Recurrent SARS-CoV-2 mutations in immunodeficient patients.

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations that aid cell-cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

The SARS-CoV-2 variants around us: A literature review

The SARS-CoV-2 outbreak in Wuhan (China) has become a global pandemic. Various variants of SARS-CoV-2 have been detected and the variant number of the virus continues to grow. A particular SARS-CoV-2 variant can be detected in a country that was never infected before by the virus. Furthermore, a specific SARS-CoV-2 variant, which has been detected before in a country, can be detected too in another country. The emergence of SARS-CoV-2 variants is mainly caused by mutations and recombinations. The emergence of a SARS-CoV-2 variant in a country (which was never infected before by the virus), of course, can be explained easily as it is caused by the effect of the viral spread among countries, although there may be another explanation. On the other hand, the emergence of a SARS-CoV-2 variant (which has been previously detected in a country) in another country, always has been explained only as it is caused by the effect of the viral spread between countries. However, maybe it is caused by another factor. A literature review was performed to look for the explanation related to the emergence of a certain SARS-Cov-2 variant (which is already detected before in another country) in a country. Based on the literature review results related to the RNA virus genome and its mutation as well as its recombination, it is easy to explain the cause/agent of the emergence of a SARS-CoV-2 variant (which has been previously detected elsewhere) in another country. In this case, the emergence of a SARS-CoV-2 variant (which has been previously detected elsewhere) in a country may be caused by mutations and/or recombinations in addition to the probability that it may also occur due to the spread of the virus among countries;so the emergence of SARS-CoV-2 variant that has been previously detected elsewhere in other countries does not only occur due to the spread of the virus. © 2023,Malaysian Journal of Microbiology. All Rights Reserved.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: A multi-model study.

Background: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5-11 years on COVID-19 burden and resilience against variant strains. Methods: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5-11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. Findings: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5-11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. Interpretation: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5-11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Funding: Various (see acknowledgments).

Are there medium to short-term multifaceted effects of the airborne pollutant PM2.5 determining the emergence of SARS-CoV-2 variants?

The COVID-19 pandemic has been characterised by successiveoutbreaks effecting large swathes of the world's populations. These waves of infection have been mainly driven by a number of more transmissiblevariants which appear to evade the populations' immunity gained from previous outbreaks. There appears to be a link between COVID-19 and a ubiquitous airborne pollutant calledparticulate matter, PM2.5. Particulate matter through a number of mechanisms, including its anthropogenic effect, appears to be associated with the incidence and the mortality related to the COVID-19 pandemic. This paper poses a number of hypotheses on the short to medium-term mechanisms whereby PM2.5 may be party to the natural selection of SARS-CoV-2 virus, with the consequent emergence of variants.