Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series.
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Böhmer Merle M, Buchholz Udo, Corman Victor M, Hoch Martin, Katz Katharina, Marosevic Durdica V, Böhm Stefanie, Woudenberg Tom, Ackermann Nikolaus, Konrad Regina, Eberle Ute, Treis Bianca, Dangel Alexandra, Bengs Katja, Fingerle Volker, Berger Anja, Hörmansdorfer Stefan, Ippisch Siegfried, Wicklein Bernd, Grahl Andreas, Pörtner Kirsten, Muller Nadine, Zeitlmann Nadine, Boender T Sonia, Cai Wei, Reich Andreas, An der Heiden Maria, Rexroth Ute, Hamouda Osamah, Schneider Julia, Veith Talitha, Mühlemann Barbara, Wölfel Roman, Antwerpen Markus, Walter Mathias, Protzer Ulrike, Liebl Bernhard, Haas Walter, Sing Andreas, Drosten Christian, Zapf Andreas
Аннотация
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.