Lessons from Two Early COVID-19 Hospital Outbreaks in Germany to Inform Strategies for Controlling Emerging Nosocomial Outbreaks of Highly Transmissible Respiratory Viruses

<b>Background/Objectives</b>: Nosocomial outbreaks of viral respiratory infections strain healthcare systems and endanger patients and healthcare workers (HCWs). We describe two large nosocomial outbreaks with the SARS-CoV-2 Alpha variant, during its initial emergence in Germany, to assess transmission dynamics, effectiveness of control measures, and challenges in managing highly transmissible respiratory viruses. <b>Methods</b>: Confirmed cases were inpatients, HCWs, or their contacts testing SARS-CoV-2-positive since 1 January 2021 (Hospital A [HA])) or 21 January 2021 (Hospital B [HB])) with N501Y and delH69/V70 spike gene mutations. We conducted case interviews, reviewed medical records and shift schedules, and performed sequencing, genome reconstruction, and phylogenetic analysis. We describe cases, transmission chains, and control measures. <b>Results</b>: HA reported 18 patient cases, 20 HCW cases, and 33 community cases (N = 71). HB reported 48 patient cases, 43 HCW cases (13 in a COVID-19 ward), and 27 community cases (N = 118). In-hospital transmission occurred patient-to-patient, HCW-to-patient, patient-to-HCW, and HCW-to-HCW. HA halted admissions immediately after the initial cases; HB implemented measures gradually. Regular testing detected pre-symptomatic (HA = 6; HB = 18) and asymptomatic cases (HA = 3; HB = 13). Testing of agency staff was incomplete. The suspected primary case was an HCW in HA and a patient in HB who required resuscitation shortly after admission. <b>Conclusions</b>: Early COVID-19 outbreaks offer valuable lessons for managing emerging nosocomial outbreaks of highly transmissible respiratory viruses. Our findings provide empirical evidence for effective interventions, including rapid response, testing, HCW protection, and rigorous contact tracing in high-risk emergency situations. Managing agency staff remains a major challenge.