Deviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic.

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially in the United States (US) following the implementation of COVID-19-related non-pharmaceutical interventions but later rebounded with abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study from 2009 to 2023 in Chicago, Illinois, US, we examined RSV epidemiology, clinical severity, and genetic diversity. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings post-2020 and that hospitalized adults infected with RSV-A were at higher risk of intensive care admission than those with RSV-B. While population structures of RSV-A remained unchanged, RSV-B exhibited a genetic shift into geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.

Integration of individualized and population-level molecular epidemiology data to model COVID-19 outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk.

Altered RSV Epidemiology and Genetic Diversity Following the COVID-19 Pandemic.

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially following the implementation of non-pharmaceutical interventions to mitigate the COVID-19 pandemic but later rebounded with initially abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study, we examined RSV epidemiology, clinical severity, and genetic diversity in the years surrounding the COVID-19 pandemic. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings after 2020 and that hospitalized adults with RSV-A were at higher risk of needing intensive care than those with RSV-B. While the population structure of RSV-A remained unchanged, the population structure of RSV-B shifted in geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.

ViralVar: A Web Tool for Multilevel Visualization of SARS-CoV-2 Genomes.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased the demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. The majority of the currently available tools either require computational expertise to deploy them or limit user input to preselected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: (1) the visualization of the spatiotemporal dynamics of SARS-CoV-2 lineages and (2) a structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in pediatric, adult, and elderly populations (n > 1.7 million genomes). Whereas the spatiotemporal dynamics of the variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate the large-scale surveillance of circulating pathogens.

Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study.

BACKGROUND: Recent COVID-19 surges are attributed to emergence of more transmissible SARS-CoV-2 variants of concern (VOCs). The relative severity of VOCs in children is unknown. METHODS: We performed a single-center retrospective cohort study of children ≤18 years old diagnosed with COVID-19 from October 2020-February 2022 and whose SARS-CoV-2 isolate underwent Illumina sequencing. We measured the frequency of five markers of COVID-19 severity. Logistic regression models were fitted to estimate the odds of each severity marker with each VOC. RESULTS: Among 714 children, 471 (66.0%) were infected with a VOC: 96 (13.4%) alpha, 38 (5.3%) gamma, 119 (16.7%) delta, and 215 (30.1%) omicron. High-risk medical conditions and increasing age were independently associated with COVID-19 severity. After adjusting for age, race, ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha, delta, nor omicron was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 6.7, 95% CI 2.0-22.1); pharmacologic treatment (OR 5.7, 95% CI 1.2-26.8); respiratory support (OR 11.9, 95% CI 2.7-62.4); and severe disease per the WHO Clinical Progression Scale (OR 11.7, 95% CI 2.1-90.5). Upon subgroup analyses, omicron was independently associated with ICU admission and severe disease per the WHO Clinical Progression Scale in children without SARS-CoV-2 immunization or prior COVID-19 infection. CONCLUSIONS: Compared to non-VOC COVID-19, the gamma VOC was independently associated with increased COVID-19 severity, as was omicron in children without SARS-CoV-2 immunization or prior COVID-19 infection. SARS-CoV-2 vaccination and prior COVID-19 prevented severe outcomes during the omicron surge.

De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.

BACKGROUND: The continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts. METHODS: Nasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro. RESULTS: Our sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry. CONCLUSIONS: These observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.

Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria.

Disparities in SARS-CoV-2 genomic surveillance have limited our understanding of the viral population dynamics and may delay identification of globally important variants. Despite being the most populated country in Africa, Nigeria has remained critically under sampled. Here, we report sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. In early 2021, most isolates belonged to the Alpha "variant of concern" (VOC) or the Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after expansion of an otherwise rare Delta sub-lineage. Spike protein from the Eta variant conferred increased infectivity and decreased neutralization by convalescent sera in vitro. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally and represented a VOC in early 2021. These results demonstrate a distinct distribution of SARS-CoV-2 lineages in Nigeria, and emphasize the need for improved genomic surveillance worldwide.

Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study.

BACKGROUND: Recent surges in coronavirus 2019 disease (COVID-19) is attributed to the emergence of more transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs). However, the relative severity of SARS-CoV-2 VOCs in children is unknown. METHODS: This retrospective single-center cohort study was performed at the Ann & Robert H. Lurie Children's Hospital of Chicago, academic free-standing children's hospital. We included all children ≤ 18 years-old diagnosed with COVID-19 between October 15 th , 2020 and August 31 st , 2021 and whose SARS-CoV-2 isolate was sequenced using the Illumina platform. For each patient sample, we identified the SARS-CoV-2 lineage, which was assigned to one of the following groups: Non-VOC, alpha VOC, beta VOC, gamma VOC, or delta VOC. We measured frequency of 5 markers of COVID-19 severity: hospitalization; COVID-19 pharmacologic treatment; respiratory support; intensive care unit admission; and severe disease as classified by the COVID-19 World Health Organization (WHO) Clinical Progression Scale (severe disease; score ≥ 6). A series of logistic regression models were fitted to estimate odds of each severity marker with each VOC (in comparison to non-VOCs), adjusting for COVID-19 community incidence and demographic and clinical co-variates. RESULTS: During the study period, 2,025 patients tested positive for SARS-CoV-2; 1,422 (70.2%) had sufficient viral load to permit sequencing. Among the 499 (35.1%) patients whose isolate was sequenced, median (inter-quartile range) age was 7 (1,12) years; 256 (51.3%) isolates were a VOC: 96 (37.5%) alpha, 38 (14.8%) gamma, and 119 (46.5%) delta. After adjusting for age, Black race, Hispanic ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha nor delta was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 5.9, 95% CI 1.6-21.5, p =0.007), respiratory support (OR 8.3, 95% CI 1.5-56.3, p =0.02), and severe disease as classified by the WHO Clinical Progression Scale (OR 7.7, 95% CI 1.0-78.1, p =0.05). CONCLUSIONS: Compared to non-VOC COVID-19 infections, the gamma VOC, but not the alpha or delta VOCs, was associated with increased severity. These data suggest that recent increased in pediatric COVID-19 hospitalizations are related to increased delta COVID-19 incidence rather than increased delta virulence in children.

Coincident rapid expansion of two SARS-CoV-2 lineages with enhanced infectivity in Nigeria.

The emergence of new SARS-CoV-2 variants with enhanced transmissibility or decreased susceptibility to immune responses is a major threat to global efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Disparities in viral genomic surveillance capabilities and efforts have resulted in gaps in our understanding of the viral population dynamics across the globe. Nigeria, despite having the largest population of any nation in Africa, has had relatively little SARS-CoV-2 sequence data made publicly available. Here we report the whole-genome sequences of 74 SARS-CoV-2 isolates collected from individuals in Oyo State, Nigeria in January 2021. Most isolates belonged to either the B.1.1.7 Alpha "variant of concern" or the B.1.525 Eta lineage, which is currently considered a "variant of interest" containing multiple spike protein mutations previously associated with enhanced transmissibility and possible immune escape. Nigeria has the highest reported frequency of the B.1.525 lineage globally with phylogenetic characteristics consistent with a recent monophyletic origin and rapid expansion. Spike protein from the B.1.525 lineage displayed both increased infectivity and decreased neutralization by convalescent sera compared to Spike proteins from other clades. These results, along with indications that the virus is outpacing the B.1.1.7 lineage in Nigeria, suggest that the B.1.525 lineage represents another "variant of concern" and further underline the importance of genomic surveillance in undersampled regions across the globe.

One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases - Utah and Wisconsin, 2020

BackgroundApproximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pet cohabitants as a sub-study of an ongoing COVID-19 household transmission investigation. MethodsMammalian pets from households with [≥]1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April-May 2020. Demographic/exposure information, oropharyngeal, nasal, rectal, and fur swabs, feces, and blood were collected from enrolled pets and tested by rRT-PCR and virus neutralization assays. FindingsWe enrolled 37 dogs and 19 cats from 34 of 41 eligible households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dogs fur swabs (2%) tested positive by rRT-PCR at the first animal sampling. Among 47 pets with serological results from 30 households, eight (17%) pets (4 dogs, 4 cats) from 6 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40-100%) compared to households with no seropositive pet (median 37%; range: 13-100%) (p=0.01). Thirty-three pets with serologic results had frequent daily contact ([≥]1 hour) with the human index patient before the persons COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the human index patient after diagnosis and none (0%) were seropositive; of the 19 (58%) pets with continued contact, 4 (21%) were seropositive. InterpretationsSeropositive pets likely acquired infection from humans, which may occur more frequently than previously recognized. People with COVID-19 should restrict contact with animals. FundingCenters for Disease Control and Prevention, U.S. Department of Agriculture

Health Care Transition in Youth With Type 1 Diabetes and an A1C >9%: Qualitative Analysis of Pre-Transition Perspectives.

OBJECTIVE | To explore expectations for transition to adult care and experiences with transition planning among adolescents and young adults with type 1 diabetes and an A1C >9% at a tertiary care U.S. pediatric center. METHODS | We conducted semi-structured interviews in a purposive sample of patients 14-23 years of age who had had type 1 diabetes for at least 1 year and had an A1C >9%. A multidisciplinary team conducted iterative thematic analysis with deductive and inductive coding aided by NVivo software. RESULTS | Fourteen subjects participated (nine adolescents and five young adults, mean age 17.1 ± 3.2 years, 57% male, 79% Caucasian, 14% Hispanic, diabetes duration 8.2 ± 4.6 years, mean A1C 10.0 ± 0.8% for adolescents and 10.1 ± 0.7% for young adults). Qualitative analysis yielded four key themes. The first was lack of formal preparation; participants of all ages demonstrated a lack of preparation for transition and ignorance about the process, describing it as coming "out of the blue." The second was a desire for delayed and gradual transition; participants wanted to defer being "serious" about transition to a later/uncertain date, with a preference to "wait until I'm older" among all ages. Participants described ideal transition as a gradual process, taking place "a little at a time." The third was attachment to pediatric providers; participants demonstrated a nearly universal attachment to and "familiarity" with their pediatric diabetes care providers and expressed worries about an "uncomfortable" transition to adult providers. The fourth was concern about an impersonal adult care setting: participants perceived adult care as "formal," "scarier," and "tougher," with increased criticism about poor control; participants expressed fear that adult providers would not "know me" or appreciate "my diabetes journey." CONCLUSION | We demonstrated a lack of transition preparation and anxiety about transition and adult care among youth with type 1 diabetes and elevated A1C. Our results may help guide early, iterative pediatric transition counseling, with a special focus on addressing attachment and fears about adult diabetes care.

Impact of a depression counseling intervention on student pharmacists' confidence and comfortability: A pilot study.

INTRODUCTION: The objective of this study was to assess the impact of a mental health educational intervention on pharmacy students' confidence and comfortability when engaging in depression counseling. METHODS: Third-year pharmacy students completed two 15-item rating scales addressing confidence and comfortability about depression. The intervention was 2.5 hours long and included a depression overview, consumer educator presentation, motivational interviewing, and case studies. Surveys were administered at baseline, immediately after the intervention, and three months post intervention. Data were analyzed using paired t-tests and repeated measures analyses. RESULTS: Of the 23 students who participated in the intervention, 12 (52.2%) completed the three-month follow-up. Confidence increased significantly (p < 0.05) from 3.5 ± 0.5 to 4.1 ± 0.4 immediately post intervention and was sustained at three months post (3.9 ± 0.5). Similarly, comfortability increased significantly (p < 0.05) from 3.6 ± 0.4 to 4.1 ± 0.5 immediately post and was sustained at three months post (4.1 ± 0.6). Cronbach's alphas ranged from 0.90 to 0.96. CONCLUSION: Pharmacy students' depression counseling confidence and comfortability improved and was sustained after a 2.5-hour intervention with motivational interviewing, consumer education, and case studies.

I Want to Believe: A Short Psychobiography of Mary Baker Eddy.

The 18th and 19th centuries were beset with new religious movements in the United States: Shakers, Latter Day Saints, Millerites, and Seventh Day Adventists to name a few. One group, Christian Science, held radically different views than their counterparts and their origins lay in the most unlikely of places, a perpetually ill and poor woman from New Hampshire. Much has been said about Mary Baker Eddy: some say that she was a prophet, others that she was a fraud. Herein no such judgments are made. This study seeks to look into the life of Mary Baker Eddy from a psychological lens in the hopes that insight can be gained into the founding of the First Church of Jesus Christ Scientist and perhaps to allay the binary of Mrs. Eddy as either prophet or fanatic.