Background Access to molecular diagnosis was limited out-of-hospital in France during the 2020 coronavirus disease 2019 (COVID-19) epidemic. This study describes the evolution of COVID-19 outbreak in a nursing home in absence of molecular diagnosis. Methods A monocentric prospective study was conducted in a French nursing home from March 17th, 2020 to June 11th, 2020. Because of lack of molecular tests for severe acute respiratory syndrome 2 (SARS-Cov2) infection, probable COVID-19 cases were early identified considering only respiratory and not-respiratory symptoms and therefore preventing measures and treatments were enforced. Once available, serology tests were performed at the end of the study.A chronologic description of new cases and deaths was made together with a description of COVID-19 symptoms. Data about personal characteristics and treatments were collected and the following comparisons were performed: i) probable COVID-19 cases vs asymptomatic residents; ii) SARS-Cov2 seropositive residents vs seronegative residents. Results Overall, 32/66 (48.5%) residents and 19/39 (48.7%) members of health-care personnel were classified as probable COVID-19 cases. A total of 34/61 (55.7%) tested residents resulted seropositive. Death occurred in 4/66 (6%) residents. Diagnosis according to symptoms had 65% of sensitivity, 78% of specificity, 79% of positive predictive value and 64% of negative predictive value.In resident population, the following symptoms were registered: 15/32 (46.8%) lymphopenia, 15/32 (46.8%) fever, 8/32 (25%) fatigue, 8/32 (25%) cough, 6/32 (18.8%) diarrhoea, 4/32 (12.5%) severe respiratory distress requiring oxygen therapy, 4/32 (12.5%) fall, 3/32 (9.4%) conjunctivitis, 2/32 (6.3%) abnormal pulmonary noise at chest examination and 2/32 (6,25%) abdominal pain. Probable COVID-19 cases were older (81.3 vs 74.9; p=0.007) and they had higher prevalence of atrial fibrillation (8/32, 25% vs 2/34, 12%; p=0.030); insulin treatment (4/34, 12% vs 0, 0%; p=0.033) and positive SARS-Cov2 serology (22/32, 69% vs 12/34, 35%; p=0.001) than asymptomatic residents. Seropositive residents had lower prevalence of diabetes (4/34, 12% vs 9/27, 33%; p=0.041) and angiotensin-converting-enzyme inhibitors’ intake (1/34, 1% vs 5/27, 19%; p=0.042). Conclusions During SARS-Cov2 epidemic, early detection of respiratory and not-respiratory symptoms allowed to enforce extraordinary measures. They achieved limiting contagion and deaths among nursing home residents, even in absence of molecular diagnosis.