Monkeypox virus is an emergent human pathogen. While it is less lethal than smallpox, it can still cause significant morbidity and mortality. In this review, we explore three antiviral agents with activity against monkeypox and other orthopoxviruses: cidofovir, brincidofovir, and tecovirimat. Cidofovir, and its prodrug brincidofovir, are inhibitors of DNA replication with a broad spectrum of activity against multiple families of double-stranded DNA viruses. Tecovirimat has more specific activity against orthopoxviruses, and inhibits the formation of the extracellular enveloped virus necessary for cell-to-cell transmission. For each agent, we review basic pharmacology, data from animal models and reported experience in human patients.

Background Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections. Methods This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for during March 2016 to October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis. Results Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT, and 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26, 95% CI 0.16-0.41), CMV end-organ disease (HR 0.23, 95% CI 0.10-0.52), refractory or resistant CMV infection (HR 0.15, 95% CI 0.04-0.52), and non-relapse mortality at week 48 (HR 0.55, 95% CI 0.32-0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group. Conclusions Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases non-relapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.

Coronavirus disease 2019 , secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic, presenting unprecedented challenges to health-care providers and systems. 1 The immunopathogenesis of COVID-19 is intriguing as it involves virus-driven tissue damage intertwined with an uncontrolled inflammatory response, contributing to severity of disease, acute respiratory distress syndrome (ARDS), and multiple organ failure. 2 Hematopoietic cell transplant (HCT) recipients are severely immunocompromised, with increased risk of severe COVID-19 secondary to the myeloablative conditioning regimens, organ damage, and possible immune recovery leading to an exuberant inflammatory reaction. A comprehensive approach to manage HCT recipients with COVID-19 at different stages after HCT (pre-engraftment, early and late post-engraftment) is lacking in terms of the potential role of early or pre-emptive antiviral use and/or immunomodulators that may improve clinical outcomes. In this brief report, we present two patients with COVID-19 pneumonia that occurred during the pre-engraftment period after HCT at our comprehensive cancer center. Additionally, we review the previously reported cases of COVID-19 in adults HCT recipients until December 31st, 2020, for whom sufficient data were available. [3][4][5][6][7][8][9][10][11][12][13]

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