COVID-19 is a global pandemic that we fight all over the world. Its molecular structure aim for its atypical manifestations & different immune response in individuals. We report a case of Down syndrome with COVID-19 infection ended by death, unfortunately. A young female patient aged 15 y with Down syndrome complained of dry cough, fever & chest pain since 1 week not relieved by course of antibiotics in outpatient clinic. She presented in tertiary care hospital by dyspnea at rest & cyanosis for endotracheal intubation. Laboratory findings revealed low oxygen saturation, lymphopenia & anemia. By the way she is cardiac & had ASD & VSD since birth. The nasopharyngeal swab was positive for corona virus. Plain x-ray chest & NCCT scan of the chest were done & they are non-specific & lead us to a big dilemma, that's why multi-specialty consultants were contributed to preserve her life, but they failed.