This case report describes a 45-year-old man with severe antiphospholipid syndrome and diffuse alveolar hemorrhage who was immunocompromised and receiving multiple medications. He was hospitalized with fever and diagnosed with Covid-19, receiving remdesivir and increasing glucocorticoid doses. Despite initial improvement, he experienced multiple hospitalizations for abdominal pain, fatigue, and dyspnea, leading to concerns about recurrent diffuse alveolar hemorrhage. The patient's SARS-CoV-2 infection recurred multiple times, with RT-PCR Ct values fluctuating between 27.6 and 15.6, requiring multiple courses of remdesivir and other treatments. Phylogenetic analysis revealed persistent infection and accelerated viral evolution, particularly in the spike gene and receptor-binding domain. The patient ultimately died from shock and respiratory failure. This case highlights the potential for persistent SARS-CoV-2 infection and accelerated viral evolution in immunocompromised individuals.This case report describes a 45-year-old man with severe antiphospholipid syndrome and diffuse alveolar hemorrhage who was immunocompromised and receiving multiple medications. He was hospitalized with fever and diagnosed with Covid-19, receiving remdesivir and increasing glucocorticoid doses. Despite initial improvement, he experienced multiple hospitalizations for abdominal pain, fatigue, and dyspnea, leading to concerns about recurrent diffuse alveolar hemorrhage. The patient's SARS-CoV-2 infection recurred multiple times, with RT-PCR Ct values fluctuating between 27.6 and 15.6, requiring multiple courses of remdesivir and other treatments. Phylogenetic analysis revealed persistent infection and accelerated viral evolution, particularly in the spike gene and receptor-binding domain. The patient ultimately died from shock and respiratory failure. This case highlights the potential for persistent SARS-CoV-2 infection and accelerated viral evolution in immunocompromised individuals.