The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. ...Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta.
The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred.
We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate.
Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak.
These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts.
Fitness recovery of HIV-1 "in vitro" was studied using viral clones that had their fitness decreased as a result of plaque-to-plaque passages.
After ten large population passages, the viral ...populations showed an average increase of fitness, although with wide variations among clones. While 5 clones showed significant fitness increases, 3 clones showed increases that were only marginally significant (p<0.1), and 4 clones did not show any change. Fitness recovery was not accompanied by an increase in p24 production, but was associated with an increase in viral titer. Few mutations (an average of 2 mutations per genome) were detected in the consensus nucleotide sequence of the entire genome in all viral populations. Five of the populations did not fix any mutation, and three of them displayed marginally significant fitness increases, illustrating that fitness recovery can occur without detectable alterations of the consensus genomic sequence. The investigation of other possible viral factors associated with the initial steps of fitness recovery, showed that viral quasispecies heterogeneity increased between the initial clones and the passaged populations. A direct statistical correlation between viral heterogeneity and viral fitness was obtained.
Thus, the initial fitness recovery of debilitated HIV-1 clones was mediated by an increase in quasispecies heterogeneity. This observation, together with the invariance of the consensus sequence despite fitness increases demonstrates the relevance of quasispecies heterogeneity in the evolution of HIV-1 in cell culture.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SARS-CoV-2 genomics and impact on clinical care for COVID-19 Lorenzo-Redondo, Ramon; de Sant’Anna Carvalho, Alexandre Machado; Hultquist, Judd F ...
Journal of antimicrobial chemotherapy,
11/2023, Letnik:
78, Številka:
Supplement_2
Journal Article
Recenzirano
Odprti dostop
Abstract
The emergence and worldwide spread of SARS-CoV-2 during the COVID-19 pandemic necessitated the adaptation and rapid deployment of viral WGS and analysis techniques that had been previously ...applied on a more limited basis to other viral pathogens, such as HIV and influenza viruses. The need for WGS was driven in part by the low mutation rate of SARS-CoV-2, which necessitated measuring variation along the entire genome sequence to effectively differentiate lineages and characterize viral evolution. Several WGS approaches designed to maximize throughput and accuracy were quickly adopted by surveillance labs around the world. These broad-based SARS-CoV-2 genomic sequencing efforts revealed ongoing evolution of the virus, highlighted by the successive emergence of new viral variants throughout the course of the pandemic. These genomic insights were instrumental in characterizing the effects of viral mutations on transmissibility, immune escape and viral tropism, which in turn helped guide public health policy, the use of monoclonal antibody therapeutics and vaccine development strategies. As the use of direct-acting antivirals for the treatment of COVID-19 became more widespread, the potential for emergence of antiviral resistance has driven ongoing efforts to delineate resistance mutations and to monitor global sequence databases for their emergence. Given the critical role of viral genomics in the international effort to combat the COVID-19 pandemic, coordinated efforts should be made to expand global genomic surveillance capacity and infrastructure towards the anticipation and prevention of future pandemics.
To identify the impact of universal masking on COVID-19 incidence and putative SARS-CoV-2 transmissions events among children's hospital healthcare workers (HCWs).
Quasi-experimental study.
Single ...academic free-standing children's hospital.
We performed whole-genome sequencing of SARS-CoV-2- PCR-positive samples collected from HCWs 3 weeks before and 6 weeks after implementing a universal masking policy. Phylogenetic analyses were performed to identify clusters of clonally related SARS-CoV-2 indicative of putative transmission events. We measured COVID-19 incidence, SARS-CoV-2 test positivity rates, and frequency of putative transmission events before and after the masking policy was implemented.
HCW COVID-19 incidence and test positivity declined from 14.3 to 4.3 cases per week, and from 18.4% to 9.0%, respectively. Putative transmission events were only identified prior to universal masking.
A universal masking policy was associated with reductions in HCW COVID-19 infections and occupational acquisition of SARS-CoV-2.
Abstract
Background
SARS-CoV-2 infection in pregnancy can cause placental abnormalities such as “SARS-CoV-2 placentitis” (histiocytic intervillositis, perivillous fibrin deposition, and villous ...trophoblast necrosis) that is irrespective of infection severity and associated with stillbirth. Mechanisms of SARS-CoV-2 placental injury are poorly understood. We investigated gene expression through next generation sequencing (NGS)-based spatial transcriptomics of placentas from SARS-CoV-2 infection and controls.
Methods
Cases of SARS-CoV-2 in pregnancy with normal histopathology n=4, pandemic timeframe controls with normal histopathology n=2, and SARS-CoV-2 placentitis n=3 were examined using Amsterdam Criteria and CD68 staining. RNA was extracted from FFPE tissue and underwent 10x Genomics Visium spatial NGS. Gene expression was analyzed while retaining tissue structure (Fig 1). Sequences and images were processed with Space Ranger 1.3.1 and R Seurat v.4.1.1.51. Raw counts were normalized using SCTransform. The Louvain algorithm and t-SNE algorithm were used for clustering and visualization. Differentially expressed genes were identified with Seurat and MAST. Various downstream pathway and cell type enrichment analyses were performed on transcriptional clusters.Figure 1.Anatomy underlies placental gene expression heterogeneity.
Section of a control placenta in H&E (left) and colored spots based on Louvain clustering of gene expression (right). The basal plate (dark blue, #4) is an area of fibrin and decidua adjacent to the uterine wall. Oxygenated maternal blood enters at the basal plate. Areas of terminal villi adjacent to the basal plate (green, #2) receive the highest oxygen with relative hypoxia further from the basal plate (salmon, #0 --> yellow, #1; pink, #5 is a subset of salmon). Stem villi (aqua, #3), which carry fetal blood to and from the placenta, form their own cluster.
Results
Anatomic structures were related to gene expression clusters (basal plate, villi; Fig 1). Clinical data is in Table 1. Unique clusters were present in controls compared to SARS-CoV-2 placentas with normal histopathology (Fig 2). Genes upregulated in a distinct cluster in controls showed enrichment of macrophages and increased expression of cell regulation and viral responses, such as the interleukin 1 receptor-like 1 (IL1RL1), indicating dysregulation of normal immune responses in SARS-CoV-2 placentas. We found significantly upregulated genes in villous areas of placentitis (neutrophil degranulation and interferon signaling; Fig 3) compared to normal SARS-CoV-2 cases.Table 1.Clinical data and categorization of cases.* Latency = time between SARS-CoV-2 infection and delivery admission. Controls were defined as no SARS-CoV-2 infection in pregnancy, negative SARS-CoV-2 PCR on hospital admission screen, and negative anti-SARS-CoV-2 spike protein IgG/IgM at delivery.Figure 2.Enrichment of macrophages and interleukin 1 receptor-like 1 gene in unique cluster present in control placentas.A) Clusters overlying placental slides are shown. B) Control placentas with normal histopathology (n=2) on left and SARS-CoV-2 (COVID) placentas with normal histopathology on right ((n=4). C) Plot of enriched cell marker genes upregulated in cluster 2 highlights macrophages, MKi67+ progenitor cells, and fibroblasts. D) IL1RL1 gene is shown as an example of the set of genes significantly upregulated in control placentas compared to SARS-CoV-2 placentas.Figure 3.SARS-CoV-2 placentitis cases demonstrate increased expression of acute inflammatory activation compared to SARS-CoV-2 infection cases with normal histopathology.A) Gene expression cluster differences in normal SARS-CoV-2 (COVID) placentas and SARS-CoV-2 placentitis cases are shown. Placentitis shows decreased trophoblast transcripts and increased immune populations. B) Differential gene expression, especially surrounding live villi, demonstrate increased expression of acute inflammatory/immune activation genes including pathways such as neutrophil degranulation and multiple interferon families.
Conclusion
This spatial transcriptomic analysis shows differential gene expression in control and SARS-CoV-2 placentas. SARS-CoV-2 placentitis demonstrates distinct acute inflammatory activation, providing pathophysiologic insight. Further pathway analysis of SARS-CoV-2-associated placental phenotypes is ongoing.
Disclosures
All Authors: No reported disclosures
Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare ...three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.
IV-injected antibodies have demonstrated protection against SHIV infection in rhesus macaques paving the way for the AMP trial where at-risk individuals for HIV received an IV-infusion of the HIV ...bNAb, VRC01. However, the time needed for these antibodies to fully distribute and elicit protection at mucosal sites is still unknown. Here, we interrogate how long it takes for antibodies to achieve peak anatomical levels at the vaginal surface following IV-injection. Fluorescently-labeled VRC01 and/or Gamunex-C were IV-injected into 24 female rhesus macaques (
Macaca mulatta
) with vaginal tissues and plasma acquired up to 2-weeks post-injection. We found that antibody delivery to the vaginal mucosa occurs in two phases. The first phase involves delivery to the submucosa, occurring within 24hrs and persisting beyond 1 week. The second phase is the delivery through the stratified squamous epithelium, needing approximately 1 week to saturate the stratum corneum. This study has important implications for the efficacy of immunoprophylaxis targeting pathogens at the mucosa.
The objective of this single-center cohort study was to characterize the frequency, clinical characteristics, and molecular epidemiology of pediatric severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infection after vaccination. Between May 15, 2021, and January 1, 2022, 171 children experienced SARS-CoV-2 infection postvaccination, 146 (86%) following the Omicron variant predominance. Outcomes were generally mild and comparable before and after Omicron predominance.
To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 ...transmission in school and household contacts of these positive individuals.
In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried.
Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing.
We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.
i.v. injected Abs have demonstrated protection against simian HIV infection in rhesus macaques, paving the way for the Antibody Mediated Prevention trial in which at-risk individuals for HIV received ...an i.v. infusion of the HIV broadly neutralizing Ab VRC01. However, the time needed for these Abs to fully distribute and elicit protection at mucosal sites is still unknown. In this study, we interrogate how long it takes for Abs to achieve peak anatomical levels at the vaginal surface following i.v. injection. Fluorescently labeled VRC01 and/or Gamunex-C were i.v. injected into 24 female rhesus macaques (
) with vaginal tissues and plasma acquired up to 2 wk postinjection. We found that Ab delivery to the vaginal mucosa occurs in two phases. The first phase involves delivery to the submucosa, occurring within 24 h and persisting beyond 1 wk. The second phase is the delivery through the stratified squamous epithelium, needing ∼1 wk to saturate the stratum corneum. This study has important implications for the efficacy of immunoprophylaxis targeting pathogens at the mucosa.
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