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2. Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to recipients’ variants.

Author

Khawaja, T., Kajova, M., Levonen, I., Pietilä, J. P., Välimaa, H., Paajanen, J., Pakkanen, S. H., Patjas, A., Montonen, R., Miettinen, S., Virtanen, J., Smura, T., Sironen, T., Fagerlund, R., Ugurlu, H., Iheozor-Ejiofor, R., Saksela, K., Vahlberg, T., Ranki, A., and Vierikko, A.

Subjects
CONVALESCENT plasma, COVID-19, COVID-19 treatment, ANTIBODY titer, IMMUNOGLOBULINS
Abstract

Introduction: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP. Methods: We recruited hospitalised COVID-19 patients within 10 days of symptom onset and, employing a double-blinded approach, randomised them to receive 200 ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a pre-planned ad hoc analysis, the patients were regrouped by infused CP’s NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP). Results: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p = 0.077). Discussion: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous – recipients’ variant-specific – CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors

Author

Vuorinen, V., Aarnio, M., Alava, M., Alopaeus, Ville, Atanasova, N., Auvinen, M., Balasubramanian, N., Bordbar, H., Erästö, P., Grande, R., Hayward, N., Hellsten, A., Hostikka, S., Hokkanen, J., Kaario, O., Karvinen, A., Kivistö, I., Korhonen, M., Kosonen, R., Kuusela, J., Lestinen, S., Laurila, E., Nieminen, H. J., Peltonen, P., Pokki, J., Puisto, A., Råback, P., Salmenjoki, H., Sironen, T., Österberg, M., Vuorinen, V., Aarnio, M., Alava, M., Alopaeus, Ville, Atanasova, N., Auvinen, M., Balasubramanian, N., Bordbar, H., Erästö, P., Grande, R., Hayward, N., Hellsten, A., Hostikka, S., Hokkanen, J., Kaario, O., Karvinen, A., Kivistö, I., Korhonen, M., Kosonen, R., Kuusela, J., Lestinen, S., Laurila, E., Nieminen, H. J., Peltonen, P., Pokki, J., Puisto, A., Råback, P., Salmenjoki, H., Sironen, T., and Österberg, M.

Abstract

We provide research findings on the physics of aerosol and droplet dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2 during the current pandemic. We utilize physics-based modeling at different levels of complexity, along with previous literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets (d⩽20μm) allows lingering in the air for O(1h) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes O(100μm), into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the individuals, who have been tested positive on COVID-19, could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. O(100). By 3D scale-resolving computational fluid dynamics (CFD) simulations, we give various examples on the transport and dilution of aerosols (d⩽20μm) over distances O(10m) in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modelling. The developed model takes into account the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, ’exposure time’ to virus containing aerosols is proposed to complement the traditional ’safety distance’ thinking. We show that the exposure time to inhale O(100) aerosols could range from O(1s) to O(1min) or even to O(1h) depending on the situation. The Monte-Carlo simulations, along with the theory, provide clear quantitative insight to the exposure time in different public indoor environments., Cited By :11; Export Date: 7 December 2020; Article

Published
2020
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10. Fatal Puumala hantavirus disease:involvement of complement activation and vascular leakage in the pathobiology

Author

Sironen, T. (Tarja), Sane, J. (Jussi), Lokki, M.-L. (Marja-Liisa), Meri, S. (Seppo), Andersson, L. C. (Leif C.), Hautala, T. (Timo), Kauma, H. (Heikki), Vuorinen, S. (Sakari), Rasmuson, J. (Johan), Evander, M. (Magnus), Ahlm, C. (Clas), and Vaheri, A. (Antti)

Subjects
complement activation, case fatality rate, animal diseases, viruses, virus diseases, puumala virus, hantavirus, respiratory tract diseases
Abstract

The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood, and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.

Published
2017

11. Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose blood in Finland

Author

KORHONEN, E. M., PÉREZ VERA, C., PULLIAINEN, A.T., SIRONEN, T., AALTONEN, K., KORTET, R., HÄRKÖNEN, L., HÄRKÖNEN, S., PAAKKONEN, T., NIEMINEN, P., MUSTONEN, A-M, YLÖNEN, H., VAPALAHTI, O., KORHONEN, E. M., PÉREZ VERA, C., PULLIAINEN, A.T., SIRONEN, T., AALTONEN, K., KORTET, R., HÄRKÖNEN, L., HÄRKÖNEN, S., PAAKKONEN, T., NIEMINEN, P., MUSTONEN, A-M, YLÖNEN, H., and VAPALAHTI, O.

Abstract

The deer ked (Lipoptena cervi) is a haematophagous ectoparasite of cervids that harbours haemotrophic Bartonella. A prerequisite for the vector competence of the deer ked is the vertical transmission of the pathogen from the mother to its progeny and transstadial transmission from pupa to winged adult. We screened 1154 pupae and 59 pools of winged adult deer keds from different areas in Finland for Bartonella DNA using PCR. Altogether 13 pupa samples and one winged adult deer ked were positive for the presence of Bartonella DNA. The amplified sequences were closely related to either B. schoenbuchensis or B. bovis. The same lineages were identified in eight blood samples collected from free-ranging moose. This is the first demonstration of Bartonella spp. DNA in a winged adult deer ked and, thus, evidence for potential transstadial transmission of Bartonella spp. in the species

Published
2017

12. Co-Infecting reptarenaviruses can be vertically transmitted in Boa Constrictor

Author

Keller, Saskia, Hetzel, Udo, Sironen, T, Korzyukov, Y, Vapalahti, O, Kipar, Anja, Hepojoki, Jussi, Keller, Saskia, Hetzel, Udo, Sironen, T, Korzyukov, Y, Vapalahti, O, Kipar, Anja, and Hepojoki, Jussi

Abstract

Boid inclusion body disease (BIBD) is an often fatal disease affecting mainly constrictor snakes. BIBD has been associated with infection, and more recently with coinfection, by various reptarenavirus species (family Arenaviridae). Thus far BIBD has only been reported in captive snakes, and neither the incubation period nor the route of transmission are known. Herein we provide strong evidence that co-infecting reptarenavirus species can be vertically transmitted in Boa constrictor. In total we examined five B. constrictor clutches with offspring ranging in age from embryos over perinatal abortions to juveniles. The mother and/or father of each clutch were initially diagnosed with BIBD and/or reptarenavirus infection by detection of the pathognomonic inclusion bodies (IB) and/or reptarenaviral RNA. By applying next-generation sequencing and de novo sequence assembly we determined the "reptarenavirome" of each clutch, yielding several nearly complete L and S segments of multiple reptarenaviruses. We further confirmed vertical transmission of the co-infecting reptarenaviruses by species-specific RT-PCR from samples of parental animals and offspring. Curiously, not all offspring obtained the full parental "reptarenavirome". We extended our findings by an in vitro approach; cell cultures derived from embryonal samples rapidly developed IB and promoted replication of some or all parental viruses. In the tissues of embryos and perinatal abortions, viral antigen was sometimes detected, but IB were consistently seen only in the juvenile snakes from the age of 2 mo onwards. In addition to demonstrating vertical transmission of multiple species, our results also indicate that reptarenavirus infection induces BIBD over time in the offspring.

Published
2017

15. Fur Animal Epidemic Necrotic Pyoderma

Author

Nordgren, H., primary, Aaltonen, K., additional, Sironen, T., additional, Kinnunen, P.M., additional, Kivistö, I., additional, Raunio-Saarnisto, M., additional, Moisander-Jylhä, A.-M., additional, Korpela, J., additional, Kokkonen, U.-M., additional, Hetzel, U., additional, Sukura, A., additional, and Vapalahti, O., additional

Published
2016
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18. Novel flaviviruses from mosquitoes: Mosquito-specific evolutionary lineages within the phylogenetic group of mosquito-borne flaviviruses

Author

Huhtamo, E, Cook, S, Moureau, G, Uzcátegui, NY, Sironen, T, Kuivanen, S, Putkuri, N, Kurkela, S, Harbach, RE, Firth, AE, Vapalahti, O, Gould, EA, de Lamballerie, X, Huhtamo, E, Cook, S, Moureau, G, Uzcátegui, NY, Sironen, T, Kuivanen, S, Putkuri, N, Kurkela, S, Harbach, RE, Firth, AE, Vapalahti, O, Gould, EA, and de Lamballerie, X

Published
2014

19. Reply to 'Updated phylogenetic analysis of arenaviruses detected in boid snakes'

Author

Hetzel, U, Sironen, T, Laurinmäki, P, Liljeroos, L, Patjas, A, Henttonen, H, Vaheri, A, Artelt, A, Kipar, A, Butcher, S J, Vapalahti, O, Hepojoki, J, Hetzel, U, Sironen, T, Laurinmäki, P, Liljeroos, L, Patjas, A, Henttonen, H, Vaheri, A, Artelt, A, Kipar, A, Butcher, S J, Vapalahti, O, and Hepojoki, J

Published
2014

21. Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose blood in Finland

Author

KORHONEN, E. M., primary, PÉREZ VERA, C., additional, PULLIAINEN, A.T., additional, SIRONEN, T., additional, AALTONEN, K., additional, KORTET, R., additional, HÄRKÖNEN, L., additional, HÄRKÖNEN, S., additional, PAAKKONEN, T., additional, NIEMINEN, P., additional, MUSTONEN, A-M., additional, YLÖNEN, H., additional, and VAPALAHTI, O., additional

Published
2014
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25. Recent increase in prevalence of antibodies to Dobrava-Belgrade virus (DOBV) in yellow-necked mice in northern Italy.

Author

Stärk, Katharina D.C., Morgan, Dilys, RIZZOLI, A., TAGLIAPIETRA, V., ROSÀ, R., HAUFFE, H. C., MARINI, G., VOUTILAINEN, L., SIRONEN, T., ROSSI, C., ARNOLDI, D., and HENTTONEN, H.

Abstract

Dobrava-Belgrade virus (DOBV) is the most pathogenic hantavirus in Europe with a case-fatality rate of up to 12%. To detect changes in risk for humans, the prevalence of antibodies to DOBV has been monitored in a population of Apodemus flavicollis in the province of Trento (northern Italy) since 2000, and a sudden increase was observed in 2010. In the 13-year period of this study, 2077 animals were live-trapped and mean hantavirus seroprevalence was 2·7% (s.e. = 0·3%), ranging from 0% (in 2000, 2002 and 2003) to 12·5% (in 2012). Climatic (temperature and precipitation) and host (rodent population density, rodent weight and sex, and larval tick burden) variables were analysed using Generalized Linear Models and multi-model inference to select the best model. Climatic changes (mean annual precipitation and maximum temperature) and individual body mass had a positive effect on hantavirus seroprevalence. Other possible drivers affecting the observed pattern need to be studied further. [ABSTRACT FROM AUTHOR]

Published
2015
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27. Analysis of complete Puumala virus genome, Finland.

Author

Plyusnina A, Razzauti M, Sironen T, Niemimaa J, Vapalahti O, Vaheri A, Henttonen H, Plyusnin A, Plyusnina, Angelina, Razzauti, Maria, Sironen, Tarja, Niemimaa, Jukka, Vapalahti, Olli, Vaheri, Antti, Henttonen, Heikki, and Plyusnin, Alexander

Abstract

Puumala virus causes nephropathia epidemica, a rodent-borne zoonosis that is endemic to Europe. We sequenced the complete Puumala virus genome that was directly recovered from a person who died and compared it with those of viruses from local bank voles. The virus strain involved was neither a unique nor rare genetic variant. [ABSTRACT FROM AUTHOR]

Published
2012
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28. Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

Author

Alm E., Broberg E.K., Connor T., Hodcroft E.B., Komissarov A.B., Maurer-Stroh S., Melidou A., Neher R.A., O'Toole A., Pereyaslov D., Beerenwinkel N., Posada-Cespedes S., Jablonski K.P., Ferreira P.F., Topolsky I., Avsic-Zupanc T., Korva M., Poljak M., Zakotnik S., Zorec T.M., Bragstad K., Hungnes O., Stene-Johansen K., Reusken C., Meijer A., Vennema H., Ruiz-Roldan L., Bracho M.A., Garcia-Gonzalez N., Chiner-Oms A., Cancino-Munoz I., Comas I., Goig G.A., Torres-Puente M., Lopez M.G., Martinez-Priego L., D'Auria G., Ruiz-Hueso P., Ferrus-Abad L., de Marco G., Galan-Vendrell I., Carbo-Ramirez S., Ruiz-Rodriguez P., Coscolla M., Polackova K., Kramna L., Cinek O., Richter J., Krashias G., Tryfonos C., Bashiardes S., Koptides D., Christodoulou C., Bartolini B., Gruber C.E., Di Caro A., Castilletti C., Stefani F., Rimoldi S.G., Romeri F., Salerno F., Polesello S., Nagy A., Jirincova H., Vecerova J., Novakova L., Cordey S., Murtskhvaladze M., Kotaria N., Schar T., Beisel C., Vugrek O., Rokic F., Trgovec-Greif L., Jurak I., Rukavina T., Sucic N., Schonning K., Karst S.M., Kirkegaard R.H., Michaelsen T.Y., Sorensen E.A., Knutson S., Brandt J., Le-Quy V., Sorensen T., Petersen C., Pedersen M.S., Larsen S.L., Skov M.N., Rasmussen M., Fonager J., Fomsgaard A., Maksyutov R.A., Gavrilova E.V., Pyankov O.V., Bodnev S.A., Tregubchak T.V., Shvalov A.N., Antonets D.V., Resende P.C., Goya S., Perrin A., Lee R.T., Yadahalli S., Han A.X., Russell C.A., Schmutz S., Zaheri M., Kufner V., Huber M., Trkola A., Antwerpen M., Walter M.C., van der Werf S., Gambaro F., Behillil S., Enouf V., Donati F., Ustinova M., Rovite V., Klovins J., Savicka O., Wienecke-Baldacchino A.K., Ragimbeau C., Fournier G., Mossong J., Aberle S.W., Haukland M., Enkirch T., Advani A., Karlberg M.L., Lindsjo O.K., Broddesson S., Slavikova M., Lickova M., Klempa B., Staronova E., Ticha E., Szemes T., Rusnakova D., Stadler T., Quer J., Anton A., Andres C., Pinana M., Garcia-Cehic D., Pumarola T., Izopet J., Gioula G., Exindari M., Papa A., Chatzidimitriou D., Metallidis S., Pappa S., Macek M., Geryk J., Broz P., Briksi A., Hubacek P., Drevinek P., Zajac M., Kvapil P., Holub M., Kvapilova K., Novotny A., Kasny M., Klempt P., Vapalahti O., Smura T., Sironen T., Selhorst P., Anthony C., Arien K., Simon-Loriere E., Rabalski L., Bienkowska-Szewczyk K., Borges V., Isidro J., Gomes J.P., Guiomar R., Pechirra P., Costa I., Duarte S., Vieira L., Pyrc K., Zuckerman N.S., Turdikulova S., Abdullaev A., Dalimova D., Abdurakhimov A., Tagliabracci A., Alessandrini F., Melchionda F., Onofri V., Turchi C., Bagnarelli P., Menzo S., Caucci S., Di Sante L., Popa A., Genger J.-W., Agerer B., Lercher A., Endler L., Smyth M., Penz T., Schuster M., Senekowitsch M., Laine J., Bock C., Bergthaler A., Shevtsov A., Kalendar R., Ramanculov Y., Graf A., Muenchhoff M., Keppler O.T., Krebs S., Blum H., Marcello A., Licastro D., D'Agaro P., Laubscher F., Vidanovic D., Tesovic B., Volkening J., Clementi N., Mancini N., Rupnik M., Mahnic A., Walker A., Houwaart T., Wienemann T., Vasconcelos M.K., Strelow D., Jensen B.-E.O., Senff T., Hulse L., Adams O., Andree M., Hauka S., Feldt T., Keitel V., Kindgen-Milles D., Timm J., Pfeffer K., Dilthey A.T., Moore C., Ozdarendeli A., Pavel S.T.I., Yetiskin H., Aydin G., Holyavkin C., Uygut M.A., Cevik C., Shchetinin A., Gushchin V., Dinler-Doganay G., Doganay L., Kizilboga-Akgun T., Karacan I., Pancer K., Maes P., Marti-Carreras J., Wawina-Bokalanga T., Vanmechelen B., Thurmer A., Wedde M., Durrwald R., von Kleist M., Drechsel O., Wolff T., Fuchs S., Kmiecinski R., Michel J., Nitsche A., Casas I., Caballero M.I., Zaballos A., Jimenez P., Jimenez M., Fernandez S.M., Fernandez S.V., de la Plaza I.C., Fadeev A., Ivanova A., Sergeeva M., Stefanelli P., Estee Torok M., Hall G., da Silva Filipe A., Turtle L., Afifi S., McCluggage K., Beer R., Ledesma J., Maksimovic J., Spellman K., Hamilton W.L., Marchbank A., Southgate J.A., Underwood A., Taylor B., Yeats C., Abudahab K., Gemmell M.R., Eccles R., Lucaci A., Nelson C.A., Rainbow L., Whitehead M., Gregory R., Haldenby S., Paterson S., Hughes M.A., Curran M.D., Baker D., Tucker R., Green L.R., Feltwell T., Halstead F.D., Wyles M., Jahun A.S., Ahmad S.S.Y., Georgana I., Goodfellow I., Yakovleva A., Meredith L.W., Gavriil A., Awan A.R., Fisher C., Edgeworth J., Lynch J., Moore N., Williams R., Kidd S.P., Cortes N., Brunker K., McCrone J.T., Quick J., Duckworth N., Walsh S., Sloan T., Ludden C., George R.P., Eltringham G., Brown J.R., Aranday-Cortes E., Shepherd J.G., Hughes J., Li K.K., Williams T.C., Johnson N., Jesudason N., Mair D., Thomson E., Shah R., Parr Y.A., Carmichael S., Robertson D.L., Nomikou K., Broos A., Niebel M., Smollett K., Tong L., Miah S., Wittner A., Phillips N., Payne B., Dewar R., Holmes A., Bolt F., Price J.R., Mookerjee S., Sethi D.K., Potter W., Stanley R., Prakash R., Dervisevic S., Graham J.C., Nelson A., Smith D., Young G.R., Yew W.C., Todd J.A., Trebes A., Andersson M., Bull M., Watkins J., Birchley A., Gatica-Wilcox B., Gilbert L., Kumziene-Summerhayes S., Rey S., Chauhan A., Butcher E., Bicknell K., Elliott S., Glaysher S., Lackenby A., Bibby D., Platt S., Mohamed H., Machin N.W., Mbisa J.L., Evans J., Perry M., Pacchiarini N., Corden S., Adams A.G., Gaskin A., Coombs J., Graham L.J., Cottrell S., Morgan M., Gifford L., Kolyva A., Rudder S.J., Trotter A.J., Mather A.E., Aydin A., Page A.J., Kay G.L., de Oliveira Martins L., Yasir M., Alikhan N.-F., Thomson N.M., Gilroy R., Kingsley R.A., O'Grady J., Gutierrez A.V., Diaz M., Viet T.L., Tedim A.P., Adriaenssens E.M., Patrick Mcclure C., Sang F., Clark G., Howson-Wells H.C., Debebe J., Ball J., Chappell J., Khakh M., Carlile M., Loose M., Lister M.M., Holmes N., Tsoleridis T., Fleming V.M., Wright V., Smith W., Gallagher M.D., Parker M., Partridge D.G., Evans C., Baker P., Essex S., Liggett S., Keeley A.J., Bashton M., Rooke S., Dervisavic S., Meader E.J., Lopez C.E.B., Angyal A., Kristiansen M., Tutill H.J., Findlay J., Mestek-Boukhibar L., Forrest L., Dyal P., Williams R.J., Panchbhaya Y., Williams C.A., Roy S., Pandey S., Stockton J., Loman N.J., Poplawski R., Nicholls S., Rowe W.P.M., Khokhar F., Pinckert M.L., Hosmillo M., Chaudhry Y., Caller L.G., Davidson R.K., Griffith L., Rambaut A., Jackson B., Colquhoun R., Hill V., Nichols J., Asamaphan P., Darby A., Jackson K.A., Iturriza-Gomara M., Vamos E.E., Green A., Aanensen D., Bonsall D., Buck D., Macintyre-Cockett G., de Cesare M., Pybus O., Golubchik T., Scarlett G., Loveson K.F., Robson S.C., Beckett A., Lindsey B., Groves D.C., Parsons P.J., McHugh M.P., Barnes J.D., Manso C.F., Grammatopoulos D., Menger K.E., Harrison E., Gunson R., Peacock S.J., Gonzalez G., Carr M., Mihaela L., Popovici O., Brytting M., Bresner C., Fuller W., Workman T., Mentis A.F., Kossyvakis A., Karamitros T., Pogka V., Kalliaropoulos A., Horefti E., Kontou A., Martinez-Gonzalez B., Labropoulou V., Voulgari-Kokota A., Evangelidou M., Bizta P., Belimezi M., Lambrechts L., Doymaz M.Z., Yazici M.K., Cetin N.S., Karaaslan E., Kallio-Kokko H., Virtanen J., Suvanto M., Nguyen P.T., Ellonen P., Hannula S., Kangas H., Sreenu V.B., Burian K., Terhes G., Gombos K., Gyenesei A., Urban P., Herczeg R., Jakab F., Kemenesi G., Toth G.E., Somogyi B., Zana B., Zeghbib S., Kuczmog A., Foldes F., Lanszki Z., Madai M., Papp H., Pereszlenyi C.I., Babinszky G.C., Dudas G., Csoma E., Abou Tayoun A.N., Alsheikh-Ali A.A., Loney T., Nowotny N., Abdul-Wahab O., Gonzalez-Candelas F., Andersen M.H., Taylor S., MARTI CARRERAS, Joan, Vanmechelen, Bert, Wawina, Tony, Medical Microbiology and Infection Prevention, AII - Infectious diseases, WHO European Region Sequencing Lab, GISAID EpiCoV Grp, Erik, Alm, Eeva K, Broberg, Thomas, Connor, Emma B, Hodcroft, Andrey B, Komissarov, Sebastian, Maurer-Stroh, Angeliki, Melidou, Richard A, Neher, Áine, O’Toole, Dmitriy, Pereyaslov, WHO European Region sequencing laboratories and GISAID EpiCoV group (Niko Beerenwinkel, The, Posada-Céspedes, Susana, Philipp, Kim, Jablonski, Falé Ferreira, Pedro, Topolsky, Ivan, Avšičžupanc, Tatjana, Korva, Miša, Poljak, Mario, Zakotnik, Samo, Tomaž, Zorec, Mark, Bragstad, Karoline, Hungnes, Olav, Stene-Johansen, Kathrine, Reusken, Chantal, Meijer, Adam, Vennema, Harry, Ruiz-Roldán, Lidia, Alma Bracho, María, García-González, Neri, Chiner-Oms, Álvaro, Cancino-Muñoz, Irving, Comas, Iñaki, A Goig, Galo, Torres-Puente, Manuela, G López, Mariana, Martínez-Priego, Llúcia, D’Auria, Giuseppe, LoretoFerrús-Abad, de Marco, Griselda, Galan-Vendrell, Inmaculada, Carbó-Ramirez, Sandra, Ruíz-Hueso, Paula, Coscollá, Mireia, Polackova, Katerina, Kramna, Lenka, Cinek, Ondrej, Richter, Jan, Krashias, George, Tryfonos, Christina, Bashiardes, Stavro, Koptides, Dana, Christodoulou, Christina, Bartolini, Barbara, Em Gruber, Cesare, Di Caro, Antonino, Castilletti, Concetta, Stefani, Fabrizio, Giordana Rimoldi, Sara, Romeri, Francesca, Salerno, Franco, Polesello, Stefano, Nagy, Alexander, Jirincova, Helena, Vecerova, Jaromira, Novakova, Ludmila, Cordey, Samuel, Murtskhvaladze, Marine, Kotaria, Nato, Schär, Tobia, Beisel, Christian, Vugrek, Oliver, Rokić, Filip, Trgovecgreif, Lovro, Jurak, Igor, Rukavina, Tomislav, Sučić, Neven, Schønning, Kristian, M Karst, Søren, H Kirkegaard, Rasmu, Y Michaelsen, Thoma, Aa Sørensen, Emil, Knutson, Simon, Brandt, Jakob, Le-Quy, Vang, Sørensen, Trine, Petersen, Celine, Schou Pedersen, Martin, Løkkegaard Larsen, Sanne, Nielsine Skov, Marianne, Rasmussen, Morten, Fonager, Jannik, Fomsgaard, Ander, Amirovich Maksyutov, Rinat, Vasil’Evna Gavrilova, Elena, Victorovich Pyankov, Oleg, Alexandrovich Bodnev, Sergey, Vladimirovna Tregubchak, Tatyana, Nikolayevich Shvalov, Alexander, Victorovich Antonets, Deni, Cristina Resende, Paola, Goya, Stephanie, Perrin, Amandine, Tc Lee, Raphael, Yadahalli, Shilpa, X Han, Alvin, A Russell, Colin, Schmutz, Stefan, Zaheri, Maryam, Kufner, Verena, Huber, Michael, Trkola, Alexandra, Antwerpen, Marku, C Walter, Mathia, van der Werf, Sylvie, Gambaro, Fabiana, Behillil, Sylvie, Enouf, Vincent, Donati, Flora, Ustinova, Monta, Rovite, Vita, Klovins, Jani, Savicka, Oksana, K Wienecke-Baldacchino, Anke, Ragimbeau, Catherine, Fournier, Guillaume, Mossong, Joël, W Aberle, Stephan, Haukland, Mattia, Enkirch, Theresa, Advani, Abdolreza, Lind Karlberg, Maria, Karlsson Lindsjö, Oskar, Broddesson, Sandra, Sláviková, Monika, Ličková, Martina, Klempa, Bori, Staroňová, Edita, Tichá, Elena, Szemes, Tomáš, Rusňáková, Diana, Stadler, Tanja, Quer, Josep, Anton, Andre, Andres, Cristina, Piñana, Maria, Garcia-Cehic, Damir, Pumarola, Toma, Izopet, Jacque, Gioula, Georgia, Exindari, Maria, Papa, Anna, Chatzidimitriou, Dimitrio, Metallidis, Symeon, Pappa, Stella, Macek Jr, Milan, Geryk, Jan, Brož, Petr, Briksí, Aleš, Hubáček, Petr, Dřevínek, Pavel, Zajac, Miroslav, Kvapil, Petr, Holub, Michal, Kvapilová, Kateřina, Novotný, Adam, Kašný, Martin, Klempt, Petr, Vapalahti, Olli, Smura, Teemu, Sironen, Tarja, Selhorst, Philippe, Anthony, Colin, Ariën, Kevin, Simon-Loriere, Etienne, Rabalski, Lukasz, Bienkowska-Szewczyk, Krystyna, Borges, Vítor, Isidro, Joana, Paulo Gomes, João, Guiomar, Raquel, Pechirra, Pedro, Costa, Inê, Duarte, Sílvia, Vieira, Luí, Pyrc, Krzysztof, S Zuckerman, Neta, Turdikulova, Shahlo, Abdullaev, Alisher, Dalimova, Dilbar, Abdurakhimov, Abror, Tagliabracci, Adriano, Alessandrini, Federica, Melchionda, Filomena, Onofri, Valerio, Turchi, Chiara, Bagnarelli, Patrizia, Menzo, Stefano, Caucci, Sara, Di Sante, Laura, Popa, Alexandra, Genger, Jakob-Wendelin, Agerer, Benedikt, Lercher, Alexander, Endler, Luka, Smyth, Mark, Penz, Thoma, Schuster, Michael, Senekowitsch, Martin, Laine, Jan, Bock, Christoph, Bergthaler, Andrea, Shevtsov, Alexandr, Kalendar, Ruslan, Ramanculov, Yerlan, Graf, Alexander, Muenchhoff, Maximilian, T Keppler, Oliver, Krebs, Stefan, Blum, Helmut, Marcello, Alessandro, Licastro, Danilo, D’Agaro, Pierlanfranco, Laubscher, Florian, Vidanovic, Dejan, Tesovic, Bojana, Volkening, Jeremy, Clementi, Nicola, Mancini, Nicasio, Rupnik, Maja, Mahnic, Aleksander, Walker, Andrea, Houwaart, Torsten, Wienemann, Tobia, Kohns Vasconcelos, Malte, Strelow, Daniel, Ole Jensen, Björn-Erik, Senff, Tina, Hülse, Lisanna, Adams, Ortwin, Andree, Marcel, Hauka, Sandra, Feldt, Torsten, Keitel, Verena, Kindgen-Milles, Detlef, Timm, Jörg, Pfeffer, Klau, T Dilthey, Alexander, Moore, Catherine, Ozdarendeli, Aykut, Terkis Islam Pavel, Shaikh, Yetiskin, Hazel, Aydin, Gunsu, Holyavkin, Can, Ali Uygut, Muhammet, Cevik, Ceren, Shchetinin, Alexey, Gushchin, Vladimir, Dinler-Doganay, Gizem, Doganay, Levent, Kizilboga-Akgun, Tugba, Karacan, Ilker, Pancer, Katarzyna, Maes, Piet, Martí-Carreras, Joan, Wawina-Bokalanga, Tony, Thürmer, Andrea, Wedde, Marianne, Dürrwald, Ralf, Von Kleist, Max, Drechsel, Oliver, Wolff, Thorsten, Fuchs, Stephan, Kmiecinski, Rene, Michel, Janine, Nitsche, Andrea, Casas, Inmaculada, Iglesias Caballero, María, Zaballos, Ángel, Jiménez, Pilar, Jiménez, Mercede, Monzón Fernández, Sara, Varona Fernández, Sarai, Cuesta De La Plaza, Isabel, Fadeev, Artem, Ivanova, Anna, Sergeeva, Mariia, Stefanelli, Paola, Estee Torok, M, Hall, Grant, da Silva Filipe, Ana, Turtle, Lance, Afifi, Safiah, Mccluggage, Kathryn, Beer, Robert, Ledesma, Juan, Maksimovic, Joshua, Spellman, Karla, L Hamilton, William, Marchbank, Angela, Alexander Southgate, Joel, Underwood, Anthony, Taylor, Ben, Yeats, Corin, Abudahab, Khalil, R Gemmell, Matthew, Eccles, Richard, Lucaci, Anita, Abigail Nelson, Charlotte, Rainbow, Lucille, Whitehead, Mark, Gregory, Richard, Haldenby, Sam, Paterson, Steve, A Hughes, Margaret, D Curran, Martin, Baker, David, Tucker, Rachel, R Green, Luke, Feltwell, Theresa, D Halstead, Fenella, Wyles, Matthew, S Jahun, Aminu, Y Ahmad, Shazaad S, Georgana, Iliana, Goodfellow, Ian, Yakovleva, Anna, W Meredith, Luke, Gavriil, Artemi, Raza Awan, Ali, Fisher, Chloe, Jonathan, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Cardiff University, Public Health Wales [Cardiff, Royaume uni], University of Basel (Unibas), Research Institute of Influenza, St. Petersburg, Russia, Agency for science, technology and research [Singapore] (A*STAR), National University of Singapore (NUS), University of Edinburgh, WHO Regional Office for Europe [Copenhagen], We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible, The WHO European Region sequencing laboratories and GISAID EpiCoV group*: Niko Beerenwinkel, Susana Posada-Céspedes, Kim Philipp Jablonski, Pedro Falé Ferreira, Ivan Topolsky, Tatjana Avšič-Županc, Miša Korva, Mario Poljak, Samo Zakotnik, Tomaž Mark Zorec, Karoline Bragstad, Olav Hungnes, Kathrine Stene-Johansen, Chantal Reusken, Adam Meijer, Harry Vennema, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Álvaro Chiner-Oms, Irving Cancino-Muñoz, Iñaki Comas, Galo A Goig, Manuela Torres-Puente, Mariana G López, Llúcia Martínez-Priego, Giuseppe D'Auria, Paula Ruíz-Hueso, Loreto Ferrús-Abad, Griselda de Marco, Inmaculada Galan-Vendrell, Sandra Carbó-Ramirez, Paula Ruiz-Rodriguez, Mireia Coscollá, Katerina Polackova, Lenka Kramna, Ondrej Cinek, Jan Richter, George Krashias, Christina Tryfonos, Stavros Bashiardes, Dana Koptides, Christina Christodoulou, Barbara Bartolini, Cesare Em Gruber, Antonino Di Caro, Concetta Castilletti, Fabrizio Stefani, Sara Giordana Rimoldi, Francesca Romeri, Franco Salerno, Stefano Polesello, Alexander Nagy, Helena Jirincova, Jaromira Vecerova, Ludmila Novakova, Samuel Cordey, Marine Murtskhvaladze, Nato Kotaria, Tobias Schär, Christian Beisel, Oliver Vugrek, Filip Rokić, Lovro Trgovec-Greif, Igor Jurak, Tomislav Rukavina, Neven Sučić, Kristian Schønning, Søren M Karst, Rasmus H Kirkegaard, Thomas Y Michaelsen, Emil Aa Sørensen, Simon Knutson, Jakob Brandt, Vang Le-Quy, Trine Sørensen, Celine Petersen, Martin Schou Pedersen, Sanne Løkkegaard Larsen, Marianne Nielsine Skov, Morten Rasmussen, Jannik Fonager, Anders Fomsgaard, Rinat Amirovich Maksyutov, Elena Vasil'Evna Gavrilova, Oleg Victorovich Pyankov, Sergey Alexandrovich Bodnev, Tatyana Vladimirovna Tregubchak, Alexander Nikolayevich Shvalov, Denis Victorovich Antonets, Paola Cristina Resende, Stephanie Goya, Amandine Perrin, Raphael Tc Lee, Shilpa Yadahalli, Alvin X Han, Colin A Russell, Stefan Schmutz, Maryam Zaheri, Verena Kufner, Michael Huber, Alexandra Trkola, Markus Antwerpen, Mathias C Walter, Sylvie van der Werf, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Flora Donati, Monta Ustinova, Vita Rovite, Janis Klovins, Oksana Savicka, Anke K Wienecke-Baldacchino, Catherine Ragimbeau, Guillaume Fournier, Joël Mossong, Stephan W Aberle, Mattias Haukland, Theresa Enkirch, Abdolreza Advani, Maria Lind Karlberg, Oskar Karlsson Lindsjö, Sandra Broddesson, Monika Sláviková, Martina Ličková, Boris Klempa, Edita Staroňová, Elena Tichá, Tomáš Szemes, Diana Rusňáková, Tanja Stadler, Josep Quer, Andres Anton, Cristina Andres, Maria Piñana, Damir Garcia-Cehic, Tomas Pumarola, Jacques Izopet, Georgia Gioula, Maria Exindari, Anna Papa, Dimitrios Chatzidimitriou, Symeon Metallidis, Stella Pappa, Milan Macek Jr, Jan Geryk, Petr Brož, Aleš Briksí, Petr Hubáček, Pavel Dřevínek, Miroslav Zajac, Petr Kvapil, Michal Holub, Kateřina Kvapilová, Adam Novotný, Martin Kašný, Petr Klempt, Olli Vapalahti, Teemu Smura, Tarja Sironen, Philippe Selhorst, Colin Anthony, Kevin Ariën, Etienne Simon-Loriere, Lukasz Rabalski, Krystyna Bienkowska-Szewczyk, Vítor Borges, Joana Isidro, João Paulo Gomes, Raquel Guiomar, Pedro Pechirra, Inês Costa, Sílvia Duarte, Luís Vieira, Krzysztof Pyrc, Neta S Zuckerman, Shahlo Turdikulova, Alisher Abdullaev, Dilbar Dalimova, Abror Abdurakhimov, Adriano Tagliabracci, Federica Alessandrini, Filomena Melchionda, Valerio Onofri, Chiara Turchi, Patrizia Bagnarelli, Stefano Menzo, Sara Caucci, Laura Di Sante, Alexandra Popa, Jakob-Wendelin Genger, Benedikt Agerer, Alexander Lercher, Lukas Endler, Mark Smyth, Thomas Penz, Michael Schuster, Martin Senekowitsch, Jan Laine, Christoph Bock, Andreas Bergthaler, Alexandr Shevtsov, Ruslan Kalendar, Yerlan Ramanculov, Alexander Graf, Maximilian Muenchhoff, Oliver T Keppler, Stefan Krebs, Helmut Blum, Alessandro Marcello, Danilo Licastro, Pierlanfranco D'Agaro, Florian Laubscher, Dejan Vidanovic, Bojana Tesovic, Jeremy Volkening, Nicola Clementi, Nicasio Mancini, Maja Rupnik, Aleksander Mahnic, Andreas Walker, Torsten Houwaart, Tobias Wienemann, Malte Kohns Vasconcelos, Daniel Strelow, Björn-Erik Ole Jensen, Tina Senff, Lisanna Hülse, Ortwin Adams, Marcel Andree, Sandra Hauka, Torsten Feldt, Verena Keitel, Detlef Kindgen-Milles, Jörg Timm, Klaus Pfeffer, Alexander T Dilthey, Catherine Moore, Aykut Ozdarendeli, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Gunsu Aydin, Can Holyavkin, Muhammet Ali Uygut, Ceren Cevik, Alexey Shchetinin, Vladimir Gushchin, Gizem Dinler-Doganay, Levent Doganay, Tugba Kizilboga-Akgun, Ilker Karacan, Katarzyna Pancer, Piet Maes, Joan Martí-Carreras, Tony Wawina-Bokalanga, Bert Vanmechelen, Andrea Thürmer, Marianne Wedde, Ralf Dürrwald, Max Von Kleist, Oliver Drechsel, Thorsten Wolff, Stephan Fuchs, Rene Kmiecinski, Janine Michel, Andreas Nitsche, Inmaculada Casas, María Iglesias Caballero, Ángel Zaballos, Pilar Jiménez, Mercedes Jiménez, Sara Monzón Fernández, Sarai Varona Fernández, Isabel Cuesta De La Plaza, Artem Fadeev, Anna Ivanova, Mariia Sergeeva, Paola Stefanelli, M Estee Torok, Grant Hall, Ana da Silva Filipe, Lance Turtle, Safiah Afifi, Kathryn Mccluggage, Robert Beer, Juan Ledesma, Joshua Maksimovic, Karla Spellman, William L Hamilton, Angela Marchbank, Joel Alexander Southgate, Anthony Underwood, Ben Taylor, Corin Yeats, Khalil Abudahab, Matthew R Gemmell, Richard Eccles, Anita Lucaci, Charlotte Abigail Nelson, Lucille Rainbow, Mark Whitehead, Richard Gregory, Sam Haldenby, Steve Paterson, Margaret A Hughes, Martin D Curran, David Baker, Rachel Tucker, Luke R Green, Theresa Feltwell, Fenella D Halstead, Matthew Wyles, Aminu S Jahun, Shazaad S Y Ahmad, Iliana Georgana, Ian Goodfellow, Anna Yakovleva, Luke W Meredith, Artemis Gavriil, Ali Raza Awan, Chloe Fisher, Jonathan Edgeworth, Jessica Lynch, Nathan Moore, Rebecca Williams, Stephen P Kidd, Nicholas Cortes, Kirstyn Brunker, John T Mccrone, Joshua Quick, Nichola Duckworth, Sarah Walsh, Tim Sloan, Catherine Ludden, Ryan P George, Gary Eltringham, Julianne R Brown, Elihu Aranday-Cortes, James G Shepherd, Joseph Hughes, Kathy K Li, Thomas C Williams, Natasha Johnson, Natasha Jesudason, Daniel Mair, Emma Thomson, Rajiv Shah, Yasmin A Parr, Stephen Carmichael, David L Robertson, Kyriaki Nomikou, Alice Broos, Marc Niebel, Katherine Smollett, Lily Tong, Shahjahan Miah, Anita Wittner, Nicole Phillips, Brendan Payne, Rebecca Dewar, Alison Holmes, Frances Bolt, James R Price, Siddharth Mookerjee, Dheeraj K Sethi, Will Potter, Rachael Stanley, Reenesh Prakash, Samir Dervisevic, Jonathan Clive Graham, Andrew Nelson, Darren Smith, Gregory R Young, Wen Chyin Yew, John A Todd, Amy Trebes, Monique Andersson, Matthew Bull, Joanne Watkins, Alec Birchley, Bree Gatica-Wilcox, Lauren Gilbert, Sara Kumžiene-Summerhayes, Sara Rey, Anoop Chauhan, Ethan Butcher, Kelly Bicknell, Scott Elliott, Sharon Glaysher, Angie Lackenby, David Bibby, Steven Platt, Hodan Mohamed, Nicholas William Machin, Jean Lutamyo Mbisa, Jonathan Evans, Malorie Perry, Nicole Pacchiarini, Sally Corden, Alexander Geraint Adams, Amy Gaskin, Jason Coombs, Lee John Graham, Simon Cottrell, Mari Morgan, Laura Gifford, Anastasia Kolyva, Steven John Rudder, Alexander J Trotter, Alison E Mather, Alp Aydin, Andrew J Page, Gemma L Kay, Leonardo de Oliveira Martins, Muhammad Yasir, Nabil-Fareed Alikhan, Nicholas M Thomson, Rachel Gilroy, Robert A Kingsley, Justin O'Grady, Ana Victoria Gutierrez, Maria Diaz, Thanh Le Viet, Ana P Tedim, Evelien M Adriaenssens, C Patrick Mcclure, Christopher Moore, Fei Sang, Gemma Clark, Hannah C Howson-Wells, Johnny Debebe, Jonathan Ball, Joseph Chappell, Manjinder Khakh, Matthew Carlile, Matthew Loose, Michelle M Lister, Nadine Holmes, Theocharis Tsoleridis, Vicki M Fleming, Victoria Wright, Wendy Smith, Michael D Gallagher, Matthew Parker, David G Partridge, Cariad Evans, Paul Baker, Sarah Essex, Steven Liggett, Alexander J Keeley, Matthew Bashton, Stefan Rooke, Samir Dervisevic, Emma Jane Meader, Carlos Enrique Balcazar Lopez, Adrienn Angyal, Mark Kristiansen, Helena J Tutill, Jacqueline Findlay, Lamia Mestek-Boukhibar, Leysa Forrest, Patricia Dyal, Rachel J Williams, Yasmin Panchbhaya, Charlotte A Williams, Sunando Roy, Sarojini Pandey, Jo Stockton, Nicholas J Loman, Radoslaw Poplawski, Samuel Nicholls, W P M Rowe, Fahad Khokhar, Malte Lars Pinckert, Myra Hosmillo, Yasmin Chaudhry, Laura G Caller, Rose K Davidson, Luke Griffith, Andrew Rambaut, Ben Jackson, Rachel Colquhoun, Verity Hill, Jenna Nichols, Patawee Asamaphan, Alistair Darby, Kathryn A Jackson, Miren Iturriza-Gomara, Ecaterina Edith Vamos, Angie Green, David Aanensen, David Bonsall, David Buck, George Macintyre-Cockett, Mariateresa de Cesare, Oliver Pybus, Tanya Golubchik, Garry Scarlett, Katie F Loveson, Samuel C Robson, Angela Beckett, Benjamin 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K., Connor, T., Hodcroft, E. B., Komissarov, A. B., Maurer-Stroh, S., Melidou, A., Neher, R. A., O'Toole, A., Pereyaslov, D., Beerenwinkel, N., Posada-Cespedes, S., Jablonski, K. P., Ferreira, P. F., Topolsky, I., Avsic-Zupanc, T., Korva, M., Poljak, M., Zakotnik, S., Zorec, T. M., Bragstad, K., Hungnes, O., Stene-Johansen, K., Reusken, C., Meijer, A., Vennema, H., Ruiz-Roldan, L., Bracho, M. A., Garcia-Gonzalez, N., Chiner-Oms, A., Cancino-Munoz, I., Comas, I., Goig, G. A., Torres-Puente, M., Lopez, M. G., Martinez-Priego, L., D'Auria, G., Ruiz-Hueso, P., Ferrus-Abad, L., de Marco, G., Galan-Vendrell, I., Carbo-Ramirez, S., Ruiz-Rodriguez, P., Coscolla, M., Polackova, K., Kramna, L., Cinek, O., Richter, J., Krashias, G., Tryfonos, C., Bashiardes, S., Koptides, D., Christodoulou, C., Bartolini, B., Gruber, C. E., Di Caro, A., Castilletti, C., Stefani, F., Rimoldi, S. 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W., Haukland, M., Enkirch, T., Advani, A., Karlberg, M. L., Lindsjo, O. K., Broddesson, S., Slavikova, M., Lickova, M., Klempa, B., Staronova, E., Ticha, E., Szemes, T., Rusnakova, D., Stadler, T., Quer, J., Anton, A., Andres, C., Pinana, M., Garcia-Cehic, D., Pumarola, T., Izopet, J., Gioula, G., Exindari, M., Papa, A., Chatzidimitriou, D., Metallidis, S., Pappa, S., Macek, M., Geryk, J., Broz, P., Briksi, A., Hubacek, P., Drevinek, P., Zajac, M., Kvapil, P., Holub, M., Kvapilova, K., Novotny, A., Kasny, M., Klempt, P., Vapalahti, O., Smura, T., Sironen, T., Selhorst, P., Anthony, C., Arien, K., Simon-Loriere, E., Rabalski, L., Bienkowska-Szewczyk, K., Borges, V., Isidro, J., Gomes, J. P., Guiomar, R., Pechirra, P., Costa, I., Duarte, S., Vieira, L., Pyrc, K., Zuckerman, N. S., Turdikulova, S., Abdullaev, A., Dalimova, D., Abdurakhimov, A., Tagliabracci, A., Alessandrini, F., Melchionda, F., Onofri, V., Turchi, C., Bagnarelli, P., Menzo, S., Caucci, S., Di Sante, L., Popa, A., Genger, J. -W., Agerer, B., Lercher, A., Endler, L., Smyth, M., Penz, T., Schuster, M., Senekowitsch, M., Laine, J., Bock, C., Bergthaler, A., Shevtsov, A., Kalendar, R., Ramanculov, Y., Graf, A., Muenchhoff, M., Keppler, O. T., Krebs, S., Blum, H., Marcello, A., Licastro, D., D'Agaro, P., Laubscher, F., Vidanovic, D., Tesovic, B., Volkening, J., Clementi, N., Mancini, N., Rupnik, M., Mahnic, A., Walker, A., Houwaart, T., Wienemann, T., Vasconcelos, M. K., Strelow, D., Jensen, B. -E. O., Senff, T., Hulse, L., Adams, O., Andree, M., Hauka, S., Feldt, T., Keitel, V., Kindgen-Milles, D., Timm, J., Pfeffer, K., Dilthey, A. T., Moore, C., Ozdarendeli, A., Pavel, S. T. I., Yetiskin, H., Aydin, G., Holyavkin, C., Uygut, M. A., Cevik, C., Shchetinin, A., Gushchin, V., Dinler-Doganay, G., Doganay, L., Kizilboga-Akgun, T., Karacan, I., Pancer, K., Maes, P., Marti-Carreras, J., Wawina-Bokalanga, T., Vanmechelen, B., Thurmer, A., Wedde, M., Durrwald, R., von Kleist, M., Drechsel, O., Wolff, T., Fuchs, S., Kmiecinski, R., Michel, J., Nitsche, A., Casas, I., Caballero, M. I., Zaballos, A., Jimenez, P., Jimenez, M., Fernandez, S. M., Fernandez, S. V., de la Plaza, I. C., Fadeev, A., Ivanova, A., Sergeeva, M., Stefanelli, P., Estee Torok, M., Hall, G., da Silva Filipe, A., Turtle, L., Afifi, S., Mccluggage, K., Beer, R., Ledesma, J., Maksimovic, J., Spellman, K., Hamilton, W. L., Marchbank, A., Southgate, J. A., Underwood, A., Taylor, B., Yeats, C., Abudahab, K., Gemmell, M. R., Eccles, R., Lucaci, A., Nelson, C. A., Rainbow, L., Whitehead, M., Gregory, R., Haldenby, S., Paterson, S., Hughes, M. A., Curran, M. D., Baker, D., Tucker, R., Green, L. R., Feltwell, T., Halstead, F. D., Wyles, M., Jahun, A. S., Ahmad, S. S. Y., Georgana, I., Goodfellow, I., Yakovleva, A., Meredith, L. W., Gavriil, A., Awan, A. R., Fisher, C., Edgeworth, J., Lynch, J., Moore, N., Williams, R., Kidd, S. P., Cortes, N., Brunker, K., Mccrone, J. T., Quick, J., Duckworth, N., Walsh, S., Sloan, T., Ludden, C., George, R. P., Eltringham, G., Brown, J. R., Aranday-Cortes, E., Shepherd, J. G., Hughes, J., Li, K. K., Williams, T. C., Johnson, N., Jesudason, N., Mair, D., Thomson, E., Shah, R., Parr, Y. A., Carmichael, S., Robertson, D. L., Nomikou, K., Broos, A., Niebel, M., Smollett, K., Tong, L., Miah, S., Wittner, A., Phillips, N., Payne, B., Dewar, R., Holmes, A., Bolt, F., Price, J. R., Mookerjee, S., Sethi, D. K., Potter, W., Stanley, R., Prakash, R., Dervisevic, S., Graham, J. C., Nelson, A., Smith, D., Young, G. R., Yew, W. C., Todd, J. A., Trebes, A., Andersson, M., Bull, M., Watkins, J., Birchley, A., Gatica-Wilcox, B., Gilbert, L., Kumziene-Summerhayes, S., Rey, S., Chauhan, A., Butcher, E., Bicknell, K., Elliott, S., Glaysher, S., Lackenby, A., Bibby, D., Platt, S., Mohamed, H., Machin, N. W., Mbisa, J. L., Evans, J., Perry, M., Pacchiarini, N., Corden, S., Adams, A. G., Gaskin, A., Coombs, J., Graham, L. J., Cottrell, S., Morgan, M., Gifford, L., Kolyva, A., Rudder, S. J., Trotter, A. J., Mather, A. E., Aydin, A., Page, A. J., Kay, G. L., de Oliveira Martins, L., Yasir, M., Alikhan, N. -F., Thomson, N. M., Gilroy, R., Kingsley, R. A., O'Grady, J., Gutierrez, A. V., Diaz, M., Viet, T. L., Tedim, A. P., Adriaenssens, E. M., Patrick Mcclure, C., Sang, F., Clark, G., Howson-Wells, H. C., Debebe, J., Ball, J., Chappell, J., Khakh, M., Carlile, M., Loose, M., Lister, M. M., Holmes, N., Tsoleridis, T., Fleming, V. M., Wright, V., Smith, W., Gallagher, M. D., Parker, M., Partridge, D. G., Evans, C., Baker, P., Essex, S., Liggett, S., Keeley, A. J., Bashton, M., Rooke, S., Dervisavic, S., Meader, E. J., Lopez, C. E. B., Angyal, A., Kristiansen, M., Tutill, H. J., Findlay, J., Mestek-Boukhibar, L., Forrest, L., Dyal, P., Williams, R. J., Panchbhaya, Y., Williams, C. A., Roy, S., Pandey, S., Stockton, J., Loman, N. J., Poplawski, R., Nicholls, S., Rowe, W. P. M., Khokhar, F., Pinckert, M. L., Hosmillo, M., Chaudhry, Y., Caller, L. G., Davidson, R. K., Griffith, L., Rambaut, A., Jackson, B., Colquhoun, R., Hill, V., Nichols, J., Asamaphan, P., Darby, A., Jackson, K. A., Iturriza-Gomara, M., Vamos, E. E., Green, A., Aanensen, D., Bonsall, D., Buck, D., Macintyre-Cockett, G., de Cesare, M., Pybus, O., Golubchik, T., Scarlett, G., Loveson, K. F., Robson, S. C., Beckett, A., Lindsey, B., Groves, D. C., Parsons, P. J., Mchugh, M. P., Barnes, J. D., Manso, C. F., Grammatopoulos, D., Menger, K. E., Harrison, E., Gunson, R., Peacock, S. J., Gonzalez, G., Carr, M., Mihaela, L., Popovici, O., Brytting, M., Bresner, C., Fuller, W., Workman, T., Mentis, A. F., Kossyvakis, A., Karamitros, T., Pogka, V., Kalliaropoulos, A., Horefti, E., Kontou, A., Martinez-Gonzalez, B., Labropoulou, V., Voulgari-Kokota, A., Evangelidou, M., Bizta, P., Belimezi, M., Lambrechts, L., Doymaz, M. Z., Yazici, M. K., Cetin, N. S., Karaaslan, E., Kallio-Kokko, H., Virtanen, J., Suvanto, M., Nguyen, P. T., Ellonen, P., Hannula, S., Kangas, H., Sreenu, V. B., Burian, K., Terhes, G., Gombos, K., Gyenesei, A., Urban, P., Herczeg, R., Jakab, F., Kemenesi, G., Toth, G. E., Somogyi, B., Zana, B., Zeghbib, S., Kuczmog, A., Foldes, F., Lanszki, Z., Madai, M., Papp, H., Pereszlenyi, C. I., Babinszky, G. C., Dudas, G., Csoma, E., Abou Tayoun, A. N., Alsheikh-Ali, A. A., Loney, T., Nowotny, N., Abdul-Wahab, O., Gonzalez-Candelas, F., Andersen, M. H., Taylor, S., European Centre for Disease Prevention and Control (ECDC), Public Health Wales Microbiology Cardiff, Faculty of Agriculture and Forestry, Department of Agricultural Sciences, and Institute of Biotechnology

Subjects
Infecções Respiratórias, 0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], Distribution (economics), Wastewater, MESH: Base Sequence, Severe Acute Respiratory Syndrome, MESH: World Health Organization, Pandemic, MESH: Coronavirus, MESH: COVID-19, Sequencing, Viral, Clade, Nomenclature, Genome, biology, COVID-19, Europe, NGS, SARS-CoV-2, WGS, nomenclature, sequencing, Base Sequence, Betacoronavirus, Coronavirus, Coronavirus Infections, Genome, Viral, Humans, Phylogeography, Pneumonia, Viral, RNA, Viral, RNA-Dependent RNA Polymerase, Spatio-Temporal Analysis, World Health Organization, Pandemics, C500, European region, 3. Good health, Geography, MESH: Phylogeography, MESH: RNA-Dependent RNA Polymerase, MESH: RNA, Viral, MESH: Betacoronavirus, Spatio-Temporal Analysi, MESH: Genome, Viral, Cartography, Human, Bioquímica, MESH: Pandemics, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronaviru, 030106 microbiology, 03 medical and health sciences, MESH: Spatio-Temporal Analysis, MESH: Severe Acute Respiratory Syndrome, Virology, MESH: SARS-CoV-2, Whole genome sequencing, MESH: Humans, Whole Genome Sequencing, Betacoronaviru, Coronavirus Infection, business.industry, Public Health, Environmental and Occupational Health, Pneumonia, biology.organism_classification, B900, 030104 developmental biology, MESH: Pneumonia, Viral, RNA, SARS_CoV-2, 3111 Biomedicine, MESH: Europe, Human medicine, business
Abstract

8 páginas, 3 figuras, We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2., We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible.

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31. Molecular detection of Bartonella spp. in deer ked pupae, adult keds and moose blood in Finland

Author

KORHONEN, E. M., PÉREZ VERA, C., PULLIAINEN, A.T., SIRONEN, T., AALTONEN, K., KORTET, R., HÄRKÖNEN, L., HÄRKÖNEN, S., PAAKKONEN, T., NIEMINEN, P., MUSTONEN, A-M, YLÖNEN, H., VAPALAHTI, O., KORHONEN, E. M., PÉREZ VERA, C., PULLIAINEN, A.T., SIRONEN, T., AALTONEN, K., KORTET, R., HÄRKÖNEN, L., HÄRKÖNEN, S., PAAKKONEN, T., NIEMINEN, P., MUSTONEN, A-M, YLÖNEN, H., and VAPALAHTI, O.

Abstract

The deer ked (Lipoptena cervi) is a haematophagous ectoparasite of cervids that harbours haemotrophic Bartonella. A prerequisite for the vector competence of the deer ked is the vertical transmission of the pathogen from the mother to its progeny and transstadial transmission from pupa to winged adult. We screened 1154 pupae and 59 pools of winged adult deer keds from different areas in Finland for Bartonella DNA using PCR. Altogether 13 pupa samples and one winged adult deer ked were positive for the presence of Bartonella DNA. The amplified sequences were closely related to either B. schoenbuchensis or B. bovis. The same lineages were identified in eight blood samples collected from free-ranging moose. This is the first demonstration of Bartonella spp. DNA in a winged adult deer ked and, thus, evidence for potential transstadial transmission of Bartonella spp. in the species

32. Young male patients are at elevated risk of developing serious central nervous system complications during acute Puumala hantavirus infection

Author

Hautala Timo, Hautala Nina, Mähönen Saara-Mari, Sironen Tarja, Pääkkö Eija, Karttunen Ari, Salmela Pasi I, Vainio Olli, Rytky Seppo, Plyusnin Alexander, Vaheri Antti, Vapalahti Olli, and Kauma Heikki

Subjects
hantavirus, encephalitis, hypopituitarism, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Our aim was to characterize clinical properties and laboratory parameters in patients with or without cerebrospinal fluid (CSF) findings suggestive of central nervous system (CNS) involvement, and especially those who developed serious CNS complications during acute nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) infection. Methods A prospective cohort of 40 patients with acute NE and no signs of major CNS complications was analyzed. In addition, 8 patients with major CNS complications associated with NE were characterized. We collected data of CNS symptoms, CSF analysis, brain magnetic resonance imaging (MRI) results, electroencephalography (EEG) recordings, kidney function, and a number of laboratory parameters. Selected patients were evaluated by an ophthalmologist. Results Patients with a positive CSF PUUV IgM finding or major CNS complications were more often males (p < 0.05) and they had higher plasma creatinine values (p < 0.001) compared to those with negative CSF PUUV IgM. The degree of tissue edema did not explain the CSF findings. Patients with major CNS complications were younger than those with negative CSF PUUV IgM finding (52.9 vs. 38.5 years, p < 0.05). Some patients developed permanent neurological and ophthalmological impairments. Conclusions CNS and ocular involvement during and after acute NE can cause permanent damage and these symptoms seem to be attributable to true infection of the CNS rather than increased tissue permeability. The possibility of this condition should be borne in mind especially in young male patients.

Published
2011
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33. Concomitant influence of helminth infection and landscape on the distribution of Puumala hantavirus in its reservoir, Myodes glareolus

Author

Henttonen Heikki, Voutilainen Liina, Sironen Tarja, Poulle Marie-Lazarine, Cadet Patrice, Chaval Yannick, Xuéreb Anne, Guivier Emmanuel, Salvador Alexis, Cosson Jean-François, and Charbonnel Nathalie

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Puumala virus, the agent of nephropathia epidemica (NE), is the most prevalent hantavirus in Europe. The risk for human infection seems to be strongly correlated with the prevalence of Puumala virus (PUUV) in populations of its reservoir host species, the bank vole Myodes glareolus. In humans, the infection risks of major viral diseases are affected by the presence of helminth infections. We therefore proposed to analyse the influence of both helminth community and landscape on the prevalence of PUUV among bank vole populations in the Ardennes, a PUUV endemic area in France. Results Among the 313 voles analysed, 37 had anti-PUUV antibodies. Twelve gastro-intestinal helminth species were recorded among all voles sampled. We showed that PUUV seroprevalence strongly increased with age or sexual maturity, especially in the northern forests (massif des Ardennes). The helminth community structure significantly differed between this part and the woods or hedgerows of the southern cretes pre-ardennaises. Using PUUV RNA quantification, we identified significant coinfections between PUUV and gastro-intestinal helminths in the northern forests only. More specifically, PUUV infection was positively associated with the presence of Heligmosomum mixtum, and in a lesser extent, Aonchotheca muris-sylvatici. The viral load of PUUV infected individuals tended to be higher in voles coinfected with H. mixtum. It was significantly lower in voles coinfected with A. muris-sylvatici, reflecting the influence of age on these latter infections. Conclusions This is the first study to emphasize hantavirus - helminth coinfections in natural populations. It also highlights the importance to consider landscape when searching for such associations. We have shown that landscape characteristics strongly influence helminth community structure as well as PUUV distribution. False associations might therefore be evidenced if geographic patterns of helminths or PUUV repartition are not previously identified. Moreover, our work revealed that interactions between helminths and landscape enhance/deplete the occurrence of coinfections between PUUV and H. mixtum or A. muris-sylvatici. Further experimental analyses and long-term individual surveys are now required to confirm these correlative results, and to ascertain the causal links between helminth and PUUV infection risks.

Published
2011
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34. Orthomyxo-, paramyxo- and flavivirus infections in wild waterfowl in Finland

Author

Pöysä Hannu, Huhtamo Eili, Sironen Tarja, Ek-Kommonen Christine, Rätti Osmo, Huovilainen Anita, Lindh Erika, Vaheri Antti, and Vapalahti Olli

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Screening wild birds for viral pathogens has become increasingly important. We tested a screening approach based on blood and cloacal and tracheal swabs collected by hunters to study the prevalence of influenza A, paramyxo-, flavi-, and alphaviruses in Finnish wild waterfowl, which has been previously unknown. We studied 310 blood samples and 115 mixed tracheal and cloacal swabs collected from hunted waterfowl in 2006. Samples were screened by RT-PCR and serologically by hemagglutination inhibition (HI) test or enzyme-linked immunosorbent assay (ELISA) for influenza A (FLUAV), type 1 avian paramyxo-(APMV-1), Sindbis (SINV), West Nile (WNV) and tick-borne encephalitis (TBEV) virus infections. Results FLUAV RNA was found in 13 tracheal/cloacal swabs and seven strains were isolated. Five blood samples were antibody positive. Six APMV-1 RNA-positive samples were found from which four strains were isolated, while two blood samples were antibody positive. None of the birds were positive for flavivirus RNA but three birds had flavivirus antibodies by HI test. No antibodies to SINV were detected. Conclusion We conclude that circulation of both influenza A virus and avian paramyxovirus-1 in Finnish wild waterfowl was documented. The FLUAV and APMV-1 prevalences in wild waterfowl were 11.3% and 5.2% respectively, by this study. The subtype H3N8 was the only detected FLUAV subtype while APMV-1 strains clustered into two distinct lineages. Notably, antibodies to a likely mosquito-borne flavivirus were detected in three samples. The screening approach based on hunted waterfowl seemed reliable for monitoring FLUAV and APMV by RT-PCR from cloacal or tracheal samples, but antibody testing in this format seemed to be of low sensitivity.

Published
2008
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35. Phylogenetic evidence for the distinction of Saaremaa and Dobrava hantaviruses

Author

Plyusnin Alexander, Vaheri Antti, and Sironen Tarja

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Dobrava virus (DOBV) and Saaremaa virus (SAAV) are two closely related hantaviruses carried by different rodent species. The distinction of these two viruses has been a matter of debate. While the phylogenies based on the viral M segment sequences were repeatedly showing monophyly of SAAV strains, some trees based on the S segment sequences were not, thus causing questions on the demarcation between these two viruses. In order to clarify this issue, the current collection of the virus S segment sequences was subjected to extensive phylogenetic analysis using maximum likelihood, maximum parsimony and distant matrix methods. In all inferred phylogenies, the SAAV sequences were monophyletic and separated from DOBV sequences, thus supporting the view that SAAV and DOBV are distinct hantavirus species. Since collection of the S segment sequences used in this study "obeyed" the molecular clock, calculations of the split of DOBV and SAAV were now repeated resulting in an estimation of 3.0–3.7 MYA that is very close to the values obtained earlier.

Published
2005
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37. Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.

Author

Hunt M, Hinrichs AS, Anderson D, Karim L, Dearlove BL, Knaggs J, Constantinides B, Fowler PW, Rodger G, Street T, Lumley S, Webster H, Sanderson T, Ruis C, Kotzen B, de Maio N, Amenga-Etego LN, Amuzu DSY, Avaro M, Awandare GA, Ayivor-Djanie R, Barkham T, Bashton M, Batty EM, Bediako Y, Belder D, Benedetti E, Bergthaler A, Boers SA, Campos J, Carr RAA, Chen YYC, Cuba F, Dattero ME, Dejnirattisai W, Dilthey A, Duedu KO, Endler L, Engelmann I, Francisco NM, Fuchs J, Gnimpieba EZ, Groc S, Gyamfi J, Heemskerk D, Houwaart T, Hsiao NY, Huska M, Hölzer M, Iranzadeh A, Jarva H, Jeewandara C, Jolly B, Joseph R, Kant R, Ki KKK, Kurkela S, Lappalainen M, Lataretu M, Lemieux J, Liu C, Malavige GN, Mashe T, Mongkolsapaya J, Montes B, Mora JAM, Morang'a CM, Mvula B, Nagarajan N, Nelson A, Ngoi JM, da Paixão JP, Panning M, Poklepovich T, Quashie PK, Ranasinghe D, Russo M, San JE, Sanderson ND, Scaria V, Screaton G, Sessions OM, Sironen T, Sisay A, Smith D, Smura T, Supasa P, Suphavilai C, Swann J, Tegally H, Tegomoh B, Vapalahti O, Walker A, Wilkinson RJ, Williamson C, Zair X, de Oliveira T, Peto TE, Crook D, Corbett-Detig R, and Iqbal Z

Abstract

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 4,471,579 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of June 2024, viewable at https://viridian.taxonium.org . Each genome was constructed using a novel assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

Published
2024
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38. Author Correction: Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance.

Author

Becsei Á, Fuschi A, Otani S, Kant R, Weinstein I, Alba P, Stéger J, Visontai D, Brinch C, de Graaf M, Schapendonk CME, Battisti A, De Cesare A, Oliveri C, Troja F, Sironen T, Vapalahti O, Pasquali F, Bányai K, Makó M, Pollner P, Merlotti A, Koopmans M, Csabai I, Remondini D, Aarestrup FM, and Munk P

Published
2024
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39. Potentially zoonotic pathogens and parasites in opportunistically sourced urban brown rats ( Rattus norvegicus ) in and around Helsinki, Finland, 2018 to 2023.

Author

Aivelo T, Alburkat H, Suomalainen N, Kukowski R, Heikkinen P, Oksanen A, Huitu O, Kivistö R, and Sironen T

Subjects
Animals, Rats, Finland epidemiology, Humans, Parasites isolation & purification, Parasites classification, Helminths isolation & purification, Rodent Diseases epidemiology, Rodent Diseases parasitology, Rodent Diseases virology, Prevalence, Parasitic Diseases, Animal epidemiology, Parasitic Diseases, Animal parasitology, Zoonoses
Abstract

BackgroundBrown rats ( Rattus norvegicus ) are synanthropic rodents with worldwide distribution, which are known to harbour many zoonotic pathogens and parasites. No systematic zoonotic surveys targeting multiple pathogens and parasites have previously been conducted in urban rats in Finland.AimIn Helsinki, Finland, we explored the presence and prevalence in brown rats of certain pathogens and parasites (including helminths, viruses and bacteria) across potentially zoonotic taxa.MethodsWe opportunistically received rat carcasses from pest management operators and citizens from 2018 to 2023. We searched for heart- or lungworms, performed rat diaphragm digestion to check for Trichinella and morphologically identified intestinal helminths. We assessed virus exposure by immunofluorescence assay or PCR, and detected bacteria by PCR ( Leptospira ) or culture ( Campylobacter ).ResultsAmong the rats investigated for helminths, no heart- or lungworms or Trichinella species were detected and the most common finding was the cestode Hymenolepis nana (in 9.7% of individuals sampled, 28/288). For some of the surveyed virus taxa, several rats were seropositive (orthopoxviruses, 5.2%, 11/211; arenaviruses, 2.8%, 6/211; hantaviruses 5.2%, 11/211) or tested positive by PCR (rat hepatitis E virus, 1.8%, 4/216). Campylobacter jejuni (6.6%, 17/259) and Leptospira interrogans (1.2%, 2/163) bacteria were also present in the rat population examined.ConclusionsPrevalences of potentially zoonotic pathogens and parasites in brown rats in Helsinki appeared low. This may explain low or non-existent diagnosis levels of rat-borne pathogen and parasite infections reported in people there. Nevertheless, further assessment of under-diagnosis, which cannot be excluded, would enhance understanding the risks of zoonoses.

Published
2024
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40. Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance.

Author

Becsei Á, Fuschi A, Otani S, Kant R, Weinstein I, Alba P, Stéger J, Visontai D, Brinch C, de Graaf M, Schapendonk CME, Battisti A, De Cesare A, Oliveri C, Troja F, Sironen T, Vapalahti O, Pasquali F, Bányai K, Makó M, Pollner P, Merlotti A, Koopmans M, Csabai I, Remondini D, Aarestrup FM, and Munk P

Subjects
Humans, Europe, Sewage microbiology, Metagenomics methods, Seasons, Microbiota genetics, Bacteria genetics, Bacteria classification, Bacteria isolation & purification, Metagenome genetics
Abstract

Sewage metagenomics has risen to prominence in urban population surveillance of pathogens and antimicrobial resistance (AMR). Unknown species with similarity to known genomes cause database bias in reference-based metagenomics. To improve surveillance, we seek to recover sewage genomes and develop a quantification and correlation workflow for these genomes and AMR over time. We use longitudinal sewage sampling in seven treatment plants from five major European cities to explore the utility of catch-all sequencing of these population-level samples. Using metagenomic assembly methods, we recover 2332 metagenome-assembled genomes (MAGs) from prokaryotic species, 1334 of which were previously undescribed. These genomes account for ~69% of sequenced DNA and provide insight into sewage microbial dynamics. Rotterdam (Netherlands) and Copenhagen (Denmark) show strong seasonal microbial community shifts, while Bologna, Rome, (Italy) and Budapest (Hungary) have occasional blooms of Pseudomonas-dominated communities, accounting for up to ~95% of sample DNA. Seasonal shifts and blooms present challenges for effective sewage surveillance. We find that bacteria of known shared origin, like human gut microbiota, form communities, suggesting the potential for source-attributing novel species and their ARGs through network community analysis. This could significantly improve AMR tracking in urban environments., (© 2024. The Author(s).)

Published
2024
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41. The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.

Author

Cabrera LE, Jokiranta ST, Mäki S, Miettinen S, Kant R, Kareinen L, Sironen T, Pietilä JP, Kantele A, Kekäläinen E, Lindgren H, Mattila P, Kipar A, Vapalahti O, and Strandin T

Subjects
Humans, Animals, Mice, Male, Female, Middle Aged, Immunity, Innate, Adult, Mice, Inbred C57BL, COVID-19 immunology, Neutrophils immunology, Neutrophils metabolism, Interferon Type I metabolism, Interferon Type I immunology, Inflammasomes immunology, Inflammasomes metabolism, SARS-CoV-2 immunology
Abstract

The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cabrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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42. Bat humoral immunity and its role in viral pathogenesis, transmission, and zoonosis.

Author

Roffler AA, Maurer DP, Lunn TJ, Sironen T, Forbes KM, and Schmidt AG

Subjects
Animals, Humans, Adaptive Immunity immunology, Chiroptera virology, Chiroptera immunology, Immunity, Humoral, Antibodies, Viral immunology, Zoonoses immunology, Zoonoses transmission, Zoonoses virology
Abstract

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat's innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Roffler, Maurer, Lunn, Sironen, Forbes and Schmidt.)

Published
2024
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43. Wild red foxes ( Vulpes vulpes ) do not participate in SARS-CoV-2 circulation in Poland.

Author

Goll A, Krupińska M, Nowicka J, Baranowicz K, Rabalski L, Lass A, Gorska A, Sironen T, Kant R, and Grzybek M

Abstract

Background: Biomonitoring is an essential activity for identifying possible vectors and reservoirs of pathogens and predicting potential outbreaks. Wild red foxes are present in both sylvatic and synanthropic environments, making them potential carriers of zoonotic pathogens. Experimental studies have shown that both coyotes and red foxes can transmit SARS-CoV-2. This study aimed to assess the prevalence and seroprevalence of SARS-CoV-2 in wild red foxes hunted in northern Poland., Methods: Oral swabs, blood clots or heat tissue samples were collected from 292 red foxes hunted in northern Poland. We used both molecular (RT-PCR) and serological (IFA) approaches to detect SARS-CoV-2 infections in the sampled animals., Results: We did not find any evidence of SARS-CoV-2 infection in the collected samples, using both molecular and serological methods., Conclusions: Despite foxes having frequent contact with humans, human waste, and other animals, they do not appear to participate in the circulation of the SARS-CoV-2 virus in our geographical region. Nevertheless, we believe that continuous biomonitoring should be performed to assess the SARS-CoV-2 epidemiological situation in the wild., Competing Interests: None., (© 2024 The Authors.)

Published
2024
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44. Highly pathogenic avian influenza A(H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023.

Author

Kareinen L, Tammiranta N, Kauppinen A, Zecchin B, Pastori A, Monne I, Terregino C, Giussani E, Kaarto R, Karkamo V, Lähteinen T, Lounela H, Kantala T, Laamanen I, Nokireki T, London L, Helve O, Kääriäinen S, Ikonen N, Jalava J, Kalin-Mänttäri L, Katz A, Savolainen-Kopra C, Lindh E, Sironen T, Korhonen EM, Aaltonen K, Galiano M, Fusaro A, and Gadd T

Subjects
Animals, Finland epidemiology, Farms, Orthomyxoviridae Infections veterinary, Orthomyxoviridae Infections virology, Orthomyxoviridae Infections mortality, Orthomyxoviridae Infections epidemiology, Foxes virology, Birds virology, Mink virology, Influenza in Birds virology, Influenza in Birds epidemiology, Phylogeny, Influenza A Virus, H5N1 Subtype genetics, Influenza A Virus, H5N1 Subtype pathogenicity, Influenza A Virus, H5N1 Subtype isolation & purification, Animals, Wild virology, Charadriiformes virology, Disease Outbreaks veterinary
Abstract

Highly pathogenic avian influenza (HPAI) has caused widespread mortality in both wild and domestic birds in Europe 2020-2023. In July 2023, HPAI A(H5N1) was detected on 27 fur farms in Finland. In total, infections in silver and blue foxes, American minks and raccoon dogs were confirmed by RT-PCR. The pathological findings in the animals include widespread inflammatory lesions in the lungs, brain and liver, indicating efficient systemic dissemination of the virus. Phylogenetic analysis of Finnish A(H5N1) strains from fur animals and wild birds has identified three clusters (Finland I-III), and molecular analyses revealed emergence of mutations known to facilitate viral adaptation to mammals in the PB2 and NA proteins. Findings of avian influenza in fur animals were spatially and temporally connected with mass mortalities in wild birds. The mechanisms of virus transmission within and between farms have not been conclusively identified, but several different routes relating to limited biosecurity on the farms are implicated. The outbreak was managed in close collaboration between animal and human health authorities to mitigate and monitor the impact for both animal and human health.

Published
2024
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45. Evolution and genetic characterization of Seoul virus in wild rats Rattus norvegicus from an urban park in Lyon, France 2020-2022.

Author

Alburkat H, Smura T, Bouilloud M, Pradel J, Anfray G, Berthier K, Dutra L, Loiseau A, Niamsap T, Olander V, Sepulveda D, Venkat V, Charbonnel N, Castel G, and Sironen T

Subjects
Animals, Rats virology, France epidemiology, Animals, Wild virology, Humans, Cities epidemiology, Rodent Diseases virology, Rodent Diseases epidemiology, Seoul virus genetics, Seoul virus isolation & purification, Seoul virus classification, Phylogeny, Hemorrhagic Fever with Renal Syndrome epidemiology, Hemorrhagic Fever with Renal Syndrome virology, Hemorrhagic Fever with Renal Syndrome veterinary, Hemorrhagic Fever with Renal Syndrome transmission, Parks, Recreational
Abstract

Background: Seoul virus (SEOV) is an orthohantavirus primarily carried by rats. In humans, it may cause hemorrhagic fever with renal syndrome (HFRS). Its incidence is likely underestimated and given the expansion of urban areas, a better knowledge of SEOV circulation in rat populations is called for. Beyond the need to improve human case detection, we need to deepen our comprehension of the ecological, epidemiological, and evolutionary processes involved in the transmission of SEOV., Methodology / Principal Findings: We performed a comprehensive serological and molecular characterization of SEOV in Rattus norvegicus in a popular urban park within a large city (Lyon, France) to provide essential information to design surveillance strategies regarding SEOV. We sampled rats within the urban park of 'La Tête d'Or' in Lyon city from 2020 to 2022. We combined rat population genetics, immunofluorescence assays, SEOV high-throughput sequencing (S, M, and L segments), and phylogenetic analyses. We found low structuring of wild rat populations within Lyon city. Only one sampling site within the park (building created in 2021) showed high genetic differentiation and deserves further attention. We confirmed the circulation of SEOV in rats from the park with high seroprevalence (17.2%) and high genetic similarity with the strain previously described in 2011 in Lyon city., Conclusion/significance: This study confirms the continuous circulation of SEOV in a popular urban park where the risk for SEOV transmission to humans is present. Implementing a surveillance of this virus could provide an efficient early warning system and help prepare risk-based interventions. As we reveal high gene flow between rat populations from the park and the rest of the city, we advocate for SEOV surveillance to be conducted at the scale of the entire city., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alburkat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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46. Transmission of drug-resistant Mycobacterium tuberculosis isolates between Finnish- and foreign-born cases, 2014-2021: A molecular epidemiological study.

Author

Zhu J, Haanpera M, Mentula S, Vapalahti O, Soini H, Sironen T, Kant R, and Zakham F

Subjects
Humans, Antitubercular Agents therapeutic use, Finland epidemiology, Molecular Epidemiology, Genotype, Mycobacterium tuberculosis genetics, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis microbiology
Abstract

Background: Data on the molecular epidemiology and transmission of drug-resistant Mycobacterium tuberculosis (MTB) in low-incidence settings with immigration from high-incidence settings is limited., Method: We included 115 drug-resistant (DR) MTB isolates with whole-genome sequencing data isolated in Finland between 2014 and 2021. Potential transmission clusters were identified using a threshold of 12 single-nucleotide polymorphisms (SNPs). Highly related clusters were identified using a threshold of 5 SNPs., Result: Of the 115 DR MTB isolates, 31 (27.0%) isolates were from Finnish-born cases and 84 (73.0%) were from foreign-born cases. The proportion of multidrug-resistant (MDR) MTB isolates (30/84, 35.7%) from foreign-born cases was higher than that of MDR MTB isolates from Finnish-born cases (8/31, 25.8%). Lineage 2 (40/115, 34.8%) and lineage 4 (40/115, 34.8%) were the most prevalent lineages. A total of 25 (21.7%) isolates were classified into eight potential transmission clusters (≤12 SNPs). Furthermore, five highly related clusters (≤5 SNPs) were identified, including three DR MTB isolates from Finnish-born cases and 14 DR isolates from foreign-born cases., Conclusion: The risk of DR MTB transmission between Finnish- and foreign-born persons is not negligible. Further research on clustering analysis in drug-susceptible MTB is worth to inform tuberculosis management and control in low-incidence settings with increasing immigration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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47. Hibernating vesper bats are a weak source for biomonitoring of coronaviruses.

Author

Goll A, Dutra L, Nowicka J, Sgarabotto E, Venkat V, Apoznański G, Kokurewicz T, Rachwald A, Rabalski L, Alburkat H, Virtanen J, Sironen T, Kant R, Bourret V, and Grzybek M

Abstract

Background: Our study explores the role of bats as reservoirs of coronaviruses., Methods: We conducted virological screening of bats hibernating in military bunkers at the Natura 2000 site "Nietoperek" in Western Poland collecting oral and anal swab samples from 138 bats across six species to apply a combination of pan-coronavirus and SARS-CoV-2 specific PCR assays., Results: Only one anal swab tested positive for coronavirus. No SARS-CoV-2 was detected in any of the samples. The low prevalence of coronavirus in the studied colony contrasts with higher rates found in other regions and may be influenced by hibernation., Conclusions: Hibernating bats may show a low prevalence of coronavirus, potentially due to the hibernation process itself. This finding indicates that hibernating bats may not be the most optimal subjects for screening zoonotic pathogens. However, biomonitoring of bats for emerging and reemerging diseases is recommended for comprehensive epidemiological insights., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maciej Grzybek reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s). Published by Elsevier B.V.)

Published
2024
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48. Nanobody engineering for SARS-CoV-2 neutralization and detection.

Author

Hannula L, Kuivanen S, Lasham J, Kant R, Kareinen L, Bogacheva M, Strandin T, Sironen T, Hepojoki J, Sharma V, Saviranta P, Kipar A, Vapalahti O, Huiskonen JT, and Rissanen I

Subjects
Humans, SARS-CoV-2 genetics, Pandemics, Antibodies, Neutralizing, Antibodies, Viral, COVID-19 diagnosis, Single-Domain Antibodies genetics, Spike Glycoprotein, Coronavirus
Abstract

In response to the ongoing COVID-19 pandemic, the quest for coronavirus inhibitors has inspired research on a variety of small proteins beyond conventional antibodies, including robust single-domain antibody fragments, i.e., "nanobodies." Here, we explore the potential of nanobody engineering in the development of antivirals and diagnostic tools. Through fusion of nanobody domains that target distinct binding sites, we engineered multimodular nanobody constructs that neutralize wild-type SARS-CoV-2 and the Alpha and Delta variants at high potency, with IC 50 values as low as 50 pM. Despite simultaneous binding to distinct epitopes, Beta and Omicron variants were more resistant to neutralization by the multimodular nanobodies, which highlights the importance of accounting for antigenic drift in the design of biologics. To further explore the applications of nanobody engineering in outbreak management, we present an assay based on fusions of nanobodies with fragments of NanoLuc luciferase that can detect sub-nanomolar quantities of the SARS-CoV-2 spike protein in a single step. Our work showcases the potential of nanobody engineering to combat emerging infectious diseases., Importance: Nanobodies, small protein binders derived from the camelid antibody, are highly potent inhibitors of respiratory viruses that offer several advantages over conventional antibodies as candidates for specific therapies, including high stability and low production costs. In this work, we leverage the unique properties of nanobodies and apply them as building blocks for new therapeutic and diagnostic tools. We report ultra-potent SARS-CoV-2 inhibition by engineered nanobodies comprising multiple modules in structure-guided combinations and develop nanobodies that carry signal molecules, allowing rapid detection of the SARS-CoV-2 spike protein. Our results highlight the potential of engineered nanobodies in the development of effective countermeasures, both therapeutic and diagnostic, to manage outbreaks of emerging viruses., Competing Interests: The authors declare no conflict of interest.

Published
2024
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49. Phylogenetic Characterization of Orthohantavirus dobravaense (Dobrava Virus).

Author

Erdin M, Polat C, Smura T, Irmak S, Cetintas O, Cogal M, Colak F, Karatas A, Sozen M, Matur F, Vapalahti O, Sironen T, and Oktem IMA

Subjects
Phylogeny, Cluster Analysis, Public Health, Orthohantavirus, RNA Viruses
Abstract

We report complete coding sequences of Orthohantavirus dobravaense (Dobrava virus) Igneada strains and phylogenetic characterization of all available complete coding sequences. Our analyses suggested separation of host-dependent lineages, followed by geographic clustering. Surveillance of orthohantaviruses using complete genomes would be useful for assessing public health threats from Dobrava virus.

Published
2024
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50. SARS-CoV-2 infections among pregnant women, 2020, Finland-Cross-testing of neutralization assays.

Author

Virtanen J, Korhonen EM, Salonen S, Vapalahti O, Sironen T, and Jääskeläinen AJ

Subjects
Pregnancy, Humans, Female, SARS-CoV-2, Pregnant Women, Retrospective Studies, Seroepidemiologic Studies, Finland epidemiology, COVID-19 Testing, Clinical Laboratory Techniques methods, Sensitivity and Specificity, Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G, COVID-19 diagnosis, COVID-19 epidemiology
Abstract

We studied the development of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) pandemic in southern Finland in 2020 and evaluated the performance of two surrogate immunoassays for the detection of neutralizing antibodies (NAbs). The data set consisted of 12 000 retrospectively collected samples from pregnant women in their first trimester throughout 2020. All the samples were initially screened for immunoglobulin G (IgG) with SARS-CoV-2 spike antibody assay (EIM-S1, Euroimmun) followed by confirmation with nucleocapsid antibody assay (Architect SARS-CoV-2, Abbott). Samples that were reactive (positive or borderline) with both assays were subjected to testing with commercial surrogate immunoassays of NeutraLISA (EIM) and cPass TM (GenScript Biotech Corporation) by using pseudoneutralization assay (PNAbA) as a golden standard. No seropositive cases were detected between January and March. Between April and December, IgG (EIM-S1 and Abbott positive) and NAb (PNAbA positive) seroprevalences were between 0.4% and 1.4%. NeutraLISA showed 90% and cPass 55% concordant results with PNAbA among PNAbA negative samples and 49% and 92% among PNAbA positive samples giving NeutraLISA better specificity but lower sensitivity than cPass. To conclude, seroprevalence in pregnant women reflected that of the general population but the variability of the performance of serological protocols needs to be taken into account in inter-study comparison., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Published
2024
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