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In the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data.


We applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata.


We investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission.


We identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions.


Early spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.


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  1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.  https://doi.org/10.1038/s41586-020-2012-7  PMID: 32015507 
  2. Fauver JR, Petrone ME, Hodcroft EB, Shioda K, Ehrlich HY, Watts AG, et al. Coast-to-coast spread of SARS-CoV-2 during the early epidemic in the United States. Cell. 2020;181(5):990-6.e5.  https://doi.org/10.1016/j.cell.2020.04.021 
  3. Lemieux J, Siddle KJ, Shaw BM, Loreth C, Schaffner S, Gladden-Young A, et al. Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events. medRxiv. 2020.08.23.20178236. Preprint. https://doi.org/10.1101/2020.08.23.20178236
  4. Deng X, Gu W, Federman S, du Plessis L, Pybus OG, Faria NR, et al. Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California. Science. 2020;369(6503):582-7.  https://doi.org/10.1126/science.abb9263  PMID: 32513865 
  5. Gonzalez-Reiche AS, Hernandez MM, Sullivan MJ, Ciferri B, Alshammary H, Obla A, et al. Introductions and early spread of SARS-CoV-2 in the New York City area. Science. 2020;369(6501):297-301.  https://doi.org/10.1126/science.abc1917  PMID: 32471856 
  6. Miller D, Martin M, Harel N, Kustin T, Tirosh O, Meir M, et al. Full genome viral sequences inform patterns of SARS-CoV-2 spread into and within Israel. medRxiv; 2020.05.21.20104521. Preprint. https://doi.org/10.1101/2020.05.21.20104521
  7. European Centre for Disease Prevention and Control (ECDC). COVID-19 situation dashboard. Stockholm: ECDC. [Accessed: 20 Oct 2020]. Available from: https://qap.ecdc.europa.eu/public/extensions/COVID-19/COVID-19.html#global-overview-tab
  8. Alm E, Broberg EK, Connor T, Hodcroft EB, Komissarov AB, Maurer-Stroh S, et al. Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020. Euro Surveill. 2020;25(32):2001410.  https://doi.org/10.2807/1560-7917.ES.2020.25.32.2001410  PMID: 32794443 
  9. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data – from vision to reality. Euro Surveill. 2017;22(13):30494.  https://doi.org/10.2807/1560-7917.ES.2017.22.13.30494 
  10. Grubaugh ND, Ladner JT, Kraemer MUG, Dudas G, Tan AL, Gangavarapu K, et al. Genomic epidemiology reveals multiple introductions of Zika virus into the United States. Nature. 2017;546(7658):401-5.  https://doi.org/10.1038/nature22400  PMID: 28538723 
  11. Robert Koch Institute (RKI). Kontaktpersonen-Nachverfolgung bei respiratorischen Erkrankungen durch das Coronavirus SARS-CoV-2. [Contact tracing for respiratory infections caused by SARS-CoV-2]. Berlin: RKI; 2021. German. Available from: https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Kontaktperson/Management.html#doc13516162bodyText10
  12. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199-207.  https://doi.org/10.1056/NEJMoa2001316  PMID: 31995857 
  13. Muenchhoff M, Mairhofer H, Nitschko H, Grzimek-Koschewa N, Hoffmann D, Berger A, et al. Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020. Euro Surveill. 2020;25(24):2001057.  https://doi.org/10.2807/1560-7917.ES.2020.25.24.2001057  PMID: 32583765 
  14. Quick J. nCoV-2019 sequencing protocol v2 (GunIt) V.2. Berkeley: protocols.io; 2020 .Available from: https://www.protocols.io/view/ncov-2019-sequencing-protocol-v2-bdp7i5rn?version_warning=no
  15. Kreidl P, Schmid D, Maritschnik S, Richter L, Borena W, Genger JW, et al. Emergence of coronavirus disease 2019 (COVID-19) in Austria. Wien Klin Wochenschr. 2020;132(21-22):645-52.  https://doi.org/10.1007/s00508-020-01723-9  PMID: 32816114 
  16. Böhmer MM, Buchholz U, Corman VM, Hoch M, Katz K, Marosevic DV, et al. Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series. Lancet Infect Dis. 2020;20(8):920-8.  https://doi.org/10.1016/S1473-3099(20)30314-5  PMID: 32422201 
  17. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. 2020;382(10):970-1.  https://doi.org/10.1056/NEJMc2001468  PMID: 32003551 
  18. Wolf GK, Glueck T, Huebner J, Muenchhoff M, Hoffmann D, French LE, et al. Clinical and epidemiological features of a family cluster of symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2 infection. J Pediatric Infect Dis Soc. 2020;9(3):362-5.  https://doi.org/10.1093/jpids/piaa060  PMID: 32441753 
  19. Danis K, Epaulard O, Bénet T, Gaymard A, Campoy S, Botelho-Nevers E, et al. Cluster of coronavirus disease 2019 (COVID-19) in the French Alps, February 2020. Clin Infect Dis. 2020;71(15):825-32.  https://doi.org/10.1093/cid/ciaa424  PMID: 32277759 
  20. Popa A, Genger JW, Nicholson MD, Penz T, Schmid D, Aberle SW, et al. Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2. Sci Transl Med. 2020;12(573):eabe2555.  https://doi.org/10.1126/scitranslmed.abe2555  PMID: 33229462 
  21. Walker A, Houwaart T, Wienemann T, Vasconcelos MK, Strelow D, Senff T, et al. Genetic structure of SARS-CoV-2 reflects clonal superspreading and multiple independent introduction events, North-Rhine Westphalia, Germany, February and March 2020. Euro Surveill. 2020;25(22):2000746.  https://doi.org/10.2807/1560-7917.ES.2020.25.22.2000746  PMID: 32524946 
  22. Rhee C, Baker M, Vaidya V, Tucker R, Resnick A, Morris CA, et al. Incidence of nosocomial COVID-19 in patients hospitalized at a large US academic medical center. JAMA Netw Open. 2020;3(9):e2020498.  https://doi.org/10.1001/jamanetworkopen.2020.20498  PMID: 32902653 
  23. Rickman HM, Rampling T, Shaw K, Martinez-Garcia G, Hail L, Coen P, et al. Nosocomial transmission of COVID-19: a retrospective study of 66 hospital-acquired cases in a London teaching hospital. Clin Infect Dis. 2021;72(4):690-3.
  24. Schünemann HJ, Khabsa J, Solo K, Khamis AM, Brignardello-Petersen R, El-Harakeh A, et al. ventilation techniques and risk for transmission of coronavirus disease, including COVID-19: a living systematic review of multiple streams of evidence. Ann Intern Med. 2020;173(3):204-16.  https://doi.org/10.7326/M20-2306  PMID: 32442035 
  25. Harding H, Broom A, Broom J. Aerosol-generating procedures and infective risk to healthcare workers from SARS-CoV-2: the limits of the evidence. J Hosp Infect. 2020;105(4):717-25.  https://doi.org/10.1016/j.jhin.2020.05.037  PMID: 32497651 
  26. Harris SR, Cartwright EJ, Török ME, Holden MT, Brown NM, Ogilvy-Stuart AL, et al. Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis. 2013;13(2):130-6.  https://doi.org/10.1016/S1473-3099(12)70268-2  PMID: 23158674 
  27. Lucey M, Macori G, Mullane N, Sutton-Fitzpatrick U, Gonzalez G, Coughlan S, et al. Whole-genome sequencing to track severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in nosocomial outbreaks. Clin Infect Dis. 2020. PMID: 32954414 
  28. Tyson JR, James P, Stoddart D, Sparks N, Wickenhagen A, Hall G, et al. Improvements to the ARTIC multiplex PCR method for SARS-CoV-2 genome sequencing using nanopore. bioRxiv. 2020;2020.09.04.283077. Preprint. https://doi.org/10.1101/2020.09.04.283077 PMID:32908977
  29. Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G, Trebes A, et al. Shared SARS-CoV-2 diversity suggests localised transmission of minority variants. bioRxiv. 2020:2020.05.28.118992. Preprint. https://doi.org/10.1101/2020.05.28.118992
  30. Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G, Trebes A, et al. SARS-CoV-2 within-host diversity and transmission. Science. 2021;372(6539):eabg0821.  https://doi.org/10.1126/science.abg0821  PMID: 33688063 
  31. Villabona-Arenas CJ, Hanage WP, Tully DC. Phylogenetic interpretation during outbreaks requires caution. Nat Microbiol. 2020;5(7):876-7.  https://doi.org/10.1038/s41564-020-0738-5  PMID: 32427978 

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