Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series

Merle M Böhmer, Udo Buchholz, Victor M Corman, Martin Hoch, Katharina Katz, Durdica V Marosevic, Stefanie Böhm, Tom Woudenberg, Nikolaus Ackermann, Regina Konrad, Ute Eberle, Bianca Treis, Alexandra Dangel, Katja Bengs, Volker Fingerle, Anja Berger, Stefan Hörmansdorfer, Siegfried Ippisch, Bernd Wicklein, Andreas GrahlKirsten Pörtner, Nadine Muller, Nadine Zeitlmann, T Sonia Boender, Wei Cai, Andreas Reich, Maria An der Heiden, Ute Rexroth, Osamah Hamouda, Julia Schneider, Talitha Veith, Barbara Mühlemann, Roman Wölfel, Markus Antwerpen, Mathias Walter, Ulrike Protzer, Bernhard Liebl, Walter Haas, Andreas Sing, Christian Drosten, Andreas Zapf

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

BACKGROUND: In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates.

METHODS: A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs.

FINDINGS: Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3-4·3) and the median serial interval was 4·0 days (3·0-5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0-99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2-32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6-8·9; 11 of 217) among non-household, high-risk contacts.

INTERPRETATION: Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve.

FUNDING: All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Original languageEnglish
Pages (from-to)920-928
Number of pages9
JournalThe Lancet Infectious Diseases
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2020

Bibliographical note

Copyright © 2020 Elsevier Ltd. All rights reserved.

Funding

We thank all participants for sharing information necessary for the outbreak investigation and management. Moreover, we thank the company affected by the outbreak for a very good collaboration and great support with implementing the public health measures. We thank all county health authorities involved in the outbreak management as well as the Spanish health authorities for managing patient 12 and their contacts. Thanks also to Marie Reupke, Jörg Lekschas, and Joachim-Martin-Mehlitz (Robert Koch Institute) for their assistance in giving legal advice as well as Juliana Breitenberger, Linda Ploß, Christine Hartberger, Sabine Lohrer, Jasmin Fräßdorf, and Evelyn Bauermeister (Bavarian Health and Food Safety Authority) for expert technical assistance. Furthermore, we acknowledge the Cambridge High Performance Computing Service. Contributions by CD and VMC were funded by the German Ministry of Health (Konsiliarlabor für Coronaviren) and the German Center for Infection Research. SB, KP, and NM are fellows of the Postgraduate Training for Applied Epidemiology, supported financially by Robert Koch Institute. TW and TSB are fellows of the European Centre for Disease Prevention and Control (ECDC) Fellowship Programme, supported financially by the ECDC. The views and opinions expressed herein do not state or reflect those of ECDC. ECDC is not responsible for the data and information collation and analysis and cannot be held liable for conclusions or opinions drawn. We thank all participants for sharing information necessary for the outbreak investigation and management. Moreover, we thank the company affected by the outbreak for a very good collaboration and great support with implementing the public health measures. We thank all county health authorities involved in the outbreak management as well as the Spanish health authorities for managing patient 12 and their contacts. Thanks also to Marie Reupke, J?rg Lekschas, and Joachim-Martin-Mehlitz (Robert Koch Institute) for their assistance in giving legal advice as well as Juliana Breitenberger, Linda Plo?, Christine Hartberger, Sabine Lohrer, Jasmin Fr??dorf, and Evelyn Bauermeister (Bavarian Health and Food Safety Authority) for expert technical assistance. Furthermore, we acknowledge the Cambridge High Performance Computing Service. Contributions by CD and VMC were funded by the German Ministry of Health (Konsiliarlabor f?r Coronaviren) and the German Center for Infection Research. SB, KP, and NM are fellows of the Postgraduate Training for Applied Epidemiology, supported financially by Robert Koch Institute. TW and TSB are fellows of the European Centre for Disease Prevention and Control (ECDC) Fellowship Programme, supported financially by the ECDC. The views and opinions expressed herein do not state or reflect those of ECDC. ECDC is not responsible for the data and information collation and analysis and cannot be held liable for conclusions or opinions drawn.

FundersFunder number
German Ministry of Health
Konsiliarlabor für Coronaviren
Robert Koch Institute
Deutsches Zentrum für Infektionsforschung
European Centre for Disease Prevention and Control

    Keywords

    • Adolescent
    • Adult
    • Betacoronavirus/classification
    • COVID-19
    • Child
    • Child, Preschool
    • China
    • Communicable Diseases, Imported/epidemiology
    • Coronavirus Infections/epidemiology
    • Disease Outbreaks
    • Disease Transmission, Infectious
    • Germany/epidemiology
    • Humans
    • Interviews as Topic
    • Middle Aged
    • Mutation
    • Pandemics
    • Pneumonia, Viral/epidemiology
    • RNA, Viral/genetics
    • Reverse Transcriptase Polymerase Chain Reaction
    • Risk Assessment
    • SARS-CoV-2
    • Travel
    • Travel-Related Illness
    • Young Adult

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