Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Nat Med ; 28(7): 1501-1508, 2022 07.
Article in English | MEDLINE | ID: covidwho-1900517

ABSTRACT

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.


Subject(s)
COVID-19 , Graft vs Host Disease , Humans , Mutation/genetics , SARS-CoV-2/genetics
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329186

ABSTRACT

In some immunocompromised patients with chronic SARS-CoV-2 infection, dramatic adaptive evolution occurs, with substitutions reminiscent of those in variants of concern (VOCs). Here, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of twenty-seven chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations, yet a subset of mutations associated with successful global transmission was absent from chronic infections. The emergence of these mutations might dictate when variants from chronic infections can dramatically spread onwards. Next, we tested the ability to predict antibody-evasion mutations from patient- and viral-specific features, and found that viral rebound is strongly associated with the emergence of antibody-evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody-evasion in particular niches in a patient's body. We suggest that a trade-off exists between antibody-evasion and transmissibility that potentially constrains VOC emergence, and that monitoring chronic infections may be a means to predict future VOCs.

4.
Open Forum Infect Dis ; 8(10): ofab120, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1462451

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight. METHODS: We report a large nosocomial outbreak in 1 of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that 1 of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole-genome sequencing of the virus of 14 infected individuals involved in the outbreak. RESULTS: Surprisingly, the results of whole-genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, 1 of which led to a cluster of 10 of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the 1 that arose from our initial investigation. CONCLUSIONS: These results underscore the important added value of using whole-genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

5.
Nat Med ; 27(8): 1379-1384, 2021 08.
Article in English | MEDLINE | ID: covidwho-1269391

ABSTRACT

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/virology , RNA, Messenger/genetics , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged
6.
Viruses ; 12(11)2020 11 16.
Article in English | MEDLINE | ID: covidwho-937552

ABSTRACT

Site-specific evolutionary rate shifts are defined as protein sites, where the rate of substitution has changed dramatically across the phylogeny. With respect to a given clade, sites may either undergo a rate acceleration or a rate deceleration, reflecting a site that was conserved and became variable, or vice-versa, respectively. Sites displaying such a dramatic evolutionary change may point to a loss or gain of function at the protein site, reflecting adaptation, or they may indicate epistatic interactions among sites. Here, we analyzed full genomes of HIV and SIV-1 and identified 271 rate-shifting sites along the HIV-1/SIV phylogeny. The majority of rate shifts occurred at long branches, often corresponding to cross-species transmission branches. We noted that in most proteins, the number of rate accelerations and decelerations was equal, and we suggest that this reflects epistatic interactions among sites. However, several accessory proteins were enriched for either accelerations or decelerations, and we suggest that this may be a signature of adaptation to new hosts. Interestingly, the non-pandemic HIV-1 group O clade exhibited a substantially higher number of rate-shift events than the pandemic group M clade. We propose that this may be a reflection of the height of the species barrier between gorillas and humans versus chimpanzees and humans. Our results provide a genome-wide view of the constraints operating on proteins of HIV-1 and SIV.


Subject(s)
Evolution, Molecular , HIV-1/genetics , Simian Immunodeficiency Virus/genetics , Animals , HIV Seropositivity/genetics , HIV Seropositivity/transmission , HIV-1/classification , Humans , Pan troglodytes , Phylogeny , Simian Immunodeficiency Virus/classification , Viral Proteins/chemistry , Viral Proteins/genetics
7.
Nat Commun ; 11(1): 5518, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-899925

ABSTRACT

Full genome sequences are increasingly used to track the geographic spread and transmission dynamics of viral pathogens. Here, with a focus on Israel, we sequence 212 SARS-CoV-2 sequences and use them to perform a comprehensive analysis to trace the origins and spread of the virus. We find that travelers returning from the United States of America significantly contributed to viral spread in Israel, more than their proportion in incoming infected travelers. Using phylodynamic analysis, we estimate that the basic reproduction number of the virus was initially around 2.5, dropping by more than two-thirds following the implementation of social distancing measures. We further report high levels of transmission heterogeneity in SARS-CoV-2 spread, with between 2-10% of infected individuals resulting in 80% of secondary infections. Overall, our findings demonstrate the effectiveness of social distancing measures for reducing viral spread.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Imported/virology , Coronavirus Infections/transmission , Genome, Viral/genetics , Pneumonia, Viral/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Basic Reproduction Number/statistics & numerical data , COVID-19 , Child , Child, Preschool , Communicable Diseases, Imported/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Female , Humans , Infant , Infant, Newborn , Israel/epidemiology , Male , Middle Aged , Pandemics/prevention & control , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Psychological Distance , RNA, Viral/genetics , SARS-CoV-2 , Sequence Analysis, RNA , United States , Young Adult
8.
Mol Biol Evol ; 38(2): 575-588, 2021 01 23.
Article in English | MEDLINE | ID: covidwho-799461

ABSTRACT

RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In -ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.


Subject(s)
Mutation , RNA Viruses/genetics , RNA, Viral/genetics , Selection, Genetic , Animals , Codon , DNA Mutational Analysis , Databases, Factual , Evolution, Molecular , Genome, Viral , Humans , Nucleotides , Phylogeny , SARS-CoV-2/genetics
SELECTION OF CITATIONS
SEARCH DETAIL