COVID-19 in an immunocompromised host: persistent shedding of viable SARS-CoV-2 and emergence of multiple mutations: a case report

Leung, Wayne; Chorlton, Samuel D; Tyson, John R.; Al‐Rawahi, Ghada N.; Jassem, Agatha N; Prystajecky, Natalie; Masud, Shazia; Deans, Gregory D.; Chapman, Michael; Mirzanejad, Yazdan; Murray, Melanie; Wong, Patrick

doi:10.1016/j.ijid.2021.10.045

Cited by 51 publications

(48 citation statements)

References 14 publications

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“…Immunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been implicated in the emergence of highly mutated SARS-CoV-2 variants ( 1 – 12 ). Unlike immunocompetent hosts, patients with compromised immunity from underlying medical conditions or immunosuppressive therapies have been reported to have high SARS-CoV-2 burdens for protracted periods ( 1 , 3 , 7 , 9 – 11 , 13 ).…”

Section: Observationmentioning

confidence: 99%

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts

Yingtaweesittikul

Tan

et al. 2022

Microbiol Spectr

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The emergence of clinically important mutations described in this report highlights the need for sustained vigilance and containment measures when managing immunocompromised patients with persistent COVID-19. Even as jurisdictions across the globe start lifting pandemic control measures, immunocompromised patients with persistent COVID-19 constitute a unique group that requires close genomic monitoring and enhanced infection control measures, to ensure early detection and containment of mutations and variants of therapeutic and public health importance.

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Section: Observationmentioning

confidence: 99%

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts

Yingtaweesittikul

Tan

et al. 2022

Microbiol Spectr

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“…Now virus load decreases exponentially until the virus becomes eliminated about 10-30 days after initial infection Ke et al, 2021). In some immunocompromised individuals, viral clearance can take many weeks (Choi et al, 2020;Leung et al, 2022). However, some argue that the isolation of infectious virus is rare after 20 days post-infection (van Kampen et al, 2021).…”

Section: Description Of the Modelmentioning

confidence: 99%

Evolutionary safety of death by mutagenesis

Lobinska

Pilpel

Nowak

2022

Preprint

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Nucleoside analogs are a major class of antiviral drugs. Some act by increasing the viral mutation rate causing “death by mutagenesis” of the virus. Their mutagenic capacity, however, may lead to an evolutionary safety concern. We define evolutionary safety as a probabilistic assurance that the treatment will not generate an increased number of epidemiologically concerning mutated virus progeny. We develop a mathematical framework to estimate the total mutant load produced with and without mutagenic treatment. We predict rates of appearance of virus mutants as a function of the timing of treatment and the immune competence of patients, employing various assumptions about the vulnerability of the viral genome and its potential to generate undesired phenotypes. We focus on the case study of Molnupiravir, which is an FDA-approved treatment against COVID-19. We estimate that Molnupiravir is narrowly evolutionarily safe, subject to the current estimate of parameters. Evolutionary safety can be improved by restricting treatment to individuals with a low clearance rate and by designing treatments that lead to a greater increase in mutation rate. We report a simple rule to determine the fold-increase in mutation rate required to obtain evolutionary safety which is also applicable to other pathogen-treatment combinations.

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“…Potential factors that may contribute to the development of long COVID include aberrant immune responses, persistent viral replication, redox imbalance, formation of fibrinolysis-resistant amyloid fibrin microclots, and consequences from acute SARS-CoV-2 injury to one or multiple organs. [8][9][10][11][12][13][14][15][16][17] At present, there is no specific treatment for long COVID and there is a great necessity to garner a better understanding of long COVID subtypes.…”

Section: Introductionmentioning

confidence: 99%

Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs

Reese

Blau

Bergquist

et al. 2022

Preprint

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Accurate stratification of patients with Post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies and could enable more focussed investigation of the molecular pathogenetic mechanisms of this disease. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling long COVID phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Using unsupervised machine learning (k-means clustering), we found six distinct clusters of long COVID patients, each with distinct profiles of phenotypic abnormalities with enrichments in pulmonary, cardiovascular, neuropsychiatric, and constitutional symptoms such as fatigue and fever. There was a highly significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. We show that the clusters we identified in one hospital system were generalizable across different hospital systems. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on long COVID.

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COVID-19 in an immunocompromised host: persistent shedding of viable SARS-CoV-2 and emergence of multiple mutations: a case report

Cited by 51 publications

References 14 publications

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts

Evolutionary safety of death by mutagenesis

Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs

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