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Among 133 cancer outpatients diagnosed with influenza between 2016 and 2018, 110 (83%) were prescribed oseltamivir. Among 109 with a known symptom onset date, 53% presented for care and 31% were prescribed oseltamivir within 48 hours. Patient/provider education and rapid diagnostics are needed to improve early oseltamivir use among cancer patients with influenza.

Background The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse-transcription PCR (RT–qPCR). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce. To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. Methods We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT–qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral inactivation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. Results After optimization, SwabExpress has a low limit of detection at 2–4 molecules/µL, 100% sensitivity, and 99.4% specificity when compared side by side with a traditional RT–qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. Conclusion SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

Background A constellation of debilitating symptoms, known as post-acute sequelae of COVID-19 (PASC), has been described in those in those with prior SARS-CoV-2 infection. While SARS-CoV-2 vaccination remains an effective way to prevent severe illness, PASC in individuals infected after vaccination is not well characterized. Methods A cohort of adults with laboratory confirmed SARS-CoV-2 infection were enrolled as cases and longitudinally followed between March 2020-March 2022 in the greater Seattle region. Demographic and acute illness surveys capturing baseline symptoms, infection severity and medical care were administered at enrollment (Table). Controls with no history of SARS-CoV-2 infection were concurrently followed. Symptom surveys were given at 6 months post-infection. Vaccination status was self-reported. We defined PASC as the presence of one or more symptoms that persisted for at least 4 weeks after acute SARS-CoV-2 infection. Table.Demographic and Illness Characteristics of Study Participants*Days since illness onset refers to the days passed since infection date. **Comorbidities included hypertension, diabetes mellitus, chronic obstructive pulmonary disease, cardiovascular disease, chronic liver disease, chronic kidney disease, HIV, current use of immunosuppressants or diagnosis of cancer. Results Of 369 cases and 93 controls 57% (median age 44.7 years; 59.3% female) and 30% (median age 50.0 years; 50.0% female), completed the 6-month survey, respectively (Table). A total of 174 cases were infected prior to vaccination and 35 were post-vaccination. A total of 58 (28%) cases reported symptoms at 6 months, compared to 5 (18%) controls (Figure). In participants infected pre-vaccination, 32% reported PASC symptoms, compared to 6% of those infected post-vaccination (Figure; P=0.001). Conclusion Our study found that the proportion of individuals reporting PASC at 6 months after infection was significantly higher among those infected before SARS-CoV-2 vaccination than those who were infected after. This suggests that timing of vaccination relative to SARS-CoV-2 infection may be associated with the development of PASC symptoms. Symptoms were still reported among many individuals with PASC who were vaccinated after their infection. Further research is required to understand the underlying mechanisms of PASC, and to characterize PASC in those infected after vaccination and with variant of concerns. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background The post-acute sequelae of COVID-19 (PASC) includes a constellation of debilitating symptoms after SARS-CoV-2 infection. Much remains unknown about the long-term health burden of COVID-19. We describe the symptom course and quality of life of adults up to 2 years after mild acute COVID-19. Methods Adults within 30 days of laboratory-confirmed acute COVID-19 were enrolled as cases from January – September 2020 and followed for 2 years. Demographic and symptom data were collected in an enrollment survey and at 6, 12 and 24 months post-infection. Surveys included vaccination status, symptom course, and quality of life assessments (Fatigue Assessment Scale (FAS) and EuroQual visual analog scale (VAS)). A cohort of SARS-CoV-2 uninfected controls was concurrently enrolled and surveyed. We used descriptive statistics to compare cases and controls and defined a p-value < 0.05 as significant. Results A total of 112 of 239 enrolled cases and 44 of 59 controls completed all surveys. Of the 112 cases, 105 (94%) had mild disease. In the 6, 12 and 24 month surveys, 39 (35%), 48 (43%) and 56 (50%) cases indicated at least one persistent symptom, respectively, compared to 4 (9%), 5 (11%) and 6 (14%) controls (Table 1). In all 3 surveys, fatigue and altered smell or taste were the most common post-infection symptoms among cases (Figure 1). At 2 years, 40 (36%) cases reported symptoms were improving or resolved and 30 (27%) reported symptoms continued to wax and wane. Symptoms improved and worsened for 10 and 4 cases, respectively, following a complete SARS-CoV-2 vaccination. 46% reported seeking medical attention for persistent symptoms and 34% of those employed reported symptoms negatively impacted their ability to work. When compared to controls in the 12 and 24 month surveys, cases had a significantly higher mean FAS score (p-value < 0.001 and 0.01, respectively) and significantly lower VAS score (p-value = 0.01 and < 0.001, respectively). Demographic and Clinical Characteristics of the Study Cohort a. Time since symptom onset in infected cohort and time since enrollment in healthy controls b. Other race/ethnicity included American Indian or Alaska Native, Black or African American, Native Hawaiian or other Pacific Islander, and more than 1 race. Percentage of participants reporting symptoms at 6-, 12-, and 24-months * Conclusion Symptoms associated with PASC were reported up to 2 years after infection with significant impacts on quality of life. These findings underscore the healthcare and societal burdens even after recovery from acute infection. As studies seek to identify the underlying mechanisms of PASC, prevention of acute infection remains the mainstay of COVID-19 burden mitigation. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Households represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under‐diagnosis and treatment delays. This study aimed to assess the feasibility of an at‐home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery. Methods We conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle‐area households with children during the 2019‐2020 influenza season using pre‐positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid‐nasal swabs and used a rapid home‐based influenza immunoassay. An additional home‐collected swab was returned to a laboratory for confirmatory influenza RT‐PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age‐eligible participants, following a telehealth encounter. Results 124 households comprising 481 individuals self‐monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which eight were true positives confirmed by RT‐PCR. The sensitivity and specificity of the home influenza test were 72.7% and 96.2%, respectively. There were eight home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription and all within 48 hours of symptom onset. Conclusions We demonstrate the feasibility of self‐testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.

Background Unusually high snowfall in western Washington State in February 2019 led to widespread school and workplace closures. We assessed the impact of social distancing caused by this extreme weather event on the transmission of respiratory viruses. Methods Residual specimens from patients evaluated for acute respiratory illness at hospitals in the Seattle metropolitan area were screened for a panel of respiratory viruses. Transmission models were fit to each virus to estimate the magnitude reduction in transmission due to weather-related disruptions. Changes in contact rates and care-seeking were informed by data on local traffic volumes and hospital visits. Results Disruption in contact patterns reduced effective contact rates during the intervention period by 16 to 95%, and cumulative disease incidence through the remainder of the season by 3 to 9%. Incidence reductions were greatest for viruses that were peaking when the disruption occurred and least for viruses in an early epidemic phase. Conclusion High-intensity, short-duration social distancing measures may substantially reduce total incidence in a respiratory virus epidemic if implemented near the epidemic peak. For SARS-CoV-2, this suggests that, even when SARS-CoV-2 spread is out of control, implementing short-term disruptions can prevent COVID-19 deaths.

BackgroundWashington State served as the initial epicenter of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in the United States. An understanding of the risk factors and clinical outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) may provide guidance for management.MethodsAll laboratory-confirmed COVID-19 cases in adults admitted to an academic medical center in Seattle, Washington, between 2 March and 26 March 2020 were included. We evaluated individuals with and without severe disease, defined as admission to the intensive care unit or death.ResultsOne hundred five COVID-19 patients were hospitalized. Thirty-five percent were admitted from a senior home or skilled nursing facility. The median age was 69 years, and half were women. Three or more comorbidities were present in 55% of patients, with hypertension (59%), obesity (47%), cardiovascular disease (38%), and diabetes (33%) being the most prevalent. Most (63%) had symptoms for ≥5 days prior to admission. Only 39% had fever in the first 24 hours, whereas 41% had hypoxia at admission. Seventy-three percent of patients had lymphopenia. Of 50 samples available for additional testing, no viral coinfections were identified. Severe disease occurred in 49%. Eighteen percent of patients were placed on mechanical ventilation, and the overall mortality rate was 33%.ConclusionsDuring the early days of the COVID-19 epidemic in Washington State, the disease had its greatest impact on elderly patients with medical comorbidities. We observed high rates of severe disease and mortality in our hospitalized patients.

Wide-scale assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies is critical to understanding population seroprevalence, correlates of protection, and the longevity of vaccine-elicited responses. Most SARS-CoV-2 studies characterize antibody responses in plasma/sera. While reliable and broadly used, these samples pose several logistical restrictions, such as requiring venipuncture for collection and a cold chain for transportation and storage. Dried blood spots (DBS) overcome these barriers as they can be self-collected by fingerstick and mailed and stored at ambient temperature. Here, we evaluate the suitability of DBS for SARS-CoV-2 antibody assays by comparing several antibody responses between paired plasma and DBS from SARS-CoV-2 convalescent and vaccinated individuals. We found that DBS not only reflected plasma antibody binding by enzyme-linked immunosorbent assay (ELISA) and epitope profiles using phage display, but also yielded SARS-CoV-2 neutralization titers that highly correlated with paired plasma. Neutralization measurement was further streamlined by adapting assays to a high-throughput 384-well format. This study supports the adoption of DBS for numerous SARS-CoV-2 binding and neutralization assays. IMPORTANCE Plasma and sera isolated from venous blood represent conventional sample types used for the evaluation of SARS-CoV-2 antibody responses after infection or vaccination. However, collection of these samples is invasive and requires trained personnel and equipment for immediate processing. Once collected, plasma and sera must be stored and shipped at cold temperatures. To define the risk of emerging SARS-CoV-2 variants and the longevity of immune responses to natural infection and vaccination, it will be necessary to measure various antibody features in populations around the world, including in resource-limited areas. A sampling method that is compatible with these settings and is suitable for a variety of SARS-CoV-2 antibody assays is therefore needed to continue to understand and curb the COVID-19 pandemic.

Background : While a growing body of literature describes antibody dynamics in serum, little is known about breast milk antibody titers in the months following SARS-CoV-2 infection. Objectives : We evaluated the dynamics of the humoral immune response to SARS-CoV-2 in two women who were breastfeeding when infected. We assessed paired breast milk and serum samples for six months post-infection for antibodies specific to the SARS-CoV-2 receptor binding domain (RBD) of the spike protein. Results : Starting at 10 days after symptom onset, IgA antibody levels were persistent over a 6-month time period in human milk. For both mothers, no detectable IgA was found in the samples collected pre-symptom onset. RBD-specific IgG and IgM antibodies in tandem serum collected from the two donors demonstrated stable IgG levels over the six-month time period post-symptom onset. Conclusions : We found that breastfeeding mothers produced a durable IgA response for up to six months following COVID-19 infection, suggesting an important role for breast milk in protection of infants.

BackgroundThe first US case of SARS-CoV-2 infection was detected on January 20, 2020. However, some serology studies suggest SARS-CoV-2 may have been present in the United States prior to that, as early as December 2019. The extent of domestic COVID-19 detection prior to 2020 has not been well-characterized.ObjectivesTo estimate the prevalence of SARS-CoV-2 antibody among healthcare users in the greater Seattle, Washington area from October 2019 through early April 2020.Study designWe tested residual samples from 766 Seattle-area adults for SARS-CoV-2 antibodies utilizing an ELISA against prefusion-stabilized Spike (S) protein.ResultsNo antibody-positive samples were found between October 2, 2019 and March 13, 2020. Prevalence rose to 1.2% in late March and early April 2020.ConclusionsThe absence of SARS-CoV-2 antibody-positive samples in October 2019 through mid-March, 2020, provides evidence against widespread circulation of COVID-19 among healthcare users in the Seattle area during that time. A small proportion of this metropolitan-area cohort had been infected with SARS-CoV-2 by spring of 2020.

BackgroundHouseholds represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under-diagnosis and treatment delays. This study aimed to assess the feasibility of an at-home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery.MethodsWe conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle-area households with children during the 2019-2020 influenza season using pre-positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid-nasal swabs and used a rapid home-based influenza immunoassay. An additional home-collected swab was returned to a laboratory for confirmatory influenza RT-PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age-eligible participants, following a telehealth encounter.Results124 households comprising 481 individuals self-monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which 8 were true positives confirmed by RT-PCR. The sensitivity and specificity of the home influenza test was 72.7% and 96.2%, respectively. There were 8 home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription, and all within 48 hours of symptom onset.ConclusionsWe demonstrate the feasibility of self-testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.SummaryIn this pilot study, 481 individuals self-monitored for respiratory symptoms. Of 58 home tests, 12 were influenza-positive. There were 8 baloxavir home deliveries within 48 hours of illness onset. A home-based approach to influenza diagnosis and treatment could be feasible.

While influenza and other respiratory pathogens cause significant morbidity and mortality, the community-based burden of these infections remains incompletely understood. The development of novel methods to detect respiratory infections is essential for mitigating epidemics and developing pandemic-preparedness infrastructure., While influenza and other respiratory pathogens cause significant morbidity and mortality, the community-based burden of these infections remains incompletely understood. The development of novel methods to detect respiratory infections is essential for mitigating epidemics and developing pandemic-preparedness infrastructure. From October 2019 to March 2020, we conducted a home-based cross-sectional study in the greater Seattle, WA, area, utilizing electronic consent and data collection instruments. Participants received nasal swab collection kits via rapid delivery within 24 hours of self-reporting respiratory symptoms. Samples were returned to the laboratory and were screened for 26 respiratory pathogens and a housekeeping gene. Participant data were recorded via online survey at the time of sample collection and 1 week later. Of the 4,572 consented participants, 4,359 (95.3%) received a home swab kit and 3,648 (83.7%) returned a nasal specimen for respiratory pathogen screening. The 3,638 testable samples had a mean RNase P relative cycle threshold (Crt) value of 19.0 (SD, 3.4), and 1,232 (33.9%) samples had positive results for one or more pathogens, including 645 (17.7%) influenza-positive specimens. Among the testable samples, the median time between shipment of the home swab kit and completion of laboratory testing was 8.0 days (interquartile range [IQR], 7.0 to 14.0). A single adverse event occurred and did not cause long-term effects or require medical attention. Home-based surveillance using online participant enrollment and specimen self-collection is a safe and feasible method for community-level monitoring of influenza and other respiratory pathogens, which can readily be adapted for use during pandemics.

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.

Profiling coronaviruses Among the coronaviruses that infect humans, four cause mild common colds, whereas three others, including the currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), result in severe infections. Shrock et al. used a technology known as VirScan to probe the antibody repertoires of hundreds of coronavirus disease 2019 (COVID-19) patients and pre–COVID-19 era controls. They identified hundreds of antibody targets, including several antibody epitopes shared by the mild and severe coronaviruses and many specific to SARS-CoV-2. A machine-learning model accurately classified patients infected with SARS-CoV-2 and guided the design of an assay for rapid SARS-CoV-2 antibody detection. The study also looked at how the antibody response and viral exposure history differ in patients with diverging outcomes, which could inform the production of improved vaccine and antibody therapies. Science , this issue p. eabd4250

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.

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 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.

Detection of Covid-19 through a Citywide Surveillance Platform The Seattle Flu study, initiated in 2018, mailed kits for home collection of midnasal swabs to people reporting respiratory symptoms. ...

Summary 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. While 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 on a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. While 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 S-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., Graphical Abstract, Highlights • Limited early differences across groups were observed in titers and neutralization • Five antibody features collectively could differentiate convalescents and deceased • A shift in the balance of spike versus nucleocapsid immunity separated the groups • Spike-specific phagocytic and complement fixing activity was enriched in convalescents, Although most SARS-CoV-2 infected individuals experience mild disease, a significant fraction of individuals become severely infected. Early biomarkers that predict outcome are urgently needed. Atyeo et al demonstrate that distinct acute SARS-CoV-2 humoral immune responses exist across severely ill individuals that ultimately convalesce or pass away.

Structured AbstractBackgroundThe urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse transcription PCR (RT-qPCR) (1). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce (2). To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction.MethodsWe evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral activation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance.ResultsAfter optimization, SwabExpress has a low limit of detection at 2-4 molecules/uL, 100% sensitivity, and 99.4% specificity when compared side-by-side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time.ConclusionSwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

IntroductionWhile seasonal influenza and other respiratory pathogens cause significant morbidity and mortality each year, the community-based burden of these infections remains incompletely understood. Understanding the prevalence, epidemiology, and transmission dynamics of respiratory pathogen infections among community-dwelling individuals is essential during pandemic and epidemic settings and for developing pandemic-preparedness infrastructure.Methods and AnalysisWe present the protocol for a novel, city-wide home-based cross-sectional study in the Seattle Metropolitan area, utilizing rapid delivery systems for self-collection of a nasal swab and return to the laboratory for respiratory pathogen testing. All participation takes place electronically, including recruitment, consent, and data collection. Within 48 hours of participants self-reporting respiratory symptoms, a nasal swab kit is delivered to the household via a courier service. Demographic and illness characteristics are collected at the time of sample collection and recovery and behavioral information collected one week later. Specimens are tested in the laboratory for multiple respiratory pathogens, and results are available on a public website for participants.Ethics and DisseminationThe study was approved by the University of Washington Institutional Review Board (Protocol #00006181). Results will be disseminated through peer-reviewed publications, talks at conferences, and on the Study Website (www.seattleflu.org).Article SummaryThe findings of this study will inform whether a home-based approach to city-wide respiratory surveillance is possible in epidemic settingsA key strength of this study is that it is conducted across diverse neighborhoods spanning a major metropolitan areaClinical findings may not be generalizable, as they are reliant on self-report (vaccination status, symptoms, healthcare utilization, etc.)

BACKGROUNDUnusually high snowfall in western Washington State in February 2019 led to widespread school and workplace closures. We assessed the impact of social distancing caused by this extreme weather event on the transmission of respiratory viruses.METHODSResidual specimens from patients evaluated for acute respiratory illness at hospitals in the Seattle metropolitan area were screened for a panel of respiratory viruses. Transmission models were fit to each virus, with disruption of contact rates and care-seeking informed by data on local traffic volumes and hospital admissions.RESULTSDisruption in contact patterns reduced effective contact rates during the intervention period by 16% to 95%, and cumulative disease incidence through the remainder of the season by 3% to 9%. Incidence reductions were greatest for viruses that were peaking when the disruption occurred and least for viruses in early epidemic phase.CONCLUSIONHigh-intensity, short-duration social distancing measures may substantially reduce total incidence in a respiratory virus epidemic if implemented near the epidemic peak.One sentence summaryDisruptions of school and work due to heavy snowfall in the Seattle metro area reduced the total size of respiratory virus epidemics by up to 9%.

Patients with chronic granulomatous disease are at increased risk for invasive aspergillosis. Cryptic Aspergillus species are being increasingly recognized as distinct causes of infection in this population. In this study, we describe the first case of Aspergillus udagawae vertebral osteomyelitis in a patient with X-linked chronic granulomatous disease.

Many individuals experience persistent symptoms and a decline in health-related quality of life (HRQoL) after coronavirus disease 2019 (COVID-19) illness.1 Existing studies have focused on hospitalized individuals 30 to 90 days after illness onset2,3,4 and have reported symptoms up to 110 days after illness.3 Longer-term sequelae in outpatients have not been well characterized.

Increased diagnostics are urgently needed to contain the spread of coronavirus disease 2019 (COVID-19). Home self-collected swabs may increase testing access while minimizing exposure risk to health care workers and depletion of personal protective equipment, allowing for early community detection of COVID-19. A comparison of unsupervised home self-collected swabs with clinician-collected nasopharyngeal swabs for COVID-19 diagnosis has not been well described.

Introduction: The World Health Organization (WHO) recommends HIV Counseling and Testing (HCT) in a range of clinical settings. We describe the characteristics of patients diagnosed with HIV on the medical and surgical wards at a tertiary care hospital in Malawi. Methods: Under the universal opt-out HCT protocol we characterized the number of new HIV/AIDS infections and associated clinical features among hospitalized surgical and medical patients diagnosed during the course of admission. Results: All 2985 and 3959 medical and surgical patients, respectively, admitted between April 2012 and January 2013 were screened for HCT. 62% and 89% of medical and surgical patients, respectively, had an unknown status on admission and qualified for testing. Of the patients with an unknown status, a new HIV diagnosis was made in 20% and 7% of medical and surgical patients, respectively. Of the newly diagnosed patients with a CD4 count recorded, 91% and 67% of medical and surgical patients, respectively, had a count less than 350, qualifying for ART by Malawi ART guidelines. Newly HIV-diagnosed medical and surgical patients had an inpatient mortality of 20% and 2%, respectively. Discussion: While newly diagnosed HIV-positive medical patients had high inpatient mortality and higher rates of WHO stage 3 or 4 conditions, surgical patients presented with less advanced HIV, though still meeting ART initiation guidelines. The medical inpatient wards are an obvious choice for implementing voluntary counseling and testing (VCT), but surgical patients present with less advanced disease and starting treatment in this group could result in more years of life gained.

ObjectivesTo determine whether rhinovirus (RV) species is associated with more severe clinical illness in adults.MethodsSeventy-two RV-positive viral respiratory samples from adult patients were sequenced and analyzed phylogenetically after reverse transcriptase polymerase chain reaction of the region spanning the VP4 gene and 5′ terminus of the VP2 gene. The clinical features and severity of illness associated with the different RV species were compared.ResultsPhylogenetic analysis identified three distinct clusters as RV-A (54%), B (11%), or C (35%) species. In an unadjusted model, patients with RV-B infection were significantly more likely to have the composite outcome variable of death or intensive care unit admission (P = .03), but this effect diminished when controlling for patient sex. A logistic model of the relationship between RV species and adverse outcomes produced nonsignificant odds ratios when controlling for patient sex.ConclusionsInfection with RV-A or RV-B was associated with greater severity of illness in our adult population; however, the association disappeared after controlling for confounders.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies., By correlating patient symptoms with in-depth profiling of blood cells and plasma components throughout COVID-19 infection, this study identifies factors that may predict sustained disease.