Genomic Evolution of SARS-CoV-2 Virus in Immunocompromised Patient, Ireland (original) (raw)

The biological and clinical significance of emerging SARS-CoV-2 variants

Nature Reviews Genetics

Among the many unprecedented aspects of the SARS-CoV-2 pandemic is the intense virological monitoring that has occurred, with more than two million virus isolates having undergone partial or complete genomic sequencing. Initially, genetic sequencing suggested that SARS-CoV-2 was exceptionally well adapted to humans, spreading rapidly with little evidence for natural selection among circulating viruses. This changed during the later months of 2020, with the first reports of emergent SARS-CoV-2 variants associated with increased transmissibility, disease severity and escape from humoral immunity. In this Review, we create a framework for understanding SARS-COV-2 variants by describing fundamental aspects of SARS-CoV-2 evolution, the structure and function of the SARS-CoV-2 spike protein and the laboratory methods used to characterize spike variants. We then describe the biological properties and epidemiological characteristics of these variants and their associated mutations. Lastly, we describe the types of study required for the research, clinical and public health communities to respond to the new threat posed by emerging SARS-CoV-2 variants. Given the wide public interest in this topic, we provide a box of key points. We also provide a repository of the SARS-CoV-2 variant neutralization data discussed in this Review (Stanford University Coronavirus Antiviral & Resistance Database-Susceptibility Data). SARS-CoV-2 evolution Coronaviruses contain an exonuclease enzyme that reduces their replication error rate by about 15-fold to 20-fold in vitro, resulting in an in vivo viral mutation rate about 10-fold lower than that of influenza 1-3. Nonetheless, they accumulate mutations and generate further diversity through the process of recombination when variants with different mutations infect the same host 4-6. Recombination between different SARS-related coronaviruses is likely to have led to the emergence of SARS-CoV-2 (ref. 7) and, although it can be difficult to detect owing to the similarity of most sequences, recombination is occurring to some extent among circulating SARS-CoV-2 variants 6,8. Additionally, host-mediated RNA editing by APOBeC and ADAr enzymes, as evidenced by the dominance of C to U changes in specific dinucleotide contexts, contributes to SARS-CoV-2 diversity 9,10. Although it had been previously assumed that waning immunity explained the observation that people are commonly reinfected with endemic common-cold coronaviruses 11 , recent studies suggest that antigenic drift also contributes to the lack of long-lasting protection following coronavirus infections 12,13. HCoV-229E and HCoV-OC43 sequences over a 30-year period demonstrate a ladder-like phylogenetic tree topology consistent with the emergence of novel variants sweeping

Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic

Genes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10−3–10−4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolv...

Consequences of Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Genome in Comparison to Other Pathogenic Coronaviruses

2021

Background: Late December 2019, an unknown incidence of Pneumonia was observed among some residents of Wuhan city, China. The disease named coronavirus disease 2019 (COVID-19) and declared as a pandemic by the WHO on the March 11th, 2020 by the World Health Organization (WHO) has resulted to the death of million people across the globe. Prior to the current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), two other outbreaks of coronaviruses namely severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have been experienced within the last few decades. This review looks at the unique characteristics of SARS-CoV-2 to the other coronaviruses (SARS-CoV and MERS-CoV) and its significance(s) in the control strategies including diagnostics. Materials and Methods: Using the keywords “coronavirus mutation”, “nucleotide substitution”, “coronavirus evolution”, “SARS-CoV-2”, “COVID-19” publis...

Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

Biomedicines

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoa...

Genetic drift in the genome of SARS COV‐2 and its global health concern

Journal of Medical Virology, 2021

The outbreak of the current coronavirus disease (COVID-19) occurred in late 2019 and quickly spread all over the world. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to a genetically diverse group that mutates continuously leading to the emergence of multiple variants. Although a few antiviral agents and anti-inflammatory medicines are available, thousands of individuals have passed away due to emergence of new viral variants. Thus, proper surveillance of the SARS-CoV-2 genome is needed for the rapid identification of developing mutations over time, which are of the major concern if they occur specifically in the surface spike proteins of the virus (neutralizing analyte). This article reviews the potential mutations acquired by the SARS-CoV2 since the pandemic began and their xqsignificant impact on the neutralizing efficiency of vaccines and validity of the diagnostic assays.

Viral Population Heterogeneity and Fluctuating Mutational Pattern during a Persistent SARS-CoV-2 Infection in an Immunocompromised Patient

Viruses

Literature offers plenty of cases of immunocompromised patients, who develop chronic and severe SARS-CoV-2 infections. The aim of this study is to provide further insight into SARS-CoV-2 evolutionary dynamic taking into exam a subject suffering from follicular lymphoma, who developed a persistent infection for over 7 months. Eight nasopharyngeal swabs were obtained, and were analyses by qRT-PCR for diagnostic purposes. All of them were considered eligible (Ct < 30) for NGS sequencing. Sequence analysis showed that all sequences matched the B.1.617.2 AY.122 lineage, but they differed by few mutations identifying three genetically similar subpopulations, which evolved during the course of infection, demonstrating that prolonged replication is paralleled with intra-host virus evolution. These evidences support the hypothesis that SARS-CoV-2 adaptive capacities are able to shape a heterogeneous viral population in the context of immunocompromised patients. Spill-over of viral variant...

Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates

Virus Genes, 2005

Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic.

SARS‐CoV ‐2 biology and variants: anticipation of viral evolution and what needs to be done

Environmental Microbiology, 2021

to transmission (viral epidemiology) and disease data (patient clinical data), and the population granularities of these. In this editorial, we explore key facets of viral biology and the influence of relevant aspects of human polymorphisms, human behaviour, geography and climate and, based on this, derive a series of recommendations to monitor viral evolution and predict the types of variants that are likely to arise.

Factors Associated with Emerging and Re-emerging of SARS-CoV-2 Variants

2021

Global spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has triggered unprecedented scientific efforts, as well as containment and treatment measures. Despite these efforts, SARS-CoV-2 infections remain unmanageable in some parts of the world. Due to inherent mutability of RNA viruses, it is not surprising that the SARS-CoV-2 genome has been continuously evolving since its emergence. Recently, four functionally distinct variants, B.1.1.7, B.1.351, P.1 and CAL.20C, have been identified, and they appear to more infectious and transmissible than the original (Wuhan-Hu-1) virus. Here we provide evidence based upon a combination of bioinformatics and structural approaches that can explain the higher infectivity of the new variants. Our results show that the greater infectivity of SARS-CoV-2 than SARS-CoV can be attributed to a combination of several factors, including alternate receptors. Additionally, we show that new SARS-CoV-2 variants emerged in the background o...

Evolution of SARS-CoV-2 variants: a mini-review

African Journal of Clinical and Experimental Microbiology

SARS-CoV-2 has evolved over time with several mutations, especially on the spike protein, which has led to emergence of various variants. With the evolution of SARS-CoV-2 come new challenges in surveillance, effectiveness of preventive and treatment strategies, and outcome of the disease. Despite the lockdowns, mask mandates and other preventive measures put in place, in addition to over 10 million vaccine doses that have been administered globally as of February 2022, COVID-19 cases have risen to over 435 million and resulted in over 5.9 million deaths, largely as a result of the evolution of SARS-CoV-2 variants. To review the evolution of these variants, we searched different online database sources using keywords such as “source of SARS-CoV-2”, “SARS-CoV-2 origin”, “evolution of SARS-CoV-2”, “SARS-CoV-2 variants”, “variants of concern”, “variants of interest”, and “variants of high consequence”. This was to enable us give a good report about the various variants of SARS-CoV-...