Received  her first COVID vaccine on Thursday, March 18.  On 3/23/21 she started to have new onset of generalized muscles aches and weakness.  She started feeling some pain in her back, which then spread to arms and legs. She is now beginning to feel weakness in her core and extremities. Having difficulty lifting arms above head. She is still able to walk without difficulty but legs do feel weak. Increase in SOB as well. Myalgias and chest pain resolved within a week, however she continued to feel weak, tired, and had DOE. She developed "brain fog" and talked to her boss about taking short-term disability as it had been hard to work.  No appetite. On 4/1/21, she presented to the ED with 2 weeks of worsening generalized weakness, SOB, lightheadedness, dizziness and found to have acute anemia. Was admitted for further workup.  Hgb at admission was 5.4.   This admission diagnosed her with a new warm autoantibody hemolytic anemia. This is new since the COVID vaccine was administered.  Upon admission there was no thrombocytopenia, so there was low suspicion for microangiopathic hemolytic anemia, TTP/HUS, or DIC. Peripheral blood smear at that time suggested a leukoerythroblastic blood picture (could be Bone Marrow recovery post chemo) but with marked normocytic, normochromic anemia, and with increased circulating erythroid precursors and increased red blood cell regeneration; spherocytes and fragments are present supporting hemolysis.  DAT positive (both IgG and C3) along with other hemolysis lab including elevated LDH, Bilirubin, haptoglobin 3, and PBS c/w hemolysis; no evidence of MAHA. So warm autoantibody hemolytic anemia is the most likely explanation. She had negative cold agglutinin antibodies <1:32 on 4/9. Started on methylprednisolone on 4/2/21, but Hgb continued to steadily decline despite treatment. Continued on methylprednisolone 87.5mg daily. Rituxan 375mg/m2 was started on 4/6/21 with plans for weekly infusions for a total of 4 weeks.  there was concern for a GI bleed on 4/10-4/11 due to bright red fluid appearing like blood in the toilet after a stool. This led to her receiving roughly 5 units of pRBCs. After these 5 units she started urinating red urine and we became highly concerned for hyperhemolysis. She did not have any further stools so we did not think a GI bleed was likely.    She was given 1 dose of Eculizumab (Soliris) (4/12). This treatment is for complement mediated intravascular hyperhemolysis. Unfortunately it did not appear to help her.   On 4/14, we were thinking TTP could be contributory with numerous schistocytes on peripheral smear. Her T bili was up to 7.8, and her hemoglobin plasma was trending up, in the 380 -- > 610 and in the 800s today. Cr was worsening. Platelet count was dropping.  With her worsening condition and concern for both hyperhemolysis and possible TTP, we decided to start her plasma exchange followed by her second dose of Rituximab.  Unfortunately she became disoriented/confused following line placement and while receiving plasmaphoresis. CT head returned without acute findings. She then had an allergic reaction with a rash during PLEX which was stopped (4L completed with a goal of 5L). Improved with benadryl.  She was then administered rituximab. Then she developed worsening sinus tachycardia and HTN.   Her respiratory status deteriorated and she eventually required high-flow oxygen to maintain saturations > 90%. CXR showed bilateral opacities, not drastically changed from previous films. Rituximab was stopped halfway through its infusion in case this was an adverse effect to the drug. She was given 20 mg IV Lasix per the nighttime sign-out. She was initially given ceftriaxone and azithromycin IV to cover CAP but later ABx were broadened to vanc and Zosyn with rising lactate of unknown source.   Ultimately she had acute respiratory failure with hypoxia and need BiPAP. She was eventually intubated and a code blue was called.  She unfortunately died shortly after intubation.