Background Access to molecular diagnosis was limited out-of-hospital in France during the 2020 coronavirus disease MESHD 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 MESHD 2 (SARS-Cov2) infection MESHD, 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 MESHD 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 TRANS 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 MESHD occurred in 4/66 (6%) residents. Diagnosis according to symptoms had 65% of sensitivity SERO, 78% of specificity, 79% of positive predictive value SERO and 64% of negative predictive value SERO.In resident population, the following symptoms were registered: 15/32 (46.8%) lymphopenia MESHD lymphopenia HP, 15/32 (46.8%) fever MESHD fever HP, 8/32 (25%) fatigue MESHD fatigue HP, 8/32 (25%) cough MESHD cough HP, 6/32 (18.8%) diarrhoea, 4/32 (12.5%) severe respiratory distress HP requiring oxygen therapy, 4/32 (12.5%) fall HP, 3/32 (9.4%) conjunctivitis MESHD conjunctivitis HP, 2/32 (6.3%) abnormal pulmonary noise at chest examination and 2/32 (6,25%) abdominal pain MESHD abdominal pain HP. Probable COVID-19 cases were older (81.3 vs 74.9; p=0.007) and they had higher prevalence SERO of atrial fibrillation MESHD atrial fibrillation HP (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 TRANS residents. Seropositive residents had lower prevalence SERO 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 MESHD among nursing home residents, even in absence of molecular diagnosis.