ABSTRACT Background: Hemoglobin D – Los Angeles (HbD) is a variant hemoglobin that can polymerize in the deoxygenated state. When co-inherited with Hemoglobin S (HbSD disease) a severe sickling syndrome can result. Infection with SARS-CoV-2 has been associated with acute chest syndrome (ACS) in individuals with sickle cell disease (SCD), but this complication has not previously been reported in patients with HbSD. Dexamethasone has been shown to improve outcomes in non-sickle cell patients with SARS-CoV-2 pneumonia or adult respiratory distress syndrome (ARDS); however, its use in SCD patients with ACS is controversial due to a reported increased risk of complications including vaso-occlusive painful episodes (VOE). Procedure: Case Report and literature review focusing on the management of pediatric SCD patients with SARS-CoV-2 associated ACS. Results: A 7-year-old female with HbSD presented with fever, cough, shortness of breath, hypoxia and pulmonary infiltrates consistent with ACS. She tested positive for SARS-CoV-2. She began treatment with dexamethasone (6 mg/ kg/ day divided BID). She had a rapid recovery without sequalae from steroid use. Literature review identified 39 pediatric patients with SCD and COVID-19, of whom 21 (54%) had ACS. Simple transfusion (9 pts) and exchange transfusion (3 pts) were the most frequently reported treatment, with hydroxychloroquine (5 pts), remdesivir (1pt), and tocilizumab (1 pt) also being reported. Three patients were treated with dexamethasone. All 3 recovered and no adverse outcomes from steroid use were reported. Conclusions: Further study is needed to determine the optimal treatment of SARS-CoV-2 associated ACS; however, dexamethasone should be considered.