Abstract
Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) ...pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host’s innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.
ABSTRACT All-sky multiband photometric surveys represent a unique opportunity of exploring rich nearby galaxy clusters up to several virial radii, reaching the filament regions where pre-processing ...is expected to occur. These projects aim to tackle a large number of astrophysical topics, encompassing both the Galactic and extragalactic fields. In that sense, generating large catalogues with homogeneous photometry for both resolved and unresolved sources that might be interesting to achieve specific goals, imposes a compromise when choosing the set of parameters to automatically detect and measure such a plethora of objects. In this work, we present the acquired experience on studying the galaxy content of the Fornax cluster using large catalogues obtained by the Southern Photometric Local Universe Survey (S-PLUS). We realized that some Fornax bright galaxies are missed in the S-PLUS iDR4 catalogues. In addition, Fornax star-forming galaxies are included as multiple detections due to overdeblending. To solve those issues, we performed specific SExtractor runs to identify the proper set of parameters to recover as many Fornax galaxies as possible with confident photometry and avoiding duplications. From that process, we obtained new catalogues containing 12-band improved photometry for ∼ 3 × 106 resolved and unresolved sources in an area of ∼ 208 deg2 in the direction of the Fornax cluster. Together with identifying the main difficulties to carry out the study of nearby groups and clusters of galaxies using S-PLUS catalogues, we also share possible solutions to face issues that seem to be common to other ongoing photometric surveys.
In this study, we report the first case of intra-host SARS-CoV-2 recombination during a coinfection by the variants of concern (VOC) AY.33 (Delta) and P.1 (Gamma) supported by sequencing reads ...harboring a mosaic of lineage-defining mutations. By using next-generation sequencing reads intersecting regions that simultaneously overlap lineage-defining mutations from Gamma and Delta, we were able to identify a total of six recombinant regions across the SARS-CoV-2 genome within a sample. Four of them mapped in the spike gene and two in the nucleocapsid gene. We detected mosaic reads harboring a combination of lineage-defining mutations from each VOC. To our knowledge, this is the first report of intra-host RNA-RNA recombination between two lineages of SARS-CoV-2, which can represent a threat to public health management during the COVID-19 pandemic due to the possibility of the emergence of viruses with recombinant phenotypes.
Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive ...pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction.
We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction.
Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p<0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was −91·6% in Brazil (530 72·9% of 727 before, 27 6·1% of 441 after); −85·0% in Chile (613 72·6% of 844 before, 44 10·9% of 404 after); −84·7% in Colombia (231 63·1% of 366 before, 34 9·7% of 352 after); and −73·8% in Paraguay (127 77·0% of 165 before, 22 20·2% of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was −59·6% in Argentina (853 85·0% of 1003 before, 149 34·3% of 434 after); −16·5% in the Dominican Republic (95 80·5% of 118 before, 39 67·2% of 58 after); −43·7% in Mexico (202 73·2% of 276 before, 63 41·2% of 153 after); and −45·9% in Uruguay (138 80·7% of 171 before, 38 43·7% of 87 after). Annual reporting rates showed a reduction from −82·5% (6·21 before vs 1·09 after per 100 000, 95% CI −61·6 to −92·0) to −94·7% (1·15 vs 0·06 per 100 000, −89·7 to −97·3) for PCV10 countries, and −58·8% (2·98 vs 1·23 per 100 000, −21·4 to −78·4) to −82·9% (7·80 vs 1·33 per 100 000, −76·9 to −87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period.
SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs.
None.
For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of first-principle QCD calculations to yield a ...precise description of the substructure of jets and study the accuracy of state-of-the-art Monte Carlo tools. Limitations of the experiments’ ability to resolve substructure are evaluated, with a focus on the impact of additional (pile-up) proton proton collisions on jet substructure performance in future LHC operating scenarios. A final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks.
During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of ...Rio de Janeiro. In this work, we have employed phylodynamic methods to analyse more than 1 600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.
Brazil currently ranks second in absolute deaths by COVID-19, even though most of its population has completed the vaccination protocol. With the introduction of Omicron in late 2021, the number of ...COVID-19 cases soared once again in the country. We investigated in this work how lineages BA.1 and BA.2 entered and spread in the country by sequencing 2173 new SARS-CoV-2 genomes collected between October 2021 and April 2022 and analyzing them in addition to more than 18,000 publicly available sequences with phylodynamic methods. We registered that Omicron was present in Brazil as early as 16 November 2021 and by January 2022 was already more than 99% of samples. More importantly, we detected that Omicron has been mostly imported through the state of São Paulo, which in turn dispersed the lineages to other states and regions of Brazil. This knowledge can be used to implement more efficient non-pharmaceutical interventions against the introduction of new SARS-CoV variants focused on surveillance of airports and ground transportation.
The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.
To ...determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.
Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.
An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.
The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.
A total of 1010 patients (37.5% female; mean SD age, 50.9 17.4 years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio HR, 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.
In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.
clinicaltrials.gov Identifier: NCT01374022.
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