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Background Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19) and vaccine breakthrough infections are common. We determined the effectiveness of ≥3 doses of mRNA vaccine and early monoclonal antibody therapy in reducing disease severity against the Omicron (B.1.1.529) variant. Methods Prospective cohort study of consecutive SOT recipients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to our transplant center who were followed for at least 30 days. The primary outcome was supplemental oxygen requirement. Effectiveness of sotrovimab and ≥3 vaccine doses was estimated using adjusted risk ratios (RR). Results Three hundred adult organ transplant recipients were included. Seventy-one patients (24.1%) were hospitalized, 44 (14.9%) required supplemental oxygen, 19 (6.5%) were admitted to the intensive care unit (ICU), 15 (5.1%) required mechanical ventilation (MV), and 13 (4.4%) died. On multivariate analysis, age and multiple comorbidities were risk factors for oxygen requirement. Both receipt of ≥3 vaccine doses prior to SARS-CoV-2 infection and receipt of sotrovimab in the first 7 days of symptom onset was associated with a reduction in the need for supplemental oxygen (RR 0.30 [95% confidence interval {CI}:.17 to.54] and RR 0.24 (95% CI:.1 to.59), respectively]. For sotrovimab, the number needed to treat (NNT) to prevent one patient requiring oxygen was 6.64 (95% CI: 4.56–13.66). Both sotrovimab use and having received ≥3 vaccine doses were also associated with a shorter hospitalization length of stay. Conclusions In a cohort of SOT recipients with Omicron variant COVID-19 infection, prior receipt of ≥3 mRNA vaccine doses and early monoclonal antibody therapy were independently associated with significantly reduced disease severity. [ABSTRACT FROM AUTHOR]

Background: There are few interventional studies using CMV cell-mediated immunity (CMI) to guide antiviral prophylaxis. We assessed the Quantiferon-CMV (QTF-CMV) assay to guide CMV prophylaxis duration in high-risk organ transplant recipients., Methods: A single-arm, multicenter, prospective interventional study including high-risk kidney, pancreas, liver, and heart transplant recipients who were either donor CMV-seropositive, recipient-seronegative (D+/R-) or recipient-seropositive with antithymocyte globulin (R+/ATG) induction. CMI testing was performed using the QTF-CMV assay at months 3, 4, 5, and 6 posttransplant. Prophylaxis was discontinued for a positive CMI but continued for a negative result up to a maximum of 6 mo. The primary endpoint was CMV viremia ≥1000 IU/mL up to 1 y posttransplant., Results: One hundred eight patients were included, comprising kidney (n = 89), kidney-pancreas (n = 7), liver (n = 10), and heart (n = 2) transplants. Eighty-nine patients (82.4%) completed the study protocol (n = 39 D+/R- and n = 50 R+/ATG). In the D+/R- group, only 1 of 39 patients (2.6%) had a positive QTF-CMV result. In the R+/ATG group, 33 of 50 patients (66%) had a positive QTF-CMV result before 6 mo, allowing for early discontinuation of prophylaxis (28 at month 3, 4 at month 4, and 1 at month 5). During the follow-up, CMV viremia ≥1000 IU/mL occurred in only 4 of 33 patients (12.1%) who discontinued prophylaxis early compared with 6 of 17 patients (35.3%) with negative QTF-CMV results and continued prophylaxis (hazard ratio 0.31; 95% confidence interval, 0.09-1.09; P = 0.07). No R+ patient developed CMV disease., Conclusions: QTF-CMV-guided prophylaxis appears useful in R+ patients who may benefit from a tailored duration of prophylaxis. This strategy does not appear to be useful in D+/R- patients., Competing Interests: D.K. has received clinical trials grants from GSK, Roche, and Qiagen and consultancy fees from GSK, Roche, Merck, Takeda, Exevir, and Allovir. A.H. has received clinical trial grants from Merck and Qiagen and consultancy fees from Merck, Takeda, and Eurofins-Viracor. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log 10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). Vaccination may mitigate this risk; however, immunogenicity appears to be significantly impaired, with reports of increased risk of breakthrough infection. It is unknown if vaccine breakthrough infections are milder or as severe as infections in unvaccinated patients., Methods: We performed a multicenter matched cohort study between March 2020 and September 2021 to assess influence of COVID-19 vaccination on outcomes of COVID-19 infection. Treatment characteristics and disease severity outcomes were compared on the basis of vaccine status; breakthrough infections versus unvaccinated infections. Variable ratio propensity score matching based on age, sex, transplant type, and number of comorbidities, was used to develop the analytic cohort. Logistic regression was used to assess the influence of vaccination status on the selected outcomes., Results: From a cohort of 511 SOT patients with COVID-19, we matched 77 partially or fully vaccinated patients with 220 unvaccinated patients. Treatment characteristics including use of dexamethasone, remdesivir, and antibiotics did not differ. Vaccinated participants were more likely to receive tocilizumab, 15 of 77 (19.5%) versus 5 of 220 (2.3%), P  < 0.001. Disease severity outcomes including oxygen requirement, mechanical ventilation, and mortality were similar among medically attended vaccine breakthroughs compared with unvaccinated patients., Conclusions: SOT recipients who develop medically attended COVID-19 following 1- or 2-dose vaccination seem to have similar disease severity to unvaccinated patients who develop infection. This is consistent with the requirement that SOT recipients need 3 or more vaccine doses and emphasizes the importance of alternate strategies for this population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)