This report details a significant increase in Kaposi Sarcoma–Associated Herpesvirus (KSHV) infections and complications among solid organ transplant recipients in the United States between January 2021 and September 2025. Forty-six deceased donors were suspected of transmitting KSHV, leading to 74 (48%) of 153 recipients developing post-transplantation KSHV infection. Clinical presentations included Kaposi sarcoma (61%), lymphoproliferative disorders (14%), and KSHV inflammatory cytokine syndrome (8%), with 25 (16%) recipient deaths. Most donors and recipients were HIV-negative, but two-thirds of donors had a history of nonmedical drug use, indicating a changing risk profile for KSHV transmission. Diagnosis relied on molecular, serologic, or immunohistochemical assays.
Key note: Clinicians must maintain a high index of suspicion for KSHV in transplant recipients, especially with donor risk factors like nonmedical drug use, to facilitate prompt diagnosis and management.