Multiple early factors anticipate post-acute COVID-19 sequelae.

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 auto-antibodies. 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.

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

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

Remote Household Observation for Noninfluenza Respiratory Viral Illness.

BACKGROUND: Noninfluenza respiratory viruses are responsible for a substantial burden of disease in the United States. Household transmission is thought to contribute significantly to subsequent transmission through the broader community. In the context of the coronavirus disease 2019 (COVID-19) pandemic, contactless surveillance methods are of particular importance. METHODS: From November 2019 to April 2020, 303 households in the Seattle area were remotely monitored in a prospective longitudinal study for symptoms of respiratory viral illness. Enrolled participants reported weekly symptoms and submitted respiratory samples by mail in the event of an acute respiratory illness (ARI). Specimens were tested for 14 viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using reverse-transcription polymerase chain reaction. Participants completed all study procedures at home without physical contact with research staff. RESULTS: In total, 1171 unique participants in 303 households were monitored for ARI. Of participating households, 128 (42%) included a child aged <5 years and 202 (67%) included a child aged 5-12 years. Of the 678 swabs collected during the surveillance period, 237 (35%) tested positive for 1 or more noninfluenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in 3 households. CONCLUSIONS: This study highlights the circulation of respiratory viruses within households during the winter months during the emergence of the SARS-CoV-2 pandemic. Contactless methods of recruitment, enrollment, and sample collection were utilized throughout this study and demonstrate the feasibility of home-based, remote monitoring for respiratory infections.

Evaluating Specimen Quality and Results from a Community-Wide, Home-Based Respiratory Surveillance Study.

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.

SwabExpress: An End-to-End Protocol for Extraction-Free COVID-19 Testing.

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.

Effects of weather-related social distancing on city-scale transmission of respiratory viruses: a retrospective cohort study.

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.

Clinical Features and Outcomes of 105 Hospitalized Patients With COVID-19 in Seattle, Washington.

BACKGROUND: Washington 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. METHODS: All 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. RESULTS: One 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%. CONCLUSIONS: During 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.

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

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

Infectious Disease Updates for Primary Care.

This article summarizes the situation with public health threats for primary care patients as of early 2024 and provides updates on strategies for the prevention, diagnosis, and treatment of common infections where new treatments and vaccines are available. For flu and COVID, an update on treatment is also provided-along with pearls useful for the busy primary care provider. The authors also discuss a new treatment option for drug-resistant vulvovaginal candidiasis and provide a balanced view of the increasingly popular technique of preventing bacterial sexually transmitted infections using doxycycline after condomless sex among men who have sex with men.