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High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron.

ABSTRACT: The early widespread dissemination of Omicron indicates the urgent need to better understand the transmission dynamics of this variant, including asymptomatic spread among immunocompetent and immunosuppressed populations. In early December 2021, the Ubuntu clinical trial, designed to evaluate efficacy of the mRNA-1273 vaccine (Moderna) among persons living with HIV (PLWH), began enrolling participants. Nasal swabs are routinely obtained at the initial vaccination visit, which requires participants to be clinically well to receive their initial jab. Of the initial 230 participants enrolled between December 2 and December 17, 2021, 71 (31%) were PCR positive for SARS-CoV-2: all of whom were subsequently confirmed by S gene dropout to be Omicron; 48% of the tested samples had cycle threshold (CT) values <25 and 18% less than 20, indicative of high titers of asymptomatic shedding. Asymptomatic carriage rates were similar in SARS-CoV-2 seropositive and seronegative persons (27% respectively). These data are in stark contrast to COVID-19 vaccine studies conducted pre-Omicron, where the SARS-CoV-2 PCR positivity rate at the first vaccination visit ranged from <1%-2.4%, including a cohort of over 1,200 PLWH largely enrolled in South Africa during the Beta outbreak. We also evaluated asymptomatic carriage in a sub study of the Sisonke vaccine trial conducted in South African health care workers, which indicated 2.6% asymptomatic carriage during the Beta and Delta outbreaks and subsequently rose to 16% in both PLWH and PHLWH during the Omicron period. These findings strongly suggest that Omicron has a much higher rate of asymptomatic carriage than other VOC and this high prevalence of asymptomatic infection is likely a major factor in the widespread, rapid dissemination of the variant globally, even among populations with high prior rates of SARS-COV-2 infection.

SUBMITTER: Garrett N

PROVIDER: S-EPMC8764727 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: We employed DNA microarray technology to investigate the host response to Streptococcus pneumoniae in a mouse model of asymptomatic carriage. Over a period of six weeks, we profiled transcript abundance and complexity in the Nasal Associated Lymphoid Tissue (NALT) to identify genes whose expression differed between pneumococcal-colonized and uncolonized states. Results: Colonization with S. pneumoniae altered the expression of hundreds of genes over the course of the study, demonstrating that carriage is a dynamic process characterized by increased expression of a set of early inflammatory responses, including induction of a Type 1 Interferon response, and the production of several antimicrobial factors. Subsequent to this initial inflammatory response, we observed increases in transcripts associated with T cell development and activation, as well as wounding, basement membrane remodeling, and cell proliferation. Our analysis suggests that microbial colonization induced expression of genes encoding components critical for controlling JAK/STAT signaling, including stat1, stat2, socs3, and mapk1, as well as induction of several Type 1 Interferon-inducible genes and other antimicrobial factors at the earliest stages of colonization. Conclusions: Examining multiple time points over six weeks of colonization demonstrated that asymptomatic carriage stimulates a dynamic host response characterized by temporal waves with distinct biological programs. Our data suggest that the usual response to the presence of the pneumocccus is an initial controlled inflammatory response followed by activation of host physiological processes such as response to wounding, basement membrane remodeling, and increasing cellular numbers that ultimately allow the host to maintain an intact epithelium and eventually mount a preventive adaptive immune response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied.

Project description:BackgroundAsymptomatic infections are potential sources of transmission for coronavirus disease 2019, especially during the epidemic of the SARS-CoV-2 Omicron variant. We aimed to assess the percentage of asymptomatic infections among SARS-CoV-2 Omicron variant-positive individuals detected by gene sequencing or specific polymerase chain reaction (PCR).MethodsWe searched PubMed, EMBASE, and Web of Science from 26 November 2021 to 13 April 2022. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (CRD42022327894). Three researchers independently extracted data and two researchers assessed quality using pre-specified criteria. The pooled percentage with 95% confidence interval (CI) of asymptomatic infections of SARS-CoV-2 Omicron was estimated using random-effects models.ResultsOur meta-analysis included eight eligible studies, covering 7640 Omicron variant-positive individuals with 2190 asymptomatic infections. The pooled percentage of asymptomatic infections was 32.40% (95% CI: 25.30-39.51%) among SARS-CoV-2 Omicron variant-positive individuals, which was higher in the population in developing countries (38.93%; 95% CI: 19.75-58.11%), with vaccine coverage ≥ 80% (35.93%; 95% CI: 25.36-46.51%), with a travel history (40.05%; 95% CI: 7.59-72.51%), community infection (37.97%; 95% CI: 10.07-65.87%), and with a median age < 20 years (43.75%; 95% CI: 38.45-49.05%).ConclusionIn this systematic review and meta-analysis, the pooled percentage of asymptomatic infections was 32.40% among SARS-CoV-2 Omicron variant-positive individuals. The people who were vaccinated, young (median age < 20 years), had a travel history, and were infected outside of a clinical setting (community infection) had higher percentages of asymptomatic infections. Screening is required to prevent clustered epidemics or sustained community transmission caused by asymptomatic infections of Omicron variants, especially for countries and regions that have successfully controlled SARS-CoV-2.

Project description:BackgroundStaphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus.Principal findingsWe characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA).SignificanceThis investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.

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High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron.

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