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 patients 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.
ABSTRACT
The SARS-Coronavirus-2 (SARS-CoV-2) driven pandemic was first recognized in late 2019, and the first few months of its evolution were relatively clock-like, dominated mostly by neutral substitutions. In contrast, the second year of the pandemic was punctuated by the emergence of several variants that bore evidence of dramatic evolution. Here, we compare and contrast evolutionary patterns of various variants, with a focus on the recent Delta variant. Most variants are characterized by long branches leading to their emergence, with an excess of non-synonymous substitutions occurring particularly in the Spike and Nucleocapsid proteins. In contrast, the Delta variant that is now becoming globally dominant, lacks the signature long branch, and is characterized by a step-wise evolutionary process that is ongoing. Contrary to the "star-like" topologies of other variants, we note the formation of several distinct clades within Delta that we denote as clades A-E. We find that sequences from the Delta D clade are dramatically increasing in frequency across different regions of the globe. Delta D is characterized by an excess of non-synonymous mutations, mostly occurring in ORF1a/b, some of which occurred in parallel in other notable variants. We conclude that the Delta surge these days is composed almost exclusively of Delta D, and discuss whether selection or random genetic drift has driven the emergence of Delta D.
ABSTRACT
The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. We performed a case-control study that examined the distribution of SARS-CoV-2 variants observed in infections of vaccinated individuals ("breakthrough cases") and matched infections of unvaccinated individuals. We hypothesized that if there is lower vaccine effectiveness against one of the VOCs, its proportion among the breakthrough cases should be higher than among unvaccinated cases. Our results show that vaccinees that tested positive at least a week after the second dose were indeed disproportionally infected with B.1.351, as compared with unvaccinated individuals (odds ratio of 8:1). Those who tested positive between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs at particular time windows following vaccination. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high among those fully vaccinated. These results overall suggest that vaccine breakthrough infection may be more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.
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 sequenced 212 SARS-CoV-2 sequences and use them to perform a comprehensive analysis to trace the origins and spread of the virus. A phylogenetic analysis including thousands of globally sampled sequences allowed us to infer multiple independent introductions into Israel, followed by local transmission. Returning travelers from the U.S. contributed dramatically more to viral spread relative to their proportion in incoming infected travelers. Using phylodynamic analysis, we estimated that the basic reproduction number of the virus was initially around ~2.0-2.6, dropping by two-thirds following the implementation of social distancing measures. A comparison between reported and model-estimated case numbers indicated high levels of transmission heterogeneity in SARS-CoV-2 spread, with between 1-10% of infected individuals resulting in 80% of secondary infections. Overall, our findings underscore the ability of this virus to efficiently transmit between and within countries, as well as demonstrate the effectiveness of social distancing measures for reducing its spread.