive samples were identified between May 2020-December 2020. Adults aged 50 years had the highest detection of HCoV (11%) among virus-positive samples among all age-groups. Species and sequence data showed diversity between and within HCoV species over the study period. INTERPRETATION: HCoV infections occurred in all congregate homeless shelter site age-groups with the greatest proportion among those aged 50 years. Species and sequencing data highlight the complexity of HCoV epidemiology within and between shelters sites. FUNDING: Gates Ventures, Centers for Disease Control and Prevention, National Institute of Health.

BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged 3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After April 1, 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1,066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the COVID-19 pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for 4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and was most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic.

INTRODUCTION: Little is known about COVID-19 vaccination intent among people experiencing homelessness. This study assesses surveyed COVID-19 vaccination intent among adult homeless shelter residents and staff and identifies factors associated with vaccine deliberation (responded "undecided") and reluctance (responded "no"), including time trends. METHODS: From 11/1/2020-2/28/21, we conducted repeated cross-sectional surveys at nine shelters in King County, WA as part of ongoing community-based SARS-CoV-2 surveillance. We used a multinomial model to identify characteristics associated with vaccine deliberation and reluctance. RESULTS: A total of 969 unique staff (n = 297) and residents (n = 672) participated and provided 3966 survey responses. Among residents, 53.7% (n = 361) were vaccine accepting, 28.1% reluctant, 17.6% deliberative, and 0.6% already vaccinated, whereas among staff 56.2% were vaccine accepting, 14.1% were reluctant, 16.5% were deliberative, and 13.1% already vaccinated at their last survey. We observed higher odds of vaccine deliberation or reluctance among Black/African American individuals, those who did not receive a seasonal influenza vaccine, and those with lower educational attainment. There was no significant trend towards vaccine acceptance. CONCLUSIONS: Strong disparities in vaccine intent based on race, education, and prior vaccine history were observed. Increased vaccine intent over the study period was not detected. An intersectional, person-centered approach to addressing health inequities by public health authorities planning vaccination campaigns in shelters is recommended. Clinical Trial Registry Number: NCT04141917.

Influenza vaccination and antiviral therapeutics may attenuate disease, decreasing severity of illness in vaccinated and treated persons. Standardized assessment tools, definitions of disease severity, and clinical endpoints would support characterizing the attenuating effects of influenza vaccines and antivirals. We review potential clinical parameters and endpoints that may be useful for ordinal scales evaluating attenuating effects of influenza vaccines and antivirals in hospital-based studies. In studies of influenza and community-acquired pneumonia, common physiologic parameters that predicted outcomes such as mortality, ICU admission, complications, and duration of stay included vital signs (hypotension, tachypnea, fever, hypoxia), laboratory results (blood urea nitrogen, platelets, serum sodium), and radiographic findings of infiltrates or effusions. Ordinal scales based on these parameters may be useful endpoints for evaluating attenuating effects of influenza vaccines and therapeutics. Factors such as clinical and policy relevance, reproducibility, and specificity of measurements should be considered when creating a standardized ordinal scale for assessment.

BACKGROUND: Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. METHODS: We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons. RESULTS: We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). CONCLUSION: We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

Seasonal influenza epidemics result in substantial health care burden annually. Early initiation of antiviral treatment of influenza has been shown to reduce the risk of complications and duration of illness. Pregnant and postpartum women may be at increased risk for influenza-associated complications; however, pregnant women have been generally excluded from clinical trials of antiviral treatment of influenza. In this review, we summarize the available evidence on the clinical effectiveness and safety of antiviral treatment of pregnant women with influenza. Observational data show a reduction of severe outcomes when pregnant and postpartum women are treated with oseltamivir and other neuraminidase inhibitors without increased risk of adverse maternal, fetal, or neonatal outcomes. Due to lack of safety and efficacy data for baloxavir treatment of pregnant and postpartum women, baloxavir is currently not recommended for use in these populations.

IMPORTANCE: The association between COVID-19 symptoms and SARS-CoV-2 viral levels in children living in the community is not well understood. OBJECTIVE: To characterize symptoms of pediatric COVID-19 in the community and analyze the association between symptoms and SARS-CoV-2 RNA levels, as approximated by cycle threshold (Ct) values, in children and adults. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a respiratory virus surveillance platform in persons of all ages to detect community COVID-19 cases from March 23 to November 9, 2020. A population-based convenience sample of children younger than 18 years and adults in King County, Washington, who enrolled online for home self-collection of upper respiratory samples for SARS-CoV-2 testing were included. EXPOSURES: Detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) from participant-collected samples. MAIN OUTCOMES AND MEASURES: RT-PCR-confirmed SARS-CoV-2 infection, with Ct values stratified by age and symptoms. RESULTS: Among 555 SARS-CoV-2-positive participants (mean [SD] age, 33.7 [20.1] years; 320 were female [57.7%]), 47 of 123 children (38.2%) were asymptomatic compared with 31 of 432 adults (7.2%). When symptomatic, fewer symptoms were reported in children compared with adults (mean [SD], 1.6 [2.0] vs 4.5 [3.1]). Symptomatic individuals had lower Ct values (which corresponded to higher viral RNA levels) than asymptomatic individuals (adjusted estimate for children, -3.0; 95% CI, -5.5 to -0.6; P = .02; adjusted estimate for adults, -2.9; 95% CI, -5.2 to -0.6; P = .01). The difference in mean Ct values was neither statistically significant between symptomatic children and symptomatic adults (adjusted estimate, -0.7; 95% CI, -2.2 to 0.9; P = .41) nor between asymptomatic children and asymptomatic adults (adjusted estimate, -0.6; 95% CI, -4.0 to 2.8; P = .74). CONCLUSIONS AND RELEVANCE: In this community-based cross-sectional study, SARS-CoV-2 RNA levels, as determined by Ct values, were significantly higher in symptomatic individuals than in asymptomatic individuals and no significant age-related differences were found. Further research is needed to understand the role of SARS-CoV-2 RNA levels and viral transmission.

IN RESPONSE: We thank Drs. Newton and Yeh and Dr. Schattner for emphasizing the need to further understand the relationship between influenza virus infection and acute cardiovascular events. In our analysis based on ICD codes, 4412 patients hospitalized with laboratory-confirmed influenza had acute IHD. Among these, 4.6% had ST-segment elevation MI, 43.6% had non–ST-segment elevation MI, 12% had acute MI without specification of the presence of ST-segment elevation, and 38.4% had other acute IHD not otherwise specified; only 1.4% of patients had unstable angina as the only evidence of acute IHD. For patients with MI, we were unable to further differentiate between type I or II MI because of limitations of the ICD coding system. As for in-hospital outcomes among those with MI, patients in all 3 categories had a similar length of stay (median of 5 days). However, those with ST-segment elevation predictably had the highest percentage of intensive care unit admissions (59.7%), mechanical ventilatory support (32.6%), and in-hospital mortality (26.7%).

BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.

BACKGROUND: Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics. OBJECTIVE: To examine acute cardiovascular events and determine risk factors for acute heart failure (aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza. DESIGN: Cross-sectional study. SETTING: U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons. PARTICIPANTS: Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner. MEASUREMENTS: Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD. RESULTS: Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years [interquartile range, 54 to 81 years]) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza. LIMITATION: Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias. CONCLUSION: In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

OBJECTIVE: To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to SARS-CoV-2, by conducting a systematic analysis of studies from different settings which used various inclusion criteria. STUDY DESIGN: MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020 through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. RESULTS: Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: three studies selected patients diagnosed with Kawasaki disease (KD), two required cardiovascular involvement, and three had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for SARS-CoV-2 RT-PCR tests ranged from 13 to 69% and for serology, from 75 to 100%. MIS-C patients had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. CONCLUSIONS: This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

BACKGROUND: Preventing severe complications of influenza such as hospitalization is a public health priority; however, estimates of influenza vaccine effectiveness (VE) against influenza-associated acute lower respiratory tract infection (LRTI) hospitalizations are limited. We examined influenza VE against influenza-associated LRTIs in hospitalized adult patients. METHODS: We retrospectively analyzed data from a randomized trial of oseltamivir treatment in adults hospitalized with LRTI in Louisville, Kentucky, from 2010 to 2013. Patients were systematically tested for influenza at the time of enrollment. We estimated VE as 1 - the adjusted odds ratio (aOR) of antecedent vaccination in influenza-positives vs negatives × 100%. Vaccination status was obtained by patient self-report. Using logistic regression adjusting for age, sex, season, timing of illness, history of chronic lung disease, and activities of daily living, we estimated VE against hospitalized influenza-associated LRTIs and community-acquired pneumonia (CAP) with radiographic findings of infiltrate. RESULTS: Of 810 patients with LRTI (median age, 62 years), 184 (23%) were influenza-positive and 57% had radiographically confirmed CAP. Among influenza-positives and -negatives, respectively, 61% and 69% were vaccinated. Overall, 29% were hospitalized in the prior 90 days and >80% had comorbidities. Influenza-negatives were more likely to have a history of chronic obstructive pulmonary disease than influenza-positives (59% vs 48%; P = .01), but baseline medical conditions were otherwise similar. Overall, VE was 35% (95% CI, 4% to 56%) against influenza-associated LRTI and 51% (95% CI, 13% to 72%) against influenza-associated radiographically confirmed CAP. CONCLUSIONS: Vaccination reduced the risk of hospitalization for influenza-associated LRTI and radiographically confirmed CAP. Clinicians should maintain high rates of influenza vaccination to prevent severe influenza-associated complications.

BACKGROUND: A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome. METHODS: Hospitals in New York State reported cases of Kawasaki's disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020. RESULTS: As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days. CONCLUSIONS: The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.

This study assessed the spectrum of initial symptoms at the onset of polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) among health care personnel in King County, Washington.