Molecular epidemiology of acute respiratory virus infections
Author: Dyrdak, Robert
Date: 2023-06-02
Location: Rolf Luft auditorium, L1:00, Karolinska University Hospital, Solna
Time: 09.00
Department: Inst för mikrobiologi, tumör- och cellbiologi / Dept of Microbiology, Tumor and Cell Biology
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Thesis (1.367Mb)
Abstract
Acute respiratory virus infections are very common but can also cause severe disease. In my thesis, I have analysed the molecular epidemiology of acute respiratory virus infections caused by enterovirus D68 and coronaviruses.
In Paper I, we used real-time PCR and Sanger sequencing to analyse the outbreak of enterovirus D68 in Stockholm in 2016. We found that the outbreak was caused by the subclade B3, and we also described three patients with neurological manifestations. The virus sequences were closely related to concurrent sequences from North America.
In Paper II, we developed an assay for whole-genome sequencing of enterovirus D68 a next-generation platform. By using the assay on the samples from the 2016 outbreak, we found that the outbreak was caused by multiple independent introductions of the virus. We also estimated the time to the most common recent ancestor for the subclades B1 and B3 to 2009.
In Paper III, we used the whole-genome sequencing assay in a European multicentre study of enterovirus D68 circulation in the 2018 season. We also included sequences in public repositories. We found that the viruses in 2018 belonged to subclades A2 and B3 and that sequences in subclade B3 originated from the circulation in 2016. We also found that enterovirus D68 had a rapid geographic mixing and that residues on the surface of the virus particle had an elevated substitution rate of amino acids. Hence, we proposed asymptomatic reinfections of adults to explain both rapid geographical dispersal and selective pressure on the surface residues.
In Paper IV, we analysed stored results from routine clinical diagnostics for the four common cold coronaviruses. The data contained the results from September 2009 to April 2020. At the species level, we found a pattern of alternating biennial circulation, and we also found the circulation of Betacoronaviruses to peak earlier than that of Alphacoronaviruses.
In Paper V, we investigated Sweden’s first SARS-CoV-2 pandemic wave in 2020. We analysed stored respiratory samples with real-time PCR for SARS-CoV-2 and found that community transmissions started earlier than previously appreciated. We also se-quenced stored SARS-CoV-2-positive samples. To these sequences, we added infor-mation from contact tracing records and combined them with data from public reposi-tories. Among cases exposed abroad, we mainly found clades 20B and 20A, whereas clade 20C dominated domestic infections. Furthermore, we found the proportion of clade 20C to be correlated with the cumulative number of deaths due to COVID-19. We interpreted this as early undetected introductions of clade 20C having had a significant impact on the further course of the pandemic in Sweden.
In Paper I, we used real-time PCR and Sanger sequencing to analyse the outbreak of enterovirus D68 in Stockholm in 2016. We found that the outbreak was caused by the subclade B3, and we also described three patients with neurological manifestations. The virus sequences were closely related to concurrent sequences from North America.
In Paper II, we developed an assay for whole-genome sequencing of enterovirus D68 a next-generation platform. By using the assay on the samples from the 2016 outbreak, we found that the outbreak was caused by multiple independent introductions of the virus. We also estimated the time to the most common recent ancestor for the subclades B1 and B3 to 2009.
In Paper III, we used the whole-genome sequencing assay in a European multicentre study of enterovirus D68 circulation in the 2018 season. We also included sequences in public repositories. We found that the viruses in 2018 belonged to subclades A2 and B3 and that sequences in subclade B3 originated from the circulation in 2016. We also found that enterovirus D68 had a rapid geographic mixing and that residues on the surface of the virus particle had an elevated substitution rate of amino acids. Hence, we proposed asymptomatic reinfections of adults to explain both rapid geographical dispersal and selective pressure on the surface residues.
In Paper IV, we analysed stored results from routine clinical diagnostics for the four common cold coronaviruses. The data contained the results from September 2009 to April 2020. At the species level, we found a pattern of alternating biennial circulation, and we also found the circulation of Betacoronaviruses to peak earlier than that of Alphacoronaviruses.
In Paper V, we investigated Sweden’s first SARS-CoV-2 pandemic wave in 2020. We analysed stored respiratory samples with real-time PCR for SARS-CoV-2 and found that community transmissions started earlier than previously appreciated. We also se-quenced stored SARS-CoV-2-positive samples. To these sequences, we added infor-mation from contact tracing records and combined them with data from public reposi-tories. Among cases exposed abroad, we mainly found clades 20B and 20A, whereas clade 20C dominated domestic infections. Furthermore, we found the proportion of clade 20C to be correlated with the cumulative number of deaths due to COVID-19. We interpreted this as early undetected introductions of clade 20C having had a significant impact on the further course of the pandemic in Sweden.
List of papers:
I. Dyrdak R, Grabbe M, Hammas B, Ekwall J, Hansson KE, Luthander J, Naucler P, Reinius H, Rotzén-Östlund M, Albert J. Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. Eurosurveillance. 2016 Nov 17;21(46):30403.
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II. Dyrdak R, Mastafa M, Hodcroft EB, Neher RA, Albert J. Intra- and interpatient evolution of enterovirus D68 analysed by whole-genome deep sequencing. Virus Evolution. 2019 Apr 24;5(1):vez007.
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III. Hodcroft EB, Dyrdak R, Andrés C, Egli A, Reist J, García Martínez de Artola D, Alcoba-Flórez J, Niesters HGM, Antón A, Poelman R, Reynders M, Wollants E, Neher RA, Albert J. Evolution, geographic spreading, and demographic distribution of Enterovirus D68. PLoS Pathogen. 2022 May 31;18(5):e1010515.
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IV. Dyrdak R, Hodcroft EB, Wahlund M, Neher RA, Albert J. Interactions between seasonal human coronaviruses and implications for the SARS-CoV-2 pandemic: A retrospective study in Stockholm, Sweden, 2009-2020. Journal of Clinical Virology. 2021 Mar;136:104754.
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V. Dyrdak R, Hodcroft EB, Grabbe M, Franklin H, Gisslén M, Lindh M, Nederby-Öhd J, Ringlander J, Sundqvist M, Neher RA, Albert J. Early unrecognised SARS-CoV-2 introductions shaped the first pandemic wave in Sweden. [Manuscript]
I. Dyrdak R, Grabbe M, Hammas B, Ekwall J, Hansson KE, Luthander J, Naucler P, Reinius H, Rotzén-Östlund M, Albert J. Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. Eurosurveillance. 2016 Nov 17;21(46):30403.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Dyrdak R, Mastafa M, Hodcroft EB, Neher RA, Albert J. Intra- and interpatient evolution of enterovirus D68 analysed by whole-genome deep sequencing. Virus Evolution. 2019 Apr 24;5(1):vez007.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Hodcroft EB, Dyrdak R, Andrés C, Egli A, Reist J, García Martínez de Artola D, Alcoba-Flórez J, Niesters HGM, Antón A, Poelman R, Reynders M, Wollants E, Neher RA, Albert J. Evolution, geographic spreading, and demographic distribution of Enterovirus D68. PLoS Pathogen. 2022 May 31;18(5):e1010515.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Dyrdak R, Hodcroft EB, Wahlund M, Neher RA, Albert J. Interactions between seasonal human coronaviruses and implications for the SARS-CoV-2 pandemic: A retrospective study in Stockholm, Sweden, 2009-2020. Journal of Clinical Virology. 2021 Mar;136:104754.
Fulltext (DOI)
Pubmed
View record in Web of Science®
V. Dyrdak R, Hodcroft EB, Grabbe M, Franklin H, Gisslén M, Lindh M, Nederby-Öhd J, Ringlander J, Sundqvist M, Neher RA, Albert J. Early unrecognised SARS-CoV-2 introductions shaped the first pandemic wave in Sweden. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Albert, Jan
Co-supervisor: Neher, Richard A; Blom, Kim; Björkström, Niklas K
Issue date: 2023-05-10
Rights:
Publication year: 2023
ISBN: 978-91-8016-988-2
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