The coronavirus disease 2019 (COVID-19) pandemic poses special challenges to immunocompromised transplant patients. Given the paucity of proven data in treating COVID-19, management of these patients is difficult, rapidly evolving, and mainly based on anecdotal experience. We report 2 cases of heart transplant (HT) recipients with COVID-19. The first is a 59-year-old female with HT in 2012 who presented on March 20, 2020 with fever, hypoxia, and ground-glass opacities on chest X-ray. She quickly progressed to acute hypoxic respiratory failure and vasoplegic shock. Despite reduction in immunosuppression and treatment with tocilizumab, intravenous immunoglobulin, hydroxychloroquine, lopinavir/ritonavir, and broad-spectrum antibiotics, she ultimately died from multiorgan failure. The second case is a 75-year-old man with HT in 2000 who presented on April 2, 2020 after curbside testing revealed positive COVID-19. Given a milder presentation compared to the first patient, antimetabolite was discontinued and only hydroxychloroquine was started. Because of a lack of clinical improvement several days later, tocilizumab, methylprednisolone, and therapeutic anticoagulation were initiated. The patient clinically improved with decreasing oxygen requirements and was discharged home. These 2 cases highlight the wide range of different presentations of COVID-19 in HT recipients and the rapidity with which the management of these patients is evolving.

Induction therapy is the use of potent immunosuppression in the perioperative period with the intent to diminish rejection rates in at-risk patients or as a renal-protective strategy. The potent immunomodulatory effects of these agents must be balanced against the recipient’s risk of infectious or malignant complications, among others. There is a notable lack of clinically useful risk stratification models that integrate these competing risks and guide the clinician in the use of these therapies. This review integrates the existing evidence on the utility and safety of various induction regimens and highlights the gaps of knowledge in the field. In addition, we frame the discussion in view of the changing landscape of heart transplantation where many unknowns remain, such as the impact of induction immunosuppression on patients bridged with mechanical circulatory devices or receiving organs from hepatitis C–positive or donation after circulatory death donors, among others.