In organ-transplant recipients, the standard two-dose vaccination strategy for coronavirus disease 2019 (Covid-19) has suboptimal immunogenicity.¹ Both patients and health care providers have questioned whether a third-dose booster in transplant recipients would be safe and enhance immune response.² We performed a double-blind, randomized, controlled trial of a third dose of mRNA-1273 vaccine (Moderna) as compared with placebo (the protocol is available with the full text of this letter at NEJM.org; ClinicalTrials.gov number, NCT04885907).

The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases and the influence of transplant societies for education and disseminating current information.

The annual standard dose influenza vaccine has suboptimal immunogenicity in solid organ transplant recipients (SOTR). Influenza vaccine containing higher doses of antigens may lead to greater immunogenicity in this population. We conducted a randomized, double blind trial comparing the safety and immunogenicity of the 2016-17 high dose (HD; FluzoneHD,Sanofi) versus standard dose (SD; Fluviral,GSK) influenza vaccine in adult SOTR. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay. We enrolled 172 patients who received study vaccine and 161 (84 HD; 77 SD) were eligible for analysis. Seroconversion to at least 1 of 3 vaccine antigens was present in 78.6% vs. 55.8% in HD vs. SD vaccine respectively (p<0.001). Seroconversion to A/ H1N1, A/H3N2 and B strains were 40.5% vs. 20.5%, 57.1% vs. 32.5%, and 58.3% vs. 41.6% in HD vs. SD vaccine (p=0.006, 0.002, 0.028 respectively). Post-immunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in HD group (p=0.007, 0.002, 0.033). Independent factors associated with seroconversion to at least one vaccine strain were the use of HD vaccine (OR 3.23, 95% CI 1.56-6.67) and use of mycophenolate doses less than 2g daily (OR 2.76, 95% CI 1.12-6.76). High-dose vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population.

Seasonal influenza infection may cause significant morbidity and mortality in transplant recipients. The purpose of this study was to assess the epidemiology of symptomatic influenza infection posttransplant and determine risk factors for severe disease. Twenty centers in the United States, Canada, and Spain prospectively enrolled solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) recipients with microbiologically confirmed influenza over 5 consecutive years (2010–2015). Demographics, microbiology data, and outcomes were collected. Serial nasopharyngeal swabs were collected at diagnosis and upto 28 days, and quantitative polymerase chain reaction for influenza A was performed. We enrolled 616 patients with confirmed influenza (477 SOT; 139 HSCT). Pneumonia at presentation was in 134 of 606 (22.1%) patients. Antiviral therapy was given to 94.1% for a median of 5 days (range, 1–42 days); 66.5% patients were hospitalized and 11.0% required intensive care unit (ICU) care. The receipt of vaccine in the same influenza season was associated with a decrease in disease severity as determined by the presence of pneumonia (odds ratio [OR], 0.34 [95% confidence interval {CI}, .21–.55], P < .001) and ICU admission (OR, 0.49 [95% CI, .26–.90], P = .023). Similarly, early antiviral treatment (within 48 hours) was associated with improved outcomes. In patients with influenza A, pneumonia, ICU admission, and not being immunized were also associated with higher viral loads at presentation (P = .018, P = .008, and P = .024, respectively). Annual influenza vaccination and early antiviral therapy are associated with a significant reduction in influenza-associated morbidity, and should be emphasized as strategies to improve outcomes of transplant recipients.

Cell‐mediated immune responses predict clinical cytomegalovirus (CMV) events but have not been adopted into routine practice due to lack of interventional studies. Our objective was to demonstrate the safety and feasibility of early discontinuation of antivirals based on the real‐time measurement of CMV‐specific cell‐mediated immunity (CMI) in patients with CMV viremia. Transplant patients were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T cell responses were determined using the Quantiferon‐CMV assay, and results were used to guide subsequent management. A total of 27 patients (median viral load at onset 10 900 International Units/mL) were treated until viral load negative. At end of treatment, 14/27 (51.9%) had a positive CMV‐CMI response and had antivirals discontinued. The remaining 13/27 (48.1%) patients had a negative CMV‐CMI response and received 2 months of secondary antiviral prophylaxis. In those with a positive CMI and early discontinuation of antivirals, only a single patient experienced a low‐level asymptomatic recurrence. In contrast, recurrence was observed in 69.2% of CMI‐negative patients despite more prolonged antivirals (p = 0.001). In conclusion, this is the first study to demonstrate the feasibility and safety of real‐time CMV‐specific CMI assessment to guide changes to the management of CMV infection.