scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish Chandra Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z. Li
Keyword(s):  
Amino Acid ◽  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Antibody Treatment ◽  
Systematic Assessment ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Background. Both SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods. A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 to community-driven evolution. Results. Fourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 and N genes. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment. Conclusions. SARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.

scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish C Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z Li
Keyword(s):  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Geographic Region ◽  
Antibody Treatment ◽  
Viral Genomes ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Abstract Background Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

scholarly journals Acquisition and onward transmission of a SARS-CoV-2 E484K variant among household contacts of a bamlanivimab-treated patient

2021 ◽  
Author(s):  
Arick P Sabin ◽  
Craig S Richmond ◽  
Paraic A Kenny
Keyword(s):  
Monoclonal Antibody ◽  
De Novo ◽  
Treated Patient ◽  
Viral Evolution ◽  
Surveillance Program ◽  
Antibody Treatment ◽  
Selective Pressures ◽  
Real Risk ◽  
Monoclonal Antibody Treatment ◽  
Close Contacts

The implementation of monoclonal antibody therapeutics during the COVID19 pandemic has altered the selective pressures encountered by SARS-CoV-2, raising the possibility of selection for variants resistant to one or more monoclonal antibodies and subsequent transmission into the wider population. Early studies indicated that monoclonal antibody treatment in immunocompromised individuals could result in within-host viral evolution preferentially affecting epitopes recognized by these antibodies, although whether this signifies a real risk of transmissible antibody resistant virus is unclear. In this study we have taken advantage of a regional SARS-CoV-2 genomic surveillance program encompassing regions in Wisconsin, Minnesota and Iowa to monitor the introduction or de novo emergence of SARS-Cov-2 lineages with clinically relevant variants. Here we describe a newly acquired E484K mutation in the SARS-CoV-2 spike protein detected within the B.1.311 lineage. Multiple individuals in two related households were infected. The timing and patterns of subsequent spread were consistent with de novo emergence of this E484K variant in the initially affected individual who had been treated with bamlanivimab monotherapy. The subsequent transmission to close contacts occurred several days after the resolution of symptoms and the end of this patient's quarantine period. Our study suggest that the selective pressures introduced by the now widespread administration of these antibodies may warrant increased genomic surveillance to identify and mitigate spread of therapy-induced variants.

scholarly journals Phylogenetic Analysis: Basic Concepts and Its Use as a Tool for Virology and Molecular Epidemiology

2018 ◽  
Vol 44 (1) ◽  
pp. 20
Author(s):  
Eloiza Teles Caldart ◽  
Helena Mata ◽  
Cláudio Wageck Canal ◽  
Ana Paula Ravazzolo
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Molecular Epidemiology ◽  
Phylogenetic Analyses ◽  
Phylogenetic Reconstruction ◽  
Evolutionary Process ◽  
Amino Acid Sequences ◽  
Evolutionary Models ◽  
Reconstruction Methods ◽  
Basic Concepts

Background: Phylogenetic analyses are an essential part in the exploratory assessment of nucleic acid and amino acid sequences. Particularly in virology, they are able to delineate the evolution and epidemiology of disease etiologic agents and/or the evolutionary path of their hosts. The objective of this review is to help researchers who want to use phylogenetic analyses as a tool in virology and molecular epidemiology studies, presenting the most commonly used methodologies, describing the importance of the different techniques, their peculiar vocabulary and some examples of their use in virology.Review: This article starts presenting basic concepts of molecular epidemiology and molecular evolution, emphasizing their relevance in the context of viral infectious diseases. It presents a session on the vocabulary relevant to the subject, bringing readers to a minimum level of knowledge needed throughout this literature review. Within its main subject, the text explains what a molecular phylogenetic analysis is, starting from a multiple alignment of nucleotide or amino acid sequences. The different software used to perform multiple alignments may apply different algorithms. To build a phylogeny based on amino acid or nucleotide sequences it is necessary to produce a data matrix based on a model for nucleotide or amino acid replacement, also called evolutionary model. There are a number of evolutionary models available, varying in complexity according to the number of parameters (transition, transversion, GC content, nucleotide position in the codon, among others). Some papers presented herein provide techniques that can be used to choose evolutionary models. After the model is chosen, the next step is to opt for a phylogenetic reconstruction method that best fits the available data and the selected model. Here we present the most common reconstruction methods currently used, describing their principles, advantages and disadvantages. Distance methods, for example, are simpler and faster, however, they do not provide reliable estimations when the sequences are highly divergent. The accuracy of the analysis with probabilistic models (neighbour joining, maximum likelihood and bayesian inference) strongly depends on the adherence of the actual data to the chosen development model. Finally, we also explore topology confidence tests, especially the most used one, the bootstrap. To assist the reader, this review presents figures to explain specific situations discussed in the text and numerous examples of previously published scientific articles in virology that demonstrate the importance of the techniques discussed herein, as well as their judicious use.Conclusion: The DNA sequence is not only a record of phylogeny and divergence times, but also keeps signs of how the evolutionary process has shaped its history and also the elapsed time in the evolutionary process of the population. Analyses of genomic sequences by molecular phylogeny have demonstrated a broad spectrum of applications. It is important to note that for the different available data and different purposes of phylogenies, reconstruction methods and evolutionary models should be wisely chosen. This review provides theoretical basis for the choice of evolutionary models and phylogenetic reconstruction methods best suited to each situation. In addition, it presents examples of diverse applications of molecular phylogeny in virology.

scholarly journals Use of a Unique Mobile Medical Asset in COVID Monoclonal Antibody Treatment

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 990
Author(s):  
Herman Morchel ◽  
David Clark ◽  
Leighanne Buenvenida ◽  
Chinwe Ogedegbe
Keyword(s):  
Emergency Department ◽  
Monoclonal Antibody ◽  
Patient Care ◽  
Emergency Care ◽  
Environmental Changes ◽  
Physical Space ◽  
Antibody Treatment ◽  
Monoclonal Antibody Treatment ◽  
Mobile Satellite ◽  
Novel Coronavirus

The COVID-19 pandemic and the subsequent surge of patients presented to emergency departments has forever changed the paradigm of delivering emergency care. The highly infectious nature of the 2019 Novel Coronavirus, or COVID-19, mandated strict environmental changes, novel patient care, and flexible strategies to continue to deliver efficient emergency care while maintaining appropriate physical distancing between suspect and non-suspect COVID-19 patients. The engagement of a unique rapidly deployable Mobile Satellite Emergency Department (MSED) with scalable capability from prompt care to resuscitation level allowed the emergency care team to optimize patient care and throughput. The MSED was strategically located adjacent to the ambulance entrance. While initially deployed to increase Emergency Department surge capacity, the MSED was repurposed to cohort and treat COVID patients with the monoclonal antibody, Bamlanivimab, who were expected to be discharged after treatment. This allowed for more efficient use of Emergency Department resources, including physical space and staffing.

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