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Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation.

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion1and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry2,3. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning4to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456 and 473; however, the antigenic effects of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however, many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.

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.

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.

In rural Nepal, multiple HMPV genotypes circulate simultaneously with an alternating predominance of a single genotype and definitive seasonality. No difference in viral load was detected by genotype and symptom severity was not correlatedwith RT-PCR cycle threshold or genotype.

Similar RSV antibody levels in Alaska-native (AN) and non-AN womenAN infants’ cord blood RSV antibody levels lowerMaternal and cord blood influenza antibody levels lower in AN women and infantsAN mother–infant pairs’ RSV antibody transfer ratios significantly lower

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.

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes on the basis of their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.

Respiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described.

•COVID-19 rapid antigen testing is likely to be cost-effective in homeless shelters.•Without COVID-19 antigen testing, PCR testing is optimal at low vaccine coverage.•Modeled findings help decision-makers quantify the value of shelter surveillance.

•Few studies on the pandemic's effect on respiratory illness-related behavior change•People with respiratory illness stayed home more and avoided contact with others•The COVID-19 pandemic did not affect illness-associated school or work absenteeism

The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings.

Influenza is an important cause of illness and morbidity for infants. Seasonal influenza vaccination during pregnancy aims to provide protection to mothers, but it can also provide immunity to infants. The precise influence of maternal vaccination on immunity in infants and how vaccine-elicited antibodies provide protection in some but not all infants is incompletely understood. We comprehensively profiled the transfer of functional antibodies and defined humoral factors contributing to immunity against influenza in a clinical trial of maternal influenza vaccination. Influenza-specific antibody subclass levels, Fc ɣ receptor (FCGR) binding levels, and antibody-dependent innate immune functions were all profiled in the mothers during pregnancy and at birth, as well as in cord blood. Vaccination increased influenza-specific antibody levels, antibody binding to FCGR, and specific antibody-dependent innate immune functions in both maternal and cord blood, with FCGR binding most enhanced via vaccination. Influenza-specific FCGR binding levels were lower in cord blood of infants who subsequently developed influenza infection. Collectively these data suggest that in addition to increased antibody amounts, the selective transfer of FCGR-binding antibodies contributes to the protective immune response in infants against influenza.

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

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivoprotective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

IMPORTANCE: Although patients with cancer are at an increased risk of infection-related complications, few studies have characterized their vulnerability to measles and mumps. Given the recent outbreaks and increased community vaccine hesitancy, understanding measles and mumps immunity within this population is vital. OBJECTIVES: To identify a point prevalence estimate of protective measles and mumps antibodies among ambulatory patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residual clinical plasma samples were obtained from consecutive patients with cancer at Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center in Seattle, Washington, in August 2019. These samples were tested for measles and mumps IgG using a commercial enzyme-linked immunosorbent assay. Patients without cancer were excluded from the analysis. EXPOSURES: Patient age, sex, self-reported race and ethnicity, primary disease, receipt of chemotherapy in the past 30 days before sample collection, hematopoietic cell transplant (HCT) history, and date of most recent intravenous immunoglobulin treatment were abstracted from electronic medical records. MAIN OUTCOMES AND MEASURES: Measles and mumps IgG seroprevalence, defined as the proportion of patients with positive antibody test results, was measured overall and among the subgroups. RESULTS: Of the 959 patients included in the analysis, 510 (53%) were male individuals and the mean (SD) age at sample collection was 60 (15) years. Most patients (576 [60%]) had a malignant solid tumor, and 383 patients (40%) had a hematologic malignant neoplasm; 146 patients (15%) had an HCT history. Overall, the seroprevalence of measles antibodies was 0.75 (95% CI, 0.72-0.78), and the seroprevalence of mumps antibodies was 0.62 (95% CI, 0.59-0.65). The lowest seroprevalences were among patients with a hematologic malignant neoplasm (0.63 for measles and 0.48 for mumps), those with a history of HCT (0.46 for measles and 0.29 for mumps), and those aged 30 to 59 years (0.49-0.63 for measles and 0.41-0.58 for mumps). CONCLUSIONS AND RELEVANCE: In this study, 25% of ambulatory patients with cancer lacked protective antibodies for measles and 38% lacked protective antibodies for mumps. Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population.

Deep mutational scanning shows that the mRNA-1273 RBD-binding antibody response is less affected by single viral mutations than the infection response.

Initial SARS-CoV-2 dynamics in Washington State were driven by regional interventions and introductions of variants differing in viral loads.

A major goal of current SARS-CoV-2 vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets of the SARS-CoV-2 antibody response is critical for vaccine design, diagnostics, and development of therapeutics. Here, we develop a pan-Coronavirus phage display library to map antibody binding sites at high resolution within the complete viral proteomes of all known human-infecting coronaviruses in patients with mild or moderate/severe COVID-19. We find the majority of immune responses to SARS-CoV-2 are targeted to the Spike protein, Nucleocapsid, and ORF1ab, and include sites of mutation in current variants of concern. Some epitopes are identified in the majority of samples while others are rare, and we find variation in the number of epitopes targeted between individuals. We find low levels of SARS-CoV-2 cross-reactivity in individuals with no exposure to the virus, and significant cross-reactivity with endemic human CoVs in convalescent sera from patients with COVID-19.

Background Rhinovirus is the most common cause of viral respiratory tract infections in children. Virologic predictors of lower respiratory tract infection (LRTI), such as viral load and the presence of another respiratory virus (coinfection), are not well characterized in pediatric outpatients. Methods Mid-nasal turbinate samples were collected from children presenting for care to the Seattle Children's Hospital emergency department (ED) or urgent care with a symptomatic respiratory infection between December 2011 and May 2013. A subset of samples was tested for rhinovirus viral load by real-time polymerase chain reaction. Clinical data were collected by chart reviews. Multivariate logistic regression was used to evaluate the relationship between viral load and coinfection and the risk for LRTI. Results Rhinovirus was the most frequent respiratory virus detected in children younger than 3 years. Of 445 patients with rhinovirus infection, 262 (58.9%) had LRTIs, 231 (51.9%) required hospital admission and 52 (22.5%) were hospitalized for 3 days or longer. Children with no comorbidities accounted for 142 (54%) of 262 rhinovirus LRTIs. Higher viral load was significantly associated with LRTI among illness episodes with rhinovirus alone (OR, 2.11; 95% confidence interval [CI], 1.24–3.58). Coinfection increased the risk of LRTI (OR, 1.83; 95% CI, 1.01–3.32). Conclusions Rhinovirus was the most common pathogen detected among symptomatic young children in a pediatric ED who had respiratory viral testing performed, with the majority requiring hospitalization. Higher rhinovirus viral load and coinfection increased disease severity. Virologic data may assist clinical decision making for children with rhinovirus infections in the pediatric ED.

Background The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. Methods We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher's exact tests. Results Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO2. Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. Conclusions Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation.