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Objective: To assess the American Testing Guidance for Nursing Homes (NHs)-updated May 19, 2020-with a new COVID-19 case.Design: Case investigation.Setting and subjects: All 79 residents and 34 health care personnel (HCP) of an NH.Methods: Seven days after identification of a COVID-19 resident, all residents and HCP underwent real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for SARS-CoV-2 with nasopharyngeal swabs. This was repeated weekly in all previously negative subjects until the testing identified no new cases, and in all positive subjects until the testing was negative. COVID-19 infection prevention and control (IPC) measures were implemented in all residents and HCP with positive testing or with COVID-19 symptoms. Standard IPC was also implemented in all HCP. Six weeks after initial testing, all residents underwent testing for enzyme-linked immunosorbent assay-based IgG antibodies directed against the SARS-CoV-2. Symptoms were serially recorded in residents and HCP.Results: A total of 36 residents had a positive rRT-PCR at baseline and 2 at day 7. Six HCP had a positive rRT-PCR at baseline and 2 at day 7. No new COVID-19 cases were diagnosed later. Among the SARS-CoV-2-positive cases, 6 residents (16%) and 3 HCP (37%) were asymptomatic during the 14 days before testing. Twenty-five residents (92.3%) and all 8 HCP (100%) with a positive rRT-PCR developed IgG antibodies against SARS-CoV-2. Among the residents and HCP always having tested negative, 2 (5%) and 5 (11.5%), respectively, developed IgG antibodies against SARS-CoV-2. These 2 residents had typical COVID-19 symptoms before and after testing and 2/5 HCP were asymptomatic before and after testing.Conclusions and implications: This study shows the validity of the updated American Testing Guidance for Nursing Homes (NHs). It suggests implementing COVID-19 IPC in both residents and HCP with positive testing or COVID-19 symptoms and warns that asymptomatic HCP with repeated negative rRT-PCR testing can develop antibodies against SARS-CoV-2.