Patients with SCD often have underlying cardiopulmonary co-morbidities that may predispose them to poor outcomes if they become infected with SARS-CoV-2. A large study of electronic health record data identified 312 patients with COVID-19 and SCD between January 20, 2020, to September 20, 2020.1 After propensity score matching, patients with COVID-19 and SCD remained at a higher risk of hospitalization (relative risk [RR], 2.0; 95% CI, 1.5-2.7), development of pneumonia (RR, 2.4; 95% CI, 1.6-3.4), and pain (RR, 3.4; 95% CI, 2.5-4.8) compared with Black individuals without SCD. Case fatality rates for SCD patients were not significantly different from those of Black individuals without SCD. A smaller study from four major metropolitan cities in the United States identified indivduals with SCD with the following risk factors for higher incidence of death from COVID-19: pre-existing cardiopulmonary illness, renal disease, and/or stroke; not receiving hydroxyurea; presenting with high serum creatinine, lactate dehydrogenase, and/or D-dimer levels.2 SCD patients infected with SARS-CoV-2 should be followed very closely, applying a low threshold for admission and frequent outpatient check-ins via telemedicine or in person as appropriate, particularly following hospital discharge. The Sickle Cell Disease Association of America updates its recommendations frequently about best practices for the care of SCD patients in the era of COVID-19. Below, we address FAQs that arise most commonly from providers less familiar with SCD. How should I evaluate respiratory symptoms in children and adults with an active COVID-19 infection? There is significant overlap in presenting symptoms between COVID-19, acute chest syndrome (ACS) and other infectious causes of pneumonia. Providers should test for COVID-19 and other infectious pathogens and have a low threshold for imaging. COVID-19 most commonly presents with a more diffuse ground glass appearance, versus more localized infiltrates consistent with consolidation. These findings are not always distinct, and all possibilities should remain in the differential. A detailed checklist for evaluating SCD patients with these symptoms in the emergency department has been developed by ASH in collaboration with ED physicians. Often transfusion therapy is the only effective intervention for respiratory failure due to ACS, with a goal to reduce the hemoglobin S (HbS) level to approximately 15% via exchange transfusion, in order to ensure that HbS levels remain less than 30% for approximately 4 weeks. Whether reducing HbS via transfusion improves outcome in COVID-19 respiratory failure is unknown, but decreased sickling in this setting as in ACS would seem desirable. Whether reduction of HbS to < 15% should be pursued will be based on the patient's clinical acuity, availability of appropriate red blood cell units, and feasibility of RBC exchange apheresis at the local facility. Fllowing automated exchange transfusion, a hemoglobin between 10 and 12g/dL should be targeted to maximize oxygen carrying capacity.