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- Dyrdak, Robert
(author)
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Molecular epidemiology of acute respiratory virus infections
- 2023
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Doctoral thesis (other academic/artistic)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.
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| 2. |
- Humbert, Marion, et al.
(author)
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Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:12
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Journal article (peer-reviewed)abstract
- Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein–Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination. Copyright © 2023 the Author(s).
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| 3. |
- Waldeck, Mattias, et al.
(author)
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Surveillance of tick-borne encephalitis in emerging risk areas in southern Sweden : a retrospective case finding study
- 2023
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In: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 42:1, s. 13-22
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Journal article (peer-reviewed)abstract
- Tick-borne encephalitis (TBE) is an emerging infection causing CNS infection of various severity. Good knowledge of the incidence in the population and defined risk areas is important in risk communication and vaccination recommendations. The aim of this study was to investigate potential underreporting by retrospectively diagnose TBE among patients with viral CNS infections of unknown etiology in a region with emerging risk areas for TBE, and define variables associated with performed TBE serology at the time of infection. Epidemiological data and microbiological diagnostics of cases with viral CNS infection of unknown etiology treated at departments of infectious diseases and pediatrics in Skåne County during 2000–2012 were investigated. Analyses to evaluate variables associated with performed TBE serology at the time of infection were performed. Retrospective TBE serology was performed on stored blood samples when available. TBE serology was already performed at the time of CNS infection in 193 out of 761 cases. Department, type of clinical manifestation, time period of illness, and whether Borrelia serology had been performed were independent variables associated with having had TBE serology performed or not at the time of illness. Only one of 137 cases, where samples could be retrospectively analyzed for TBE, turned out positive. This study shows a low frequency of TBE sampling among patients with meningoencephalitis in a region with emerging risk for TBE. A higher awareness of TBE as differential diagnosis could contribute to earlier detection of new risk areas and adequate preventive advice to the public.
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