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Background High-throughput sequencing provides a powerful window into the structural and functional profiling of microbial communities, but it is unable to characterize only the viable portion of microbial communities at scale. There is as yet not one best solution to this problem. Previous studies have established viability assessments using propidium monoazide (PMA) treatment coupled with downstream molecular profiling (e.g., qPCR or sequencing). While these studies have met with moderate success, most of them focused on the resulting “viable” communities without systematic evaluations of the technique. Here, we present our work to rigorously benchmark “PMA-seq” (PMA treatment followed by 16S rRNA gene amplicon sequencing) for viability assessment in synthetic and realistic microbial communities. Results PMA-seq was able to successfully reconstruct simple synthetic communities comprising viable/heat-killed Escherichia coli and Streptococcus sanguinis . However, in realistically complex communities (computer screens, computer mice, soil, and human saliva) with E. coli spike-in controls, PMA-seq did not accurately quantify viability (even relative to variability in amplicon sequencing), with its performance largely affected by community properties such as initial biomass, sample types, and compositional diversity. We then applied this technique to environmental swabs from the Boston subway system. Several taxa differed significantly after PMA treatment, while not all microorganisms responded consistently. To elucidate the “PMA-responsive” microbes, we compared our results with previous PMA-based studies and found that PMA responsiveness varied widely when microbes were sourced from different ecosystems but were reproducible within similar environments across studies. Conclusions This study provides a comprehensive evaluation of PMA-seq exploring its quantitative potential in synthetic and complex microbial communities, where the technique was effective for semi-quantitative purposes in simple synthetic communities but provided only qualitative assessments in realistically complex community samples. EyEgNYzCgS5Wz3QaRKFLLv Video abstract

Since March 2020, the United States has lost over 580,000 lives to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. A growing body of literature describes population-level SARS-CoV-2 exposure, but studies of antibody seroprevalence within school systems are critically lacking, hampering evidence-based discussions on school reopenings. The Lake Central School Corporation (LCSC), a public school system in suburban Indiana, USA, assessed SARS-CoV-2 seroprevalence in its staff and identified correlations between seropositivity and subjective histories and demographics. This study is a cross-sectional, population-based analysis of the seroprevalence of SARS-CoV-2 in LCSC staff measured in July 2020. We tested for seroprevalence with the Abbott Alinity™ SARS-CoV-2 IgG antibody test. The primary outcome was the total seroprevalence of SARS-CoV-2, and secondary outcomes included trends of antibody presence in relation to baseline attributes. 753 participants representative of the staff at large were enrolled. 22 participants (2.9%, 95% CI: 1.8% - 4.4%) tested positive for SARS-CoV-2 antibodies. Correcting for test performance parameters, the seroprevalence is estimated at 1.7% (90% Credible Interval: 0.27% - 3.3%). Multivariable logistic regression including mask wearing, travel history, symptom history, and contact history revealed a 48-fold increase in the odds of seropositivity if an individual previously tested positive for COVID-19 (OR: 48, 95% CI: 4–600). Amongst individuals with no previous positive test, exposure to a person diagnosed with COVID-19 increased the odds of seropositivity by 7-fold (OR: 7.2, 95% CI: 2.6–19). Assuming the presence of antibodies is associated with immunity against SARS-CoV-2 infection, these results demonstrate a broad lack of herd immunity amongst the school corporation’s staff irrespective of employment role or location. Protective measures like contact tracing, face coverings, and social distancing are therefore vital to maintaining the safety of both students and staff as the school year progresses.

Background Staphylococcus aureus is a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carry S. aureus asymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influence S. aureus acquisition and retention in early life. Results We recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, particularly within the first 2 months. It is weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns of S. aureus carriage, positively associated with Acinetobacter species, Streptococcus parasanguinis , Streptococcus salivarius , and Veillonella species and inversely associated with maternal Dolosigranulum pigrum . Furthermore, we identify a gene family, likely acting as a taxonomic marker for an unclassified species, that is significantly anti-correlated with S. aureus in infants and mothers. In gene content-based strain profiling, infant S. aureus strains are more similar to maternal strains. Conclusions This improved understanding of S. aureus colonization is an important first step toward the development of novel, ecological therapies for controlling S. aureus carriage.

On September 1, 2022, bivalent COVID-19 mRNA vaccines, composed of components from the SARS-CoV-2 ancestral and Omicron BA.4/BA.5 strains, were recommended by the Advisory Committee on Immunization Practices (ACIP) to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance (1). Initial recommendations included persons aged ≥12 years (Pfizer-BioNTech) and ≥18 years (Moderna) who had completed at least a primary series of any Food and Drug Administration-authorized or -approved monovalent vaccine ≥2 months earlier (1). On October 12, 2022, the recommendation was expanded to include children aged 5-11 years. At the time of recommendation, immunogenicity data were available from clinical trials of bivalent vaccines composed of ancestral and Omicron BA.1 strains; however, no clinical efficacy data were available. In this study, effectiveness of the bivalent (Omicron BA.4/BA.5-containing) booster formulation against symptomatic SARS-CoV-2 infection was examined using data from the Increasing Community Access to Testing (ICATT) national SARS-CoV-2 testing program.* During September 14-November 11, 2022, a total of 360,626 nucleic acid amplification tests (NAATs) performed at 9,995 retail pharmacies for adults aged ≥18 years, who reported symptoms consistent with COVID-19 at the time of testing and no immunocompromising conditions, were included in the analysis. Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of ≥2 monovalent vaccine doses among persons for whom 2-3 months and ≥8 months had elapsed since last monovalent dose was 30% and 56% among persons aged 18-49 years, 31% and 48% among persons aged 50-64 years, and 28% and 43% among persons aged ≥65 years, respectively. Bivalent mRNA booster doses provide additional protection against symptomatic SARS-CoV-2 in immunocompetent persons who previously received monovalent vaccine only, with relative benefits increasing with time since receipt of the most recent monovalent vaccine dose. Staying up to date with COVID-19 vaccination, including getting a bivalent booster dose when eligible, is critical to maximizing protection against COVID-19 (1).

In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.

Microbial communities and their associated bioactive compounds 1 – 3 are often disrupted in conditions such as the inflammatory bowel diseases (IBD) 4 . However, even in well-characterized environments (for example, the human gastrointestinal tract), more than one-third of microbial proteins are uncharacterized and often expected to be bioactive 5 – 7 . Here we systematically identified more than 340,000 protein families as potentially bioactive with respect to gut inflammation during IBD, about half of which have not to our knowledge been functionally characterized previously on the basis of homology or experiment. To validate prioritized microbial proteins, we used a combination of metagenomics, metatranscriptomics and metaproteomics to provide evidence of bioactivity for a subset of proteins that are involved in host and microbial cell–cell communication in the microbiome; for example, proteins associated with adherence or invasion processes, and extracellular von Willebrand-like factors. Predictions from high-throughput data were validated using targeted experiments that revealed the differential immunogenicity of prioritized Enterobacteriaceae pilins and the contribution of homologues of von Willebrand factors to the formation of Bacteroides biofilms in a manner dependent on mucin levels. This methodology, which we term MetaWIBELE (workflow to identify novel bioactive elements in the microbiome), is generalizable to other environmental communities and human phenotypes. The prioritized results provide thousands of candidate microbial proteins that are likely to interact with the host immune system in IBD, thus expanding our understanding of potentially bioactive gene products in chronic disease states and offering a rational compendium of possible therapeutic compounds and targets. A computational system termed MetaWIBELE (workflow to identify novel bioactive elements in the microbiome) is used to identify microbial gene products that are potentially bioactive and have a functional role in the pathogenesis of inflammatory bowel disease.

Among persons vaccinated with the adenovirus-based vaccine who received a booster dose of an mRNA vaccine, protection against the omicron variant was assessed. A single booster dose of an mRNA vaccine in recipients of a single priming dose of Ad26.COV2.S provided protection close to that of a three-dose mRNA vaccine regimen.

The SARS-CoV-2 Omicron sublineage XBB was first detected in the United States in August 2022.* XBB together with a sublineage, XBB.1.5, accounted for >50% of sequenced lineages in the Northeast by December 31, 2022, and 52% of sequenced lineages nationwide as of January 21, 2023. COVID-19 vaccine effectiveness (VE) can vary by SARS-CoV-2 variant; reduced VE has been observed against some variants, although this is dependent on the health outcome of interest. The goal of the U.S. COVID-19 vaccination program is to prevent severe disease, including hospitalization and death (1); however, VE against symptomatic infection can provide useful insight into vaccine protection against emerging variants in advance of VE estimates against more severe disease. Data from the Increasing Community Access to Testing (ICATT) national pharmacy program for SARS-CoV-2 testing were analyzed to estimate VE of updated (bivalent) mRNA COVID-19 vaccines against symptomatic infection caused by BA.5-related and XBB/XBB.1.5-related sublineages among immunocompetent adults during December 1, 2022–January 13, 2023. Reduction or failure of spike gene (S-gene) amplification (SGTF) in real-time reverse transcription–polymerase chain reaction (RT-PCR) was used as a proxy indicator of infection with likely BA.5-related sublineages and S-gene target presence (SGTP) of infection with likely XBB/XBB.1.5-related sublineages (2). Among 29,175 nucleic acid amplification tests (NAATs) with SGTF or SGTP results available from adults who had previously received 2–4 monovalent COVID-19 vaccine doses, the relative VE of a bivalent booster dose given 2–3 months earlier compared with no bivalent booster in persons aged 18–49 years was 52% against symptomatic BA.5 infection and 48% against symptomatic XBB/XBB.1.5 infection. As new SARS-CoV-2 variants emerge, continued vaccine effectiveness monitoring is important. Bivalent vaccines appear to provide additional protection against symptomatic BA.5-related sublineage and XBB/XBB.1.5-related sublineage infections in persons who had previously received 2, 3, or 4 monovalent vaccine doses. All persons should stay up to date with recommended COVID-19 vaccines, including receiving a bivalent booster dose when they are eligible.

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance. Methods A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose). Results A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5–7 months post vaccination during the BA.4/BA.5 period. Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%–53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%–44%). In 50- to 64-year-olds, rVE estimates were similar. Conclusions Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time. Individuals with 1 or 2 monovalent mRNA COVID-19 booster doses were less likely to have symptomatic SARS-CoV-2 infection compared to those without booster doses, during the BA.2/BA.2.12.1 and BA.4/BA.5 predominant subvariant periods.

In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.