{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:13:30Z","timestamp":1760235210659,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KI2016","031L0176A"],"award-info":[{"award-number":["01KI2016","031L0176A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bundesministerium fuer Gesundheit","award":["DESH"],"award-info":[{"award-number":["DESH"]}]},{"DOI":"10.13039\/100008662","name":"Joachim Herz Stiftung","doi-asserted-by":"publisher","award":["Add-on fellowship for interdisciplinary life science"],"award-info":[{"award-number":["Add-on fellowship for interdisciplinary life science"]}],"id":[{"id":"10.13039\/100008662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Here, we report on the increasing frequency of the SARS-CoV-2 lineage A.27 in Germany during the first months of 2021. Genomic surveillance identified 710 A.27 genomes in Germany as of 2 May 2021, with a vast majority identified in laboratories from a single German state (Baden-Wuerttemberg, n = 572; 80.5%). Baden-Wuerttemberg is located near the border with France, from where most A.27 sequences were entered into public databases until May 2021. The first appearance of this lineage based on sequencing in a laboratory in Baden-Wuerttemberg can be dated to early January \u201921. From then on, the relative abundance of A.27 increased until the end of February but has since declined\u2014meanwhile, the abundance of B.1.1.7 increased in the region. The A.27 lineage shows a mutational pattern typical of VOIs\/VOCs, including an accumulation of amino acid substitutions in the Spike glycoprotein. Among those, L18F, L452R and N501Y are located in the epitope regions of the N-terminal- (NTD) or receptor binding domain (RBD) and have been suggested to result in immune escape and higher transmissibility. In addition, A.27 does not show the D614G mutation typical for all VOIs\/VOCs from the B lineage. Overall, A.27 should continue to be monitored nationally and internationally, even though the observed trend in Germany was initially displaced by B.1.1.7 (Alpha), while now B.1.617.2 (Delta) is on the rise.<\/jats:p>","DOI":"10.3390\/v13081491","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T21:21:21Z","timestamp":1627593681000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rise and Fall of SARS-CoV-2 Lineage A.27 in Germany"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-0509","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Calvignac-Spencer","sequence":"first","affiliation":[{"name":"Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-515X","authenticated-orcid":false,"given":"Matthias","family":"Budt","sequence":"additional","affiliation":[{"name":"Influenza and other Respiratory Viruses, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0912-745X","authenticated-orcid":false,"given":"Matthew","family":"Huska","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Bioinformatics, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-1340","authenticated-orcid":false,"given":"Hugues","family":"Richard","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Bioinformatics, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-1240","authenticated-orcid":false,"given":"Luca","family":"Leipold","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Information and Research Data Management, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9300-6625","authenticated-orcid":false,"given":"Linus","family":"Grabenhenrich","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Information and Research Data Management, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-7267","authenticated-orcid":false,"given":"Torsten","family":"Semmler","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Genome Sequencing and Genomic Epidemiology, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6394","authenticated-orcid":false,"given":"Max","family":"von Kleist","sequence":"additional","affiliation":[{"name":"Systems Medicine of Infectious Disease, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-4798","authenticated-orcid":false,"given":"Stefan","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"Infectious Disease Epidemiology, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-236X","authenticated-orcid":false,"given":"Thorsten","family":"Wolff","sequence":"additional","affiliation":[{"name":"Influenza and other Respiratory Viruses, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-8717","authenticated-orcid":false,"given":"Martin","family":"H\u00f6lzer","sequence":"additional","affiliation":[{"name":"Methodology and Research Infrastructure, Bioinformatics, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1093\/bib\/bbaa232","article-title":"Computational strategies to combat COVID-19: Useful tools to accelerate SARS-CoV-2 and coronavirus research","volume":"22","author":"Hufsky","year":"2021","journal-title":"Briefings Bioinform."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"COG-UK (2020). An integrated national scale SARS-CoV-2 genomic surveillance network. Lancet Microbe, 1, e99.","DOI":"10.1016\/S2666-5247(20)30054-9"},{"key":"ref_3","first-page":"388","article-title":"SARS-CoV-2-Varianten: Evolution im Zeitraffer","volume":"118","author":"Oh","year":"2021","journal-title":"Dtsch. Arztebl."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vavrek, D., Speroni, L., Curnow, K.J., Oberholzer, M., Moeder, V., and Febbo, P.G. (2021). Genomic surveillance at scale is required to detect newly emerging strains at an early timepoint. medRxiv.","DOI":"10.1101\/2021.01.12.21249613"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.chom.2020.11.007","article-title":"Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition","volume":"29","author":"Greaney","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, Y., Liu, J., Plante, K.S., Plante, J.A., Xie, X., Zhang, X., Ku, Z., An, Z., Scharton, D., and Schindewolf, C. (2021). The N501Y spike substitution enhances SARS-CoV-2 transmission. BioRxiv.","DOI":"10.1101\/2021.03.08.434499"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Deng, X., Garcia-Knight, M.A., Khalid, M.M., Servellita, V., Wang, C., Morris, M.K., Sotomayor-Gonz\u00e1lez, A., Glasner, D.R., Reyes, K.R., and Gliwa, A.S. (2021). Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. medRxiv.","DOI":"10.1016\/j.cell.2021.04.025"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2020.07.012","article-title":"The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity","volume":"182","author":"Li","year":"2020","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30494","DOI":"10.2807\/1560-7917.ES.2017.22.13.30494","article-title":"GISAID: Global initiative on sharing all influenza data\u2014From vision to reality","volume":"22","author":"Shu","year":"2017","journal-title":"Euro Surveill."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"W619","DOI":"10.1093\/nar\/gkab417","article-title":"The COVID-19 Data Portal: Accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing","volume":"49","author":"Harrison","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Colson, P., Levasseur, A., Delerce, J., Pinault, L., Dudouet, P., Devaux, C., Fournier, P.E., La Scola, B., Lagier, J.C., and Raoult, D. (2021). Spreading of a new SARS-CoV-2 N501Y spike variant in a new lineage. Clin. Microbiol. Infect.","DOI":"10.1016\/j.cmi.2021.05.006"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mallm, J.P., Bundschuh, C., Kim, H., Weidner, N., Steiger, S., Lander, I., B\u00f6rner, K., Bauer, K., H\u00fcbschmann, D., and Benes, V. (2021). Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein. medRxiv.","DOI":"10.1101\/2021.04.27.21254849"},{"key":"ref_13","unstructured":"Anoh, E.A., Schubert, G., Wayoro, O., Pac\u00f4me, M., Belarbi, E., Sachse, A., Calvignac-Spencer, S., Leendertz, F., Dian\u00e9, B., and Akoua-Koffi, C. (2021). SARS-CoV-2 variants of concern, variants of interest and lineage A.27 are on the rise in C\u00f4te d\u2019Ivoire. medRxiv."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Brandt, C., Krautwurst, S., Spott, R., Lohde, M., Jundzill, M., Marquet, M., and H\u00f6lzer, M. (2021). poreCov\u2014An easy to use, fast, and robust workflow for SARS-CoV-2 genome reconstruction via nanopore sequencing. Front. Genet.","DOI":"10.1101\/2021.05.07.443089"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1093\/bioinformatics\/bty407","article-title":"Nextstrain: Real-time tracking of pathogen evolution","volume":"34","author":"Hadfield","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"vex042","DOI":"10.1093\/ve\/vex042","article-title":"TreeTime: Maximum-likelihood phylodynamic analysis","volume":"4","author":"Sagulenko","year":"2018","journal-title":"Virus Evol."},{"key":"ref_19","first-page":"82","article-title":"PyMOL: An open-source molecular graphics tool","volume":"40","author":"DeLano","year":"2002","journal-title":"CCP4 Newsl. Protein Crystallogr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41594-020-00549-3","article-title":"A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent","volume":"28","author":"Xiao","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pirnay, J.P., Selhorst, P., Hong, S.L., Cochez, C., Potter, B., Maes, P., Petrillo, M., Dudas, G., Claes, V., and Van der Beken, Y. (2021). Variant Analysis of SARS-CoV-2 Genomes from Belgian Military Personnel Engaged in Overseas Missions and Operations. MDPI Viruses, 13.","DOI":"10.3390\/v13071359"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.3201\/eid1310.070253","article-title":"SurvNet electronic surveillance system for infectious disease outbreaks, Germany","volume":"13","author":"Krause","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Papa, G., Mallery, D.L., Albecka, A., Welch, L.G., Cattin-Ortol\u00e1, J., Luptak, J., Paul, D., McMahon, H.T., Goodfellow, I.G., and Carter, A. (2021). Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009246"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bestle, D., Heindl, M.R., Limburg, H., Van Lam van, T., Pilgram, O., Moulton, H., Stein, D.A., Hardes, K., Eickmann, M., and Dolnik, O. (2020). TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci. Alliance, 3.","DOI":"10.1101\/2020.04.15.042085"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.cell.2021.03.028","article-title":"N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2","volume":"184","author":"McCallum","year":"2021","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1056\/NEJMc2103740","article-title":"Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351","volume":"384","author":"Shen","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Motozono, C., Toyoda, M., Zahradnik, J., Ikeda, T., Saito, A., Tan, T.S., Ngare, I., Nasser, H., Kimura, I., and Uriu, K. (2021). An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity. BioRxiv.","DOI":"10.1101\/2021.04.02.438288"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.chom.2021.03.008","article-title":"SARS-CoV-2 spike variants exhibit differential infectivity and neutralization resistance to convalescent or post-vaccination sera","volume":"29","author":"Kuzmina","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","article-title":"mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants","volume":"592","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"De Oliveira, T., Lutucuta, S., Nkengasong, J., Morais, J., Paix\u00e3o, J.P., Neto, Z., Afonso, P., Miranda, J., David, K., and Ingl\u00eas, L. (2021). A novel variant of interest of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa. medRxiv.","DOI":"10.1101\/2021.03.30.21254323"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/s41467-021-21118-2","article-title":"SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity","volume":"12","author":"Ozono","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1038\/s41467-020-19808-4","article-title":"SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bugembe, D.L., V.T.Phan, M., Ssewanyana, I., Semanda, P., Nansumba, H., Dhaala, B., Nabadda, S., O\u2019Toole, \u00c1.N., Rambaut, A., and Kaleebu, P. (2021). A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic. MedRxiv.","DOI":"10.1101\/2021.02.08.21251393"},{"key":"ref_34","unstructured":"Mullen, J.L., Tsueng, G., Latif, A.A., Alkuzweny, M., Cano, M., Haag, E., Zhou, J., Zeller, M., Matteson, N., and Andersen, K.G. (2021, June 23). SARS-CoV-2 Lineage Comparison from outbreak.info. Available online: https:\/\/outbreak.info\/compare-lineages."},{"key":"ref_35","unstructured":"Mullen, J.L., Tsueng, G., Latif, A.A., Alkuzweny, M., Cano, M., Haag, E., Zhou, J., Zeller, M., Matteson, N., and Andersen, K.G. (2021, April 25). A.27 Lineage Report from outbreak.info. Available online: https:\/\/outbreak.info\/situation-reports?pango=A.27."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:55Z","timestamp":1760164615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081491"],"URL":"https:\/\/doi.org\/10.3390\/v13081491","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}