Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha,Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study

BackgroundThe continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period.Methods and findingsA Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: −0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals.ConclusionsTwo vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Mie Agermose Gram and colleagues estimate vaccine effectiveness against infection and COVID-19 hospitalization with the Alpha, Delta or Omicron variant in Denmark.     

An Anatomical Description of a Miniaturized Acorn Worm (Hemichordata,Enteropneusta) with Asexual Reproduction by Paratomy

The interstitial environment of marine sandy bottoms is a nutrient-rich, sheltered habitat whilst at the same time also often a turbulent, space-limited, and ecologically challenging environment dominated by meiofauna. The interstitial fauna is one of the most diverse on earth and accommodates miniaturized representatives from many macrofaunal groups as well as several exclusively meiofaunal phyla. The colonization process of this environment, with the restrictions imposed by limited space and low Reynolds numbers, has selected for great morphological and behavioral changes as well as new life history strategies.Here we describe a new enteropneust species inhabiting the interstices among sand grains in shallow tropical waters of the West Atlantic. With a maximum body length of 0.6 mm, it is the first microscopic adult enteropneust known, a group otherwise ranging from 2 cm to 250 cm in adult size. Asexual reproduction by paratomy has been observed in this new species, a reproductive mode not previously reported among enteropneusts.Morphologically, Meioglossus psammophilus gen. et sp. nov. shows closest resemblance to an early juvenile stage of the acorn worm family Harrimaniidae, a result congruent with its phylogenetic placement based on molecular data. Its position, clearly nested within the larger macrofaunal hemichordates, suggests that this represents an extreme case of miniaturization. The evolutionary pathway to this simple or juvenile appearance, as chiefly demonstrated by its small size, dense ciliation, and single pair of gill pores, may be explained by progenesis. The finding of M. psammophilus gen. et sp. nov. underscores the notion that meiofauna may constitute a rich source of undiscovered metazoan diversity, possibly disguised as juveniles of other species.     

Protein Disulfide-Isomerase Interacts with a Substrate Protein at All Stages along Its Folding Pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a K_d of ca. 10⁻⁵ M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI''s interaction with a partly-folded protein, and the first to analyze this folding catalyst''s changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility.     

Strain Diversity of CTX-M-Producing Enterobacteriaceae in Individual Pigs: Insights into the Dynamics of Shedding during the Production Cycle

The aim of this study was to evaluate the population dynamics of CTX-M-producing Enterobacteriaceae in individual pigs on a farm positive for CTX-M-14-producing Escherichia coli. Fecal samples were collected once around the farrowing time from five sows and four times along the production cycle from two of their respective offspring. Multiple colonies per sample were isolated on cefotaxime-supplemented MacConkey agar with or without prior enrichment, resulting in 98 isolates identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry and tested for bla_CTX-M. CTX-M-positive isolates (n = 86) were typed by pulsed-field gel electrophoresis (PFGE). Plasmids harboring bla_CTX-M were characterized in 22 representative isolates by replicon typing and restriction fragment length polymorphism. Based on the PFGE results, all individuals shed unrelated CTX-M-14-producing E. coli strains during the course of life. Concomitant shedding of CTX-M-2/97-producing Proteus mirabilis or Providencia rettgeri was observed in two sows and two offspring. At least two genetically unrelated CTX-M-producing E. coli strains were isolated from approximately one-fourth of the samples, with remarkable differences between isolates obtained by enrichment and direct plating. A clear decrease in strain diversity was observed after weaning. Dissemination of bla_CTX-M-14 within the farm was attributed to horizontal transfer of an IncK plasmid that did not carry additional resistance genes and persisted in the absence of antimicrobial selective pressure. Assessment of strain diversity was shown to be influenced by the production stage from which samples were collected, as well as by the isolation method, providing useful information for the design and interpretation of future epidemiological studies of CTX-M-producing Enterobacteriaceae in pig farms.     

Evolution of cave suspension feeding in Protodrilidae (Annelida)

Protodrilidae belongs in a lineage that until now entirely consisted of deposit‐feeding, highly adapted interstitial annelids. Except for a pair of anterior palps, all protodrilids lack appendages, parapodia and chaetae; and have slender bodies adapted to glide between the sand grains by ciliary motion. The first exception to these characteristics is Megadrilus pelagicus n. sp. inhabiting the water column of the anchialine La Corona cave system in Lanzarote. Its morphology and evolutionary history are here investigated by combining observations from in vivo video recordings and advanced microscopy with phylogenetic analyses. Our studies revealed a unique pelagic, suspension feeding behaviour attained by its long ciliated palps in combination with an autopomorphic dorsal ciliated keel and several longitudinal and transverse ciliary bands. Phylogenetic analyses recovered Megadrilus pelagicus n. sp. nested within Protodrilidae indicating that its unique traits are derived within the family. These traits are traced in the tree topologies in correlation to cave colonization. The evolution of these traits can be functionally explained by the different demands of a pelagic suspension feeding strategy compared to the ancestral deposit‐feeding guild of the family. The origin of this suspension feeding strategy was presumably favoured by the partial isolation of the anchialine ecosystem, connected to the sea only through the highly porous volcanic subterranean bedrock. This crevicular connection limits the amount of predators and turbulence in the cave, but allows continuous water flow into the system carrying organic particles, which is the main source of food when photosynthetic primary production does not occur and sedimentation is limited. These conditions may select for pelagic suspension feeding as the most feasible life‐strategy in anchialine caves, which the dominance of pelagic, suspension feeding crustaceans and annelids in anchialine cave assemblages may also reflect. For species of ancestrally deposit‐feeding lineages entering the cave system, such as the annelid families Protodrilidae and Nerillidae, an adaptive‐shift from interstitial to crevicular habitats seemingly correlates with dramatic morphological changes and speciation. The dramatic changes observed in these primarily interstitial lineages compared to their relatives, point to alternative adaptive evolutionary pathways related to ecological fitness contrary to the previously proposed theories focusing on geological or stochastic processes.     

Psychopathology in 7‐year‐old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder – The Danish High Risk and Resilience Study ‐ VIA 7, a population‐based cohort study

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR‐SZ) or bipolar disorder (FHR‐BP) with population‐based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven‐year‐old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM‐IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School‐Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD‐Rating Scale, the Test Observation Form, and the State‐Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR‐SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2‐5.7, p < 0.001) and FHR‐BP children (35.6%, OR=3.1, 95% CI: 1.8‐5.3, p < 0.001) compared with controls (15.2%). FHR‐SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR‐BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR‐SZ children. Level of functioning was lower in both FHR‐SZ children (CGAS mean score = 68.2; 95% CI: 66.3‐70.2, p < 0.0001) and FHR‐BP children (73.7; 95% CI: 71.2‐76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9‐79.9). In conclusion, already at the age of seven, FHR‐SZ and FHR‐BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children.     

Unique Substrate Specificity of SplE Serine Protease from Staphylococcus aureus

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Similarity of growth among Great tits (Parus major) and Blue tits (P. caeruleus)

Differences in morphology among species are proximately caused by changes in the ontogeny of individuals. It is therefore of importance to analyse possible differences in growth parameters among closely related species in order to understand what parameters are most and least likely, respectively, to change in evolution. In this paper I analyse growth in two closely related sympatric species, namely Great tit, Parus major, and Blue tit, P. caeruleus. The former is considerably larger than the latter in all external traits. The growth rates of the two species were found to be very similar for all traits, thus excluding differences in growth rate as a potential cause of evolutionary size changes. Offset of growth occurred at relatively similar times in the two species, excluding this factor as a major cause of the final size differences. However, size differences at hatching were pronounced and remained so throughout ontogeny, pointing to initial size (egg size or hatching size) as the target of factors promoting change. Bivariate allometric relations of traits vs. body size (mass) were similar between the two species at all ontogenetic stages. There was a high correlation among traits especially at intermediate age stages (5 and 8 days), but these correlations became weaker at older age and approached the low pattern of integration found in adults. All this suggests the operation of a general growth factor affecting all parts of the phenotype simultaneously, which has its major influence at the time of maximal growth. If closely related species in general have highly similar growth patterns, strong evolutionary allometry as found in many avian taxa is to be expected.