Comparative genomic analysis demonstrates that true reinfection following SARS-CoV-2 infection is possible (original) (raw)
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Frontiers in Cellular and Infection Microbiology
Large-scale SARS-CoV-2 molecular testing coupled with whole genome sequencing in the diagnostic laboratories is instrumental for real-time genomic surveillance. The extensive genomic, laboratory, and clinical data provide a valuable resource for understanding cases of reinfection versus prolonged RNA shedding and protracted infections. In this study, data from a total of 22,292 clinical specimens, positive by SARS-CoV-2 molecular diagnosis at Johns Hopkins clinical virology laboratory between March 11th 2020 to September 23rd 2021, were used to identify patients with two or more positive results. A total of 3,650 samples collected from 1,529 patients who had between 2 and 20 positive results were identified in a time frame that extended up to 403 days from the first positive. Cycle threshold values (Ct) were available for 1,622 samples, the median of which was over 30 by 11 days after the first positive. Extended recovery of infectious virus on cell culture was notable for up to 70 ...
Journal of Medical Virology, 2021
To date, a large number of case reports have emerged claiming COVID-19 reinfection, some confirmed by the distinct viral genotypes in each episode. 1-9 This communication highlights a case report from Delhi, India, with two instances of SARS-CoV-2 where the second episode witness moderate illness after 73 days of the first SARS-CoV-2 positive episode (asymptomatic). A 52-year-old male individual was tested positive at a COVID health care unit [RT-PCR/ Ct-values (ORF1ab-36.04/E gene-36.74)-using Roche Cobas 6800] for SARS-COV-2 on June 12, 2020, upon contact tracing. At that
Frontiers in Medicine, 2021
Background: SARS-CoV-2 infection may not provide long lasting post-infection immunity. While hundreds of reinfections have reported only a few have been confirmed. Whole genome sequencing (WGS) of the viral isolates from the different episodes is mandatory to establish reinfection.Methods: Nasopharyngeal (NP), oropharyngeal (OP) and whole blood (WB) samples were collected from paired samples of four individuals who were suspected of SARS-CoV-2 reinfection based on distinct clinical episodes and RT-PCR tests. Details from their case record files and investigations were documented. RNA was extracted from the NP and OP samples and subjected to WGS, and the nucleotide and amino acid sequences were subjected to genome and protein-based functional annotation analyses. Serial serology was performed for Anti-N IgG, Anti- S1 RBD IgG, and sVNT (surrogate virus neutralizing test).Findings: Three patients were more symptomatic with lower Ct values and longer duration of illness. Seroconversion ...
SARS-COV-2: Insight Into the Emerging Genetic Variants
PROBLEMS of Infectious and Parasitic Diseases, 2022
SARS-CoV-2 is a highly contagious virus, which appeared in China in late 2019, spread rapidly and caused the largest pandemic in the last 100 years. Despite the intensive research, there is no specific antiviral drug currently. Effective vaccines have been developed in a short time and they are already widely used. As a RNA virus, SARS-CoV-2 mutates constantly, and several thousand genetic variants have emerged in the course of the pandemic, some of which are associated with increased infectivity, reinfection risk, reduced activity of therapeutic antibodies and reduced effectiveness of vaccines. This review highlights the features in SARS-CoV-2 structure and replication cycle that would help to understand the significance of individual mutations contained in the emerging genetic variants and to predict the impact of mutations on viral transmissibility, disease severity, diagnostics, therapeutics or immune escape. The main characteristics of the variants of concern are presented.
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
Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center
BackgroundIncreased reinfection rates with SARS-CoV-2 have recently been reported, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection.MethodsWe identified cases where patients had two positive tests for SARS-CoV-2 and evaluated which of these had been sequenced as part of our surveillance efforts, and evaluated sequencing and clinical data.Results750 patients (920 samples) had a positive test at least 90 days after the initial test. The median time between tests was 377 days, and 724 (79%) of the post 90-day positives were collected after the emergence of the Omicron variant in November 2021. Sequencing was attempted on 231 samples and successful in 127. Successful sequencing spiked during the Omicron surge and showed higher median days from initial infection compared to failed sequences (median 398 days compared to 276 days, p<0.0005). A total of 122 (98%) patients showed evidence of reinfection, 45 of which had sequence...
Genomic evidence of SARS-CoV-2 reinfection case with the emerging B.1.2 variant in Brazil
Journal of Infection, 2021
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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...
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.