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mRNA vaccination of individuals with prior SARS-CoV-2 infection provides superior protection against breakthrough infections with variants of concern compared with vaccination in the absence of prior infection. However, the immune mechanisms by which this hybrid immunity is generated and maintained are unknown. Whereas genetic variation in spike glycoprotein effectively subverts neutralizing Abs, spike-specific T cells are generally maintained against SARS-CoV-2 variants. Thus, we comprehensively profiled human T cell responses against the S1 and S2 domains of spike glycoprotein in a cohort of SARS-CoV-2–naive (n = 13) or –convalescent (n = 17) individuals who received two-dose mRNA vaccine series and were matched by age, sex, and vaccine type. Using flow cytometry, we observed that the overall functional breadth of CD4 T cells and polyfunctional Th1 responses was similar between the two groups. However, polyfunctional cytotoxic CD4 T cell responses against both S1 and S2 domains trended higher among convalescent subjects. Multimodal single-cell RNA sequencing revealed diverse functional programs in spike-specific CD4 and CD8 T cells in both groups. However, convalescent individuals displayed enhanced cytotoxic and antiviral CD8 T cell responses to both S1 and S2 in the absence of cytokine production. Taken together, our data suggest that cytotoxic CD4 and CD8 T cells targeting spike glycoprotein may partially account for hybrid immunity and protection against breakthrough infections with SARS-CoV-2.

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.

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.

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 older 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.

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 1 April 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 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (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 were 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. Clinical Trials Registration NCT04141917.

Rapid molecular diagnostic tests have been critical in the response to the COVID-19 pandemic. It is important to evaluate the ability of these assays to identify variants of concern, particularly across varying collection and storage conditions. Nasal swabs positive for Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.167.2), Gamma (P.1), or Omicron (B.1.1.529) variants of concern (VOCs) were stored in TE buffer and viral transport media (VTM). We evaluated the sensitivity of the Cepheid Xpert® Xpress SARS-CoV-2 assay in detecting VOC samples and validated TE buffer for use with the assay. Testing of known VOC positives revealed no substantial reduction of PCR sensitivity. Comparison of TE and VTM samples also revealed no reduction in performance when using TE buffer, validating the use of TE buffer to store SARS-CoV-2 samples. SARS-CoV-2 VOCs collected and stored across various conditions can be detected by the Cepheid Xpert® Xpress SARS-CoV-2 assay.

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 3,966 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.

IntroductionAlthough SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged MethodsCASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays.AnalysisCox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households.Ethics and disseminationAll study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study.Strengths/LimitationsCASCADIA will include a large sample of children and adults that will contribute to estimation of vaccine effectiveness.The study will generate a data repository that can be used to address many research questions, such as duration of SARS-CoV-2 serologic results, post-acute sequelae of COVID-19, and re-infection rates.Retention and compliance may be challenging given the four-year duration of the study.Annual blood collection for assessment of humoral immunity may be a potential deterrent for participation, particularly among younger children.

Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited.We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents ≥3 months with cough or ≥2 acute respiratory illness (ARI) symptoms and onset7 days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was48 h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance.During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A = 14; B = 37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset 48 h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related.Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity.

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 pose 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 two days for fourteen days. Results: In total, 1,371 participants collected 2,029 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

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.Significance StatementSARS-CoV-2 infections can result in diverse clinical outcomes, including severe disease. Monoclonal antibodies (mAbs) have been used therapeutically to treat infection, but the emergence of variants has compromised their efficacy. Thus, identifying mAbs that are more durable in the face of SARS-CoV-2 evolution is a pressing need. Here, we describe four new mAbs isolated from a Delta-breakthrough infection, that can potently neutralize diverse variants, including multiple Omicron variants. In addition, one mAb shows broader activity against coronaviruses. The breadth of these mAbs is due to their focus on highly conserved regions of the viral protein antigen, including regions that are required for the virus to enter the cell. These properties make them promising candidates for therapeutic use.

ImportanceFew US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for cocirculating endemic viruses, such as rhinovirus.ObjectivesTo evaluate how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these with the risk factors associated with rhinovirus test positivity.Design, Setting, and ParticipantsThis case-control study used a test-negative design with multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 25-month period. The study was conducted among symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study in King County, Washington, from June 2020 to July 2022.ExposuresSelf-reported data for 15 demographic and health behavior variables and 16 symptoms.Main Outcomes and MeasuresReverse transcription–polymerase chain reaction–confirmed SARS-CoV-2 or rhinovirus infection.ResultsAnalyses included data from 23 498 individuals. The median (IQR) age of participants was 34.33 (22.42-45.08) years, 13 878 (59.06%) were female, 4018 (17.10%) identified as Asian, 654 (2.78%) identified as Black, and 2193 (9.33%) identified as Hispanic. Close contact with an individual with SARS-CoV-2 (adjusted odds ratio [aOR], 3.89; 95% CI, 3.34-4.57) and loss of smell or taste (aOR, 3.49; 95% CI, 2.77-4.41) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated individual with SARS-CoV-2 (aOR, 2.03; 95% CI, 1.56-2.79) was associated with lower odds of testing positive than contact with an unvaccinated individual with SARS-CoV-2 (aOR, 4.04; 95% CI, 2.39-7.23). Sore throat was associated with Omicron infection (aOR, 2.27; 95% CI, 1.68-3.20) but not Delta infection. Vaccine effectiveness for participants fully vaccinated with a booster dose was 93% (95% CI, 73%-100%) for Delta, but not significant for Omicron. Variables associated with rhinovirus test positivity included being younger than 12 years (aOR, 3.92; 95% CI, 3.42-4.51) and experiencing a runny or stuffy nose (aOR, 4.58; 95% CI, 4.07-5.21). Black race, residing in south King County, and households with 5 or more people were significantly associated with both SARS-CoV-2 and rhinovirus test positivity.Conclusions and RelevanceIn this case-control study of 23 498 symptomatic individuals, estimated risk factors and symptoms associated with SARS-CoV-2 infection changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and sociodemographic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection. Trends in testing behavior and availability may influence these results.

Background Families with children may be at higher risk for influenza infection. Community transmission can suffer from underreporting as testing is often not performed. We studied the epidemiology of influenza in households with school-aged children using home-based sample collection. Methods We conducted a remote household study surveilling respiratory viruses from November 2019-June 2021, in King County, Washington (WA), USA. Households with school-aged children were enrolled, mailed home specimen collection kits, and asked to self-assess for weekly acute respiratory illness (ARI) using remote survey platforms. Participants with ARI symptoms were prompted to complete serial illness surveys and self-collect/parent collect mid-turbinate nasal swabs. Samples were sent to a University of Washington study laboratory for RT-PCR influenza testing. Influenza rates were compared to WA Department of Health (DOH) reporting. Results A total of 1861 ARI events were reported among 992 adults and 869 children in 470 households; 75 influenza cases were detected (36 influenza A and 39 influenza B). The study participant median age was 32 years (0-84), 10 years (1-49) for influenza A, and 11 years (3-49) for influenza B cases. Overall 13% of households had an influenza case, of which 13 (22%) reported >1 case. A total of 81% of participants reported receipt of one dose of the 2019-2020 influenza vaccine, including 91% of influenza A and 90% of influenza B cases, and 84% received the 2020-2021 influenza vaccine. Like WA DOH, we observed a wave of influenza B cases followed by influenza A in 2019-2020. During influenza season 2020-2021, WA DOH reported 9 positive influenza tests and none observed in our study. Commonly, influenza case-patients reported were fever, cough, rhinorrhea, and fatigue. GI symptoms were more common in children than adults. Of the cases, 92% of influenza A and 78% of influenza B occurred in children. Figure 1.Influenza A and B cases from 2019-2021Figure 2A.Reported Symptoms of Influenza A D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 30 participants responded and of respondents, 13% D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 28 participants responded and of respondents, 4% Conclusion Influenza illness in 2019-2020 was initially influenza B, and subsequently replaced by influenza A. Most cases were in children and adolescents, despite at least one dose of influenza vaccine. Symptoms were widely distributed and similar between influenza A and B. Influenza incidence in our cohort declined to zero with the rise of SARS-CoV-2 cases and widespread mitigation efforts. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

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 COVID-19 vaccines are important to mitigate severe disease in congregate settings, yet uptake remains lower among people experiencing homelessness (PEH) than in the general population. This study aimed to explain changes in COVID-19 vaccination intent over time and identify modifiable factors to improve vaccine acceptance among PEH. Methods We utilized the Health Belief Model and 3Cs Model of Vaccine Hesitancy to develop a conceptual framework to explore factors that may influence COVID-19 vaccination intent among PEH. Between July 27 - October 15, 2021, we conducted semi-structured interviews (SSIs) and focus group discussions (FGDs) across six homeless shelters in Seattle-King County, Washington. Residents and staff aged 18 years and older were recruited through purposive sampling for SSIs and convenience sampling for FGDs. We captured retrospective information about perceptions of and intent to receive COVID-19 vaccines between March 2020 - August 2021. Thematic analysis was conducted using Dedoose. Results We conducted 31 SSIs (25 residents and six staff) and eight FGDs with 43 residents. Participants reported that too much contradictory and changing information about COVID-19 vaccines led to confusion. Information deemed trustworthy (i.e., objective, honest, professional, and recommended by others) contributed to individual’s knowledge and in some cases changed their vaccination intent. Despite intention to vaccinate, participants reported barriers to COVID-19 vaccine access including availability, eligibility, appointments, and timeliness. While many intended to get vaccinated on their own, others were motivated by incentives and requirements. Participants presented recommendations to improve COVID-19 information content and dissemination, access, and incentives in shelter settings (Table 1). Table 1.Recommendations for Interventions to Increase COVID-19 Vaccine Uptake in Shelter Settings Conclusion COVID-19 vaccination strategies that are rooted in the voices and experiences of PEH are presented and can inform improved vaccine implementation among key stakeholders. Future research should test recommended strategies to determine feasibility and effectiveness in shelter settings. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background The need for community surveillance of respiratory viruses in high-risk settings such as homeless shelters has been underscored by the COVID-19 pandemic. Here, we show that sampling high-touch surfaces is a low-cost, minimally intensive means of community respiratory virus surveillance. Methods Environmental samples were collected weekly from adult and family homeless shelters in King County, WA from November 2019 – April 2020. At times when residents were present, a 10cm2 area of selected high-touch surfaces were swabbed and bioaerosol samples were collected in high-traffic areas. Surfaces included entrance and restroom doorknobs, counters, and surfaces unique to each shelter. Study staff collected mid-turbinate swabs from shelter resident participants aged > 3 months with symptoms of acute respiratory illness (ARI). All samples were tested by RT-PCR for 27 viruses. From January 1, 2020 onward, samples were also tested for SARS-CoV-2. Results A total of 788 environmental swabs, 1509 nasal swabs, and 98 bioaerosol samples from 6 adult and 3 family shelters were tested. Adenovirus (109 positive swabs, 13.8% of tested swabs), rhinovirus (107, 13.6%) and human bocavirus (62, 7.9%) were the most frequently detected viruses in surface swabs. Rhinovirus (160, 10.6%), human coronaviruses (79, 5.24%) and influenza B (43, 2.85%) were the most detected in nasal swabs. All viruses detected in nasal swabs were found in surface swabs. Of 9 surfaces, exterior bathroom doorknobs were the physical location with the highest number of pathogens detected. SARS-CoV-2 was first detected in surface swabs on 3/20/20, and in nasal swabs on 3/10/20. Bioaerosol samples detected virus in a low percentage of samples relative to surface and nasal swabs. Table 1Count and period prevalence of environmental viral detection by shelter type, November 18, 2019 - April 10, 2020.Figure 1Number of viral pathogens detected from environmental swabs, disaggregated by shelter type.Figure 2Bar graphs comparing prevalence of respiratory pathogen detection in mid-turbinate nasal swabs and environmental swabs/bioaerosol samples by epidemiologic week, November 18, 2019 - April 30, 2020. Conclusion Respiratory viruses detected through environmental sampling in homeless shelters were similar to the viruses detected from ARI episodes in study participants. Environmental surface sampling presents a plausible, minimally invasive method of surveillance for both endemic and emerging respiratory pathogens, as evidenced by the detection of SARS-CoV-2 during the early stages of the pandemic. Further research could focus on sampling public locations for broader community surveillance and culturing viruses found on these surfaces. Disclosures Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Non-pharmaceutical interventions (NPIs), such as masking and social distancing, can reduce SARS-CoV-2 transmission. Longitudinal behavioral data in individuals with acute respiratory illness (ARI) during the COVID-19 pandemic are limited. We describe changes in adherence to NPIs and the impact of ARIs on work or school in families before and during the COVID-19 pandemic. Methods From November 2019 to June 2021, households with school-aged children in King County, WA, were remotely monitored on a weekly basis for symptoms of respiratory illness. Participants with ARI (cough or ≥2 qualifying symptoms) were asked about illness-related behavior changes (e.g. masking, isolation, hand hygiene, surface cleaning, public transit use) and impacts on school/work 7 days after initial symptom report. Using generalized estimating equations for household clusters, we compared the frequency of behavior changes and school/work impact during 3 time periods: the pre-/early COVID-19 pandemic period (11/14/19-3/22/20), pre-vaccine period (3/23/20-12/10/20), and post-COVID-19 vaccine period (12/11/20-6/19/21). Results Of 1861 participants in 470 households, 695 (37%, from 70% of households) reported 1157 ARIs. Over the 3 time periods, the percent of ill participants who reported staying home (34 vs 34 vs 54%, respectively, P< .001), avoiding contact with others (25 vs 28 vs 45%, P< .001), and masking (3 vs 23 vs 38%, P< .001) increased (Fig 1A). Other illness-related behaviors, including washing hands and disinfecting surfaces, were unchanged over time. The percent of ill participants who worked from home (7 vs 9 vs 3%, P= .02) and missed work due to ARI (13 vs 8 vs 8%, P= .03) decreased over time (Fig 1B). Figure 1A.Participant reported illness-related health behaviors in the past week — Seattle, WA, 2019–2021.Figure 1B.Participant reported illness-related school or work impact in the past week due to illness — Seattle, WA, 2019–2021 Time periods were defined as: Period 1: 11/14/19 – 3/22/20 (pre-/early COVID-19 pandemic), Period 2: 3/23/20 – 12/10/20 (post-Washington State Stay at Home order), and Period 3: 12/11/20 – 6/19/21 (United States Food and Drug Administration Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine for those 16 years and older). Illness was defined per Acute Respiratory Illness (ARI) case definition: cough or two qualifying symptoms (fever, sore throat, runny nose, muscle or body aches, headache, difficulty breathing, fatigue, nausea or vomiting; for participants < 18 years of age, ear pain or drainage, rash, and diarrhea were also qualifying symptoms). Conclusion As the COVID-19 pandemic progressed, households with school-aged children engaged in isolation, social distancing, and masking more frequently in response to ARI. The impact of ARIs on work decreased during the pandemic. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain–specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies., Science Immunology, 7 (78), ISSN:2470-9468

Background Characterizing SARS-CoV-2 outbreaks on university campuses is critical for informed public health measures and understanding transmission dynamics. Figure 1.Dropbox and Kiosk Samples Collected September 10, 2021 to April 23, 2022. Methods Faculty, staff, and students at a major public university in Seattle, WA, USA were enrolled in a COVID-19 testing study. Individuals could test using observed self-swabs at on-campus kiosks or unobserved self-swabs using a kit and returning it to a dropbox on campus. Sample collection volume for observed self-swabs was limited by staffing and space. All samples were returned to the laboratory and tested for SARS-CoV-2 by qRT-PCR. Results From September 10, 2021 to April 23, 2022, 38,400 individuals were enrolled in the study. Of these individuals, 5,089 used dropboxes only, 14,421 used kiosks only, and 5,820 used both. A total of 21,653 dropbox swabs and 75,493 observed self-swabs were collected. Median age was similar between individuals using dropboxes and observed self-swabs (20 vs. 22 years). A greater proportion of dropbox users were students compared to faculty and staff (students made up 83% of dropbox only population, 75% of kiosk only, and 86% of both, χ² p-value< 0.0001). Symptom data was reported for 65,349 swabs. Dropbox users were less likely to have symptoms compared to observed self-swab users (24% of swabs vs. 54%, χ² p-value< 0.0001). SARS-CoV-2 positivity was slightly lower for dropboxes compared to kiosks (4% vs. 5%; p=0.001). Dropboxes were highly utilized during periods of increased testing demand, including after academic breaks and variant emergence (Figure 1). Of the total tests distributed for use, a greater proportion of dropbox kits were unable to be resulted (6%) compared to observed self-swab kits (0.02%). Conclusion Dropboxes provided a flexible, high-volume collection method at times of increased testing demand. Individuals who used dropboxes were less likely to report symptoms and slightly less likely to test positive, suggesting a role for dropbox utilization in high-risk asymptomatic individuals during periods of high community transmission on a university campus. Disclosures Geoffrey S. Gottlieb, MD, PhD, Abbott Molecular Diagnostics: Grant/Research Support|Alere Technologies: Grant/Research Support|BMGF: Grant/Research Support|BMS: Grant/Research Support|Cerus Corp.: Grant/Research Support|Gilead Sciences: Grant/Research Support|Janssen Pharmaceutica: Grant/Research Support|Merck & Co: Grant/Research Support|Roche Molecular Systems: Grant/Research Support|THERA Technologies/TaiMed Biologics: Grant/Research Support|ViiV Healthcare: Grant/Research Support Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Human parainfluenza viruses (HPIV) cause respiratory illness in individuals of all ages. However, HPIV epidemiology data in people experiencing homelessness (PEH) are limited. Methods We analyzed cross-sectional data from a clinical trial and SARS-CoV-2 surveillance study in 23 homeless shelters in King County, Washington from October 2019-May 2021. Questionnaires and nasal swab specimens were obtained from eligible participants at enrollment. Between October 2019-March 31, 2020, participants included those aged > 3 months with acute respiratory illness. Monthly shelter surveillance was also conducted where participants were recruited regardless of symptoms. With the community spread of SARS-CoV-2, the study design transitioned from a clinical trial to a SARS-CoV-2 surveillance study which expanded enrollment eligibility to include participants with or without symptoms from April 1, 2020, onward. Participants were not followed longitudinally but were permitted to enroll multiple times during the study period. Specimens were tested for HPIV 1-4 and other respiratory viruses using RT-PCR. Results Among 14,464 specimens, 32 were HPIV-positive from 29 participants (median age 9 years, range 0.3-64 years; 45% female; 28% Black; 10% with chronic conditions) of which 59% were children. Family shelters had the highest percentage of HPIV infections (Table). HPIV was detected every month before the community spread of SARS-CoV-2. All HPIV-positive samples in May 2021 came from a single family shelter (Figure). Only 67% of HPIV-positive participants had symptoms with runny nose, cough and sore throat the most commonly reported. HPIV co-detection with other respiratory viruses occurred in 19% of HPIV-positive specimens; Rhinovirus co-detection (16%) was the most common. Human Parainfluenza Encounters by Shelter Type Before and After April 1, 2020 Human Parainfluenza Positive Samples by Shelter Type Among Unique Participants Conclusion HPIV affected PEH of all ages with most cases in shelters with children. Coinciding with community-wide SARS-CoV-2 mitigation efforts, the number of HPIV infections were reduced. However, a cluster of HPIV infections still occurred within one family shelter. Shelter-specific public health measures including non-pharmaceutical interventions used during the COVID-19 pandemic may reduce HPIV infections among residents. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant 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 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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant-neutralizing antibody that is a strong candidate for clinical development. ispartof: SCIENCE vol:378 issue:6620 pages:619-+ ispartof: location:United States status: published

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.

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on details of the experimental assay. Here we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. But for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.

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.

Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P = 0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8), and a 1.07 (95% confidence interval: 0.58, 1.57; P

ImportanceFew US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for co-circulating endemic viruses, such as rhinovirus.ObjectiveTo understand how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these to the factors associated with rhinovirus test positivity.DesignThis test-negative design study used multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 22-month period.SettingKing County, Washington, June 2020-April 2022Participants23,278 symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study.ExposuresSelf-reported data for 15 demographic and health behavior variables and 16 symptoms.Main Outcome(s) and Measure(s)RT-PCR confirmed SARS-CoV-2 or rhinovirus infection.ResultsClose contact with a SARS-CoV-2 case (adjusted odds ratio, aOR 4.3, 95% CI 3.7-5.0) and loss of smell/taste (aOR 3.7, 95% CI 3.0-4.5) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated case (aOR 2.4, 95% CI 1.7-3.3) was associated with a lower odds of test positivity than contact with an unvaccinated case (aOR 4.4, 95% CI 2.7-7.3). Sore throat was associated with Omicron infection (aOR 2.3, 95% CI 1.6-3.2) but not Delta. Vaccine effectiveness for participants fully vaccinated with a booster dose was 43% (95% CI 11-63%) for Omicron and 92% (95% CI 61-100%) for Delta.Variables associated with rhinovirus test positivity included age Conclusions and RelevanceEstimated risk factors and symptoms associated with SARS-CoV-2 infection have changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and socioeconomic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection, although the causal pathways remain unclear. Trends in testing behavior and availability may influence these results.Key PointsQuestionWhat are the characteristics associated with SARS-CoV-2 and rhinovirus infection?FindingsIn this test-negative design study of 23,278 participants, reporting close contact with a SARS-CoV-2 case was the strongest risk factor associated with test positivity. Loss of smell and taste was associated with the Delta variant, but not the Omicron variant. Vaccination and prior infection provided greater protection against Delta infection than Omicron Infection. Young age was the strongest predictor of rhinovirus positivity. Sociodemographic disparities were present for both SARS-CoV-2 and rhinovirus.MeaningMonitoring factors associated with respiratory pathogen test positivity remains important to identify at-risk populations in the post-SARS-CoV-2 pandemic period.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%−66.7%) to 31.5% (95% CI, 25.7%− 38.0%) but increased specificity from 77.5% (95% CI, 75.3%−79.5%) to 93.8% (95% CI, 92.7%−94.8%).

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.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1–receptor binding domain (RBD) and S1–N-terminal domain. For diagnosis, the combined [IgA + IgG + IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values ≥0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients—a possible source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2–4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19–vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2–specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines.

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.