SARS-CoV-2 presented moderately during two episodes of the infection with lack of antibody responses (original) (raw)

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...

Mutations and Epidemiology of SARS-CoV-2 Compared to Selected Corona Viruses during the First Six Months of the COVID-19 Pandemic: A Review

Journal of Pure and Applied Microbiology, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus (CoV) disease 2019 (COVID-19). This study compared the genome, mutations, and infectivity/ transmissibility of SARS-CoV-2 with selected betacoronaviruses (beta-CoVs). This study further examined the origin, risk factors, and outbreaks caused by beta-CoVs. We searched the following databases for relevant studies: PubMed, Google Scholar, and the World Health Organization COVID-19 database. A close relationship between SARS-CoV-2 and SARS bat-like CoV RaTG13 (98.9%) was found at the amino acid level, followed by pangolin CoVs. Non-synonymous mutations occur at high frequencies in the open reading frame (ORF) 1ab, spike (S) protein, and nucleocapsid. Mutations P323L and D614G in the RNA-dependent RNA polymerase (RdRp) and S protein, respectively, occur at a high frequency globally. Mutations at position 3037 in the nonstructural protein (Nsp) 3, 14408 (RdRp), and 23403 (S) confer transmissibility to SARS-CoV-2. SARS-CoV-2 has higher infectivity and transmissibility than SARS-CoV, which shares the same receptor. Although bats are confirmed reservoirs, intermediate hosts are currently unknown. Smoking, old age, diabetes, cardiovascular diseases, and hypertension have all been associated with COVID-19. Within six months of its outbreak, COVID-19 was reported in all countries worldwide, whereas SARS was reported in 28 countries and Middle East respiratory syndrome (MERS) in 5 countries. However, the fatality rate of MERS (65%) was higher than that of COVID-19 (4.9%) and SARS (6.6%). Identifying the SARS-CoV-2 intermediate hosts will help prevent future outbreaks. Attention should be given to the pangolin CoVs. Variations in the S gene may confer transmissibility and infectivity.

Rapid System to Detect Variants of SARS-CoV-2 in Nasopharyngeal Swabs

Viruses

Currently, the reference method for identifying the presence of variants of SARS-CoV-2 is whole genome sequencing. Although it is less expensive than in the past, it is still time-consuming, and interpreting the results is difficult, requiring staff with specific skills who are not always available in diagnostic laboratories. The test presented in this study aimed to detect, using traditional real-time PCR, the presence of the main variants described for the spike protein of the SARS-CoV-2 genome. The primers and probes were designed to detect the main deletions that characterize the different variants. The amplification targets were deletions in the S gene: 25–27, 69–70, 241–243, and 157–158. In the ORF1a gene, the deletion 3675–3677 was chosen. Some of these mutations can be considered specific variants, while others can be identified by the simultaneous presence of one or more deletions. We avoided using point mutations in order to improve the speed of the test. Our test can help...

Notable and Emerging Variants of SARS-CoV-2 Virus: A Quick Glance

Indian Journal of Clinical Biochemistry

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a highly contagious pathogenic coronavirus to emerge and spread in human populations. Although substantial exertions have been laid to avert spread of COVID-19 by therapeutic and preventive countermeasures, but emergence of SARS-CoV-2 variants as a result of mutations make the infection more ominous. New viral confers a higher nasopharyngeal viral load, increased viral transmissibility, higher infectiousness, immune escape, increased resistance to monoclonal/polyclonal antibodies from convalescence sera/vaccine, and an enhanced virulence. Thus, it is pertinent to monitor evolving mutations and genetic diversity of SARS-CoV-2 as it is decisive for understanding the viral variants. In this review we provide an overview of colloquial nomenclature and the genetic characteristics of different SARS-CoV-2 variants in the context of mutational changes of the circulating strains, transmissibility potential, virulence and infectivity.

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

Emergence of SARS-CoV-2 New Variants and Their Clinical Significance

Canadian Journal of Infectious Diseases and Medical Microbiology

COVID-19 is a respiration-related disease caused by SARS-CoV-2 and was identified in China’s Wuhan city. More than 223 countries are affected by the disease worldwide. The new variants of the COVID-19 virus are causing problems, from average to life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Presently, there are 170 vaccine candidates, out of which 10 have been approved by the WHO for vaccination, such as Ad26.COV2.S, Pfizer/BioNTech, COVISHIELD, Covovax, Moderna, KoviVac, and some other vaccines to combat the deadly SARS-CoV-2 infection. From all these vaccines, Pfizer/BioNTech and Moderna are showing the highest efficacy against COVID-19. These vaccines are highly efficient against COVID-19 disease, but their potentiality against new variants remains a question. COVID-19 vaccines are highly effective at preventing severe illnesses, hospitalizations, and death. The antibodies elicited by earlier infection or vaccination are the key for possible protection...

Novel and emerging mutations of SARS-CoV-2: Biomedical implications

Biomedicine & Pharmacotherapy, 2021

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 virus strains has geographical diversity associated with diverse severity, mortality rate, and response to treatment that were characterized using phylogenetic network analysis of SARS-CoV-2 genomes. Although, there is no explicit and integrative explanation for these variations, the genetic arrangement, and stability of SARS-CoV-2 are basic contributing factors to its virulence and pathogenesis. Hence, understanding these features can be used to predict the future transmission dynamics of SARS-CoV-2 infection, drug development, and vaccine. In this review, we discuss the most recent findings on the mutations in the SARS-CoV-2, which provide valuable information on the genetic diversity of SARS-CoV-2, especially for DNA-based diagnosis, antivirals, and vaccine development for COVID-19.

SARS-Cov-2 Variants and Current Status

COVID-19 virus, SARS-CoV-2 first reported from Wuhan City of Hubei Province of China became pandemic infectious disease of severe respiratory disorder. Globally 17.8 Cr population was effected within a short span of period leading to 38.6 L deaths. Coronoviruses are large enveloped RNA viruses of Coronaviridae. Coronavirus employs a complex gene expression and pathway system unique among RNA viruses. SARA-CoV-2 is reported to mutate and variants reported to have one specific mutation, D614G which is makes to spread faster. WHO is monitoring and assessing the evolution of SARS-CoV-2 and notified Variants of Concern (VOCs) and Variants of Interest (VOIs), in order to prioritise the activities globally on containing COVID-19 pandemic. Currently genetic lineages by GISAID, Nextstrain and Pango are in use to code variants detected and being labeled using letters of the Greek Alphabet, i.e., Alpha, Beta, Gamma and Delta etc. Presently 15 vaccines were developed based on the SARS-CoV-2 spike protein, of original Wuhan-hu-1 and being administered in different countries. Surveillance and monitoring of the genomic sequence of SARS-CoV-2 is being done on a priority as virus is mutating for development of effective vaccine or therapeutic measures. Only 0.8% of people in low-income countries have received a single dose out of 20.8% of the world population which is a big concern for vulnerable groups.

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.