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Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series.
Lancet Infect Dis. 2020 08; 20(8):920-928.LI

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.

Authors+Show Affiliations

Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; Institute of Social Medicine and Health Systems Research, Otto-von-Guericke-University, Magdeburg, Germany. Electronic address: merle.boehmer@lgl.bayern.de.Robert Koch Institute, Berlin, Germany.Institute of Virology, Charité University Medicine, Berlin, Germany; German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; Postgraduate Training for Applied Epidemiology, Berlin, Germany; ECDC Fellowship Programme, Field Epidemiology Path, European Centre for Disease Prevention and Control, Stockholm, Sweden.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; ECDC Fellowship Programme, Field Epidemiology Path, European Centre for Disease Prevention and Control, Stockholm, Sweden.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Postgraduate Training for Applied Epidemiology, Berlin, Germany; ECDC Fellowship Programme, Field Epidemiology Path, European Centre for Disease Prevention and Control, Stockholm, Sweden.Postgraduate Training for Applied Epidemiology, Berlin, Germany; ECDC Fellowship Programme, Field Epidemiology Path, European Centre for Disease Prevention and Control, Stockholm, Sweden.Robert Koch Institute, Berlin, Germany.Postgraduate Training for Applied Epidemiology, Berlin, Germany; ECDC Fellowship Programme, Field Epidemiology Path, European Centre for Disease Prevention and Control, Stockholm, Sweden.Robert Koch Institute, Berlin, Germany.Robert Koch Institute, Berlin, Germany.Robert Koch Institute, Berlin, Germany.Robert Koch Institute, Berlin, Germany.Robert Koch Institute, Berlin, Germany.Institute of Virology, Charité University Medicine, Berlin, Germany.Institute of Virology, Charité University Medicine, Berlin, Germany.Institute of Virology, Charité University Medicine, Berlin, Germany; German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany.German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany; Bundeswehr Institute of Microbiology, Munich, Germany.German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany; Bundeswehr Institute of Microbiology, Munich, Germany.German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany; Bundeswehr Institute of Microbiology, Munich, Germany.German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany; Institute of Virology, Technical University Munich, Munich, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; Ludwig-Maximilians University, Munich, Germany.Robert Koch Institute, Berlin, Germany.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany; Ludwig-Maximilians University, Munich, Germany.Institute of Virology, Charité University Medicine, Berlin, Germany; German Center for Infection Research, Partner Site Munich and Associated Partner Site Charité, Berlin, Germany. Electronic address: christian.drosten@charite.de.Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32422201

Citation

Böhmer, Merle M., et al. "Investigation of a COVID-19 Outbreak in Germany Resulting From a Single Travel-associated Primary Case: a Case Series." The Lancet. Infectious Diseases, vol. 20, no. 8, 2020, pp. 920-928.
Böhmer MM, Buchholz U, Corman VM, 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):920-928.
Böhmer, M. M., Buchholz, U., Corman, V. M., Hoch, M., Katz, K., Marosevic, D. V., Böhm, S., Woudenberg, T., Ackermann, N., Konrad, R., Eberle, U., Treis, B., Dangel, A., Bengs, K., Fingerle, V., Berger, A., Hörmansdorfer, S., Ippisch, S., Wicklein, B., ... Zapf, A. (2020). Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series. The Lancet. Infectious Diseases, 20(8), 920-928. https://doi.org/10.1016/S1473-3099(20)30314-5
Böhmer MM, 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):920-928. PubMed PMID: 32422201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series. AU - Böhmer,Merle M, AU - Buchholz,Udo, AU - Corman,Victor M, AU - Hoch,Martin, AU - Katz,Katharina, AU - Marosevic,Durdica V, AU - Böhm,Stefanie, AU - Woudenberg,Tom, AU - Ackermann,Nikolaus, AU - Konrad,Regina, AU - Eberle,Ute, AU - Treis,Bianca, AU - Dangel,Alexandra, AU - Bengs,Katja, AU - Fingerle,Volker, AU - Berger,Anja, AU - Hörmansdorfer,Stefan, AU - Ippisch,Siegfried, AU - Wicklein,Bernd, AU - Grahl,Andreas, AU - Pörtner,Kirsten, AU - Muller,Nadine, AU - Zeitlmann,Nadine, AU - Boender,T Sonia, AU - Cai,Wei, AU - Reich,Andreas, AU - An der Heiden,Maria, AU - Rexroth,Ute, AU - Hamouda,Osamah, AU - Schneider,Julia, AU - Veith,Talitha, AU - Mühlemann,Barbara, AU - Wölfel,Roman, AU - Antwerpen,Markus, AU - Walter,Mathias, AU - Protzer,Ulrike, AU - Liebl,Bernhard, AU - Haas,Walter, AU - Sing,Andreas, AU - Drosten,Christian, AU - Zapf,Andreas, Y1 - 2020/05/15/ PY - 2020/03/12/received PY - 2020/04/09/revised PY - 2020/04/09/accepted PY - 2020/5/19/pubmed PY - 2020/8/12/medline PY - 2020/5/19/entrez SP - 920 EP - 928 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 20 IS - 8 N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/32422201/Investigation_of_a_COVID_19_outbreak_in_Germany_resulting_from_a_single_travel_associated_primary_case:_a_case_series_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(20)30314-5 DB - PRIME DP - Unbound Medicine ER -