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Abstract Background Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). As a lack of immunity predisposes to infection, a laboratory test that measures CMV-specific cell-mediated immunity (CMV CMI) may help guide antiviral prophylaxis, predict relapses and correlate with outcomes. We assessed CMV CMI in CMV D+/R- patients during valganciclovir primary prophylaxis and in CMV viremic SOTRs during antiviral treatment, and correlated the results with post-prophylaxis CMV infection and post-treatment relapse, respectively. Methods CMV CMI was assessed in two groups of SOTRs using the QuantiFERON© CMV interferon-gamma release assay (IGRA), with level >0.2 IU/mL suggestive of immunity. The first group included CMV D+/R- SOTRs who underwent monthly CMV CMI testing during 6 months of valganciclovir prophylaxis. These patients were prospectively followed for CMV episodes for 1 year post transplant. The second group included SOTRs with CMV viremia or disease, who underwent CMV CMI testing at time of CMV diagnosis and at various time points during antiviral treatment. These patients were prospectively followed for CMV relapse for 1 year post-primary CMV episode. Standard definitions were used to define CMV infection and disease. Results In the primary prophylaxis cohort, 24 CMV mismatched (D+/R-) SOTRs were enrolled. Only 1 patient (4.2%) demonstrated a CMV CMI >0.2 IU/mL by the end of prophylaxis; this patient did not develop CMV disease. Four (16.6%) patients developed post-prophylaxis CMV infection, none of which had CMV CMI >0.2 IU/ml. In the post-treatment cohort, 20 CMV viremic SOTRs were enrolled, including 12 D+/R- (60%). Eighteen (90%) had CMV CMI levels >0.2 IU/mL by end of treatment and none developed CMV relapse. In contrast, the single patient who relapsed after treatment had a CMV CMI response < 0.2 IU/ml (p=0.05). Conclusion CMV D+/R- SOTRs are unlikely to develop CMV CMI during valganciclovir prophylaxis. Thus, the utility of CMV CMI for risk stratification of post-prophylaxis CMV infection in CMV D+/R- SOTRs is questionable. Conversely, CMV CMI testing may potentially be a useful marker of CMV relapse risk after treatment and guide the role of secondary antiviral prophylaxis. Disclosures Elitza Theel, PhD, D(ABMM), Euroimmun US: Advisor/Consultant|Oxford Immunotech: Advisor/Consultant|Roche Diagnostics: Advisor/Consultant|Serimmune Inc: Advisor/Consultant Raymund R. Razonable, MD, American Society of Transplantation: Board Member|gilead: Grant/Research Support|novartis: DSMB|regeneron: Grant/Research Support|Roche: Grant/Research Support.

Purpose of review Coronavirus disease-2019 (COVID-19) disproportionately causes severe outcomes in solid organ transplant recipients (SOTR). Antispike monoclonal antibodies have been authorized for therapy and prophylaxis for COVID-19. Here, we review the current state of antispike monoclonal antibodies and their role for SOTRs. Recent findings Bamlanivimab with or without etesevimab, casirivimab-imdevimab and sotrovimab have reduced the rates of hospitalization and severe disease in high-risk patients with mild-to-moderate COVID-19. Multiple retrospective studies have also demonstrated monoclonal antibodies are effective in SOTR populations. However, the evolution of resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns has resulted in revocation of the authorization of bamlanivimab with or without etesevimab, and casirivimab-imdevimab as treatment and postexposure prophylaxis (PEP). Sotrovimab and bebtelovimab are currently authorized for treatment of the predominant circulating SARS-CoV-2 B.1.1.529 (Omicron), but not as pre or PEP. Tixagevimab–cilgavimab, a long-acting antibody combination preparation, is authorized for preexposure prophylaxis in high-risk immunocompromised populations, including SOTRs, who are less likely to mount an effective immune response following vaccination series and booster. Summary Antispike monoclonal antibodies are useful for the prevention and treatment of mild-to-moderate COVID-19 in SOTRs. However, their clinical use should be determined by the evolving epidemiology of SARS-CoV-2 variants in the community.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from 11/6/2020 to 11/5/2021 at one of the Mayo Clinic hospitals. Results: Among 3,029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended the five-day course. Among them, 2,169 (80%) completed treatment during hospitalization, while 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p<0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p=0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p<0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Abstract Background Antispike monoclonal antibodies are recommended for early treatment of high-risk persons with mild to moderate coronavirus disease 2019 (COVID-19). However, clinical outcomes of their use during the severe acute respiratory syndrome coronavirus 2 Omicron wave are limited. Methods This is a descriptive retrospective study of high-risk adult patients who received treatment with sotrovimab (January 1–March 20, 2022) or bebtelovimab (March 21–April 30, 2022). The primary outcome was the proportion of patients who progressed to severe outcome within 30 days after receiving antispike-neutralizing monoclonal antibody infusion. Results A total of 3872 high-risk patients (median age, 62.7 years; 41.1% male) with mild to moderate COVID-19 received sotrovimab (n = 2182) or bebtelovimab (n = 1690). Among sotrovimab-treated patients, the most common comorbidities were an immunosuppressed condition (46.7%), hypertension (38.2%), and diabetes (21.2%). The rates of severe outcome, intensive care unit (ICU) admission, and mortality were 2.2%, 1.0%, and 0.4%, respectively, after sotrovimab infusion. Among bebtelovimab-treated patients, the most common comorbidities were hypertension (42.7%), diabetes (17.1%), and an immunosuppressed condition (17.0%). The rates of severe disease, ICU admission, and mortality were 1.3%, 0.5%, and 0.2%, respectively, after bebtelovimab infusion. Older age, immunosuppressed status, and several comorbidities were associated with severe disease progression, while COVID-19 vaccination was associated with lower risk. No anaphylaxis was reported during monoclonal antibody infusion. Conclusions This real-world analysis of a large cohort of high-risk patients demonstrates low rates of severe disease after treatment with sotrovimab during the era dominated by Omicron B.1.1.529 and after treatment with bebtelovimab during the era dominated by BA.2 and Omicron subvariants.

Abstract The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%–1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%–1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Abstract Background We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation. Methods CINAHL, PUBMED, and OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation. Results Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14–417) and 8.8 (range, 0–208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 [79.6%]), while skin rash (22/108 [20.3%]) and fever (31/103 [30%]) were less common. Peripheral eosinophilia was observed in half of patients (41/77 [53.2%]). Bacteremia (31/59 [52.5%]) was frequently due to Gram‐negative organisms (24/31 [77.4%]). Abnormal chest radiologic findings were reported in half (56/108 [51.9%]). The majority had hyperinfection syndrome (97/108 [89.8%]) while disseminated strongyloidiasis was less common (11/108 [10.2%]). Thirty‐two cases were categorized as donor‐derived infection (DDI), with donors (23/24 [95.8%]) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5–34.3 weeks) after transplantation. Treatment consisted of ivermectin ( n = 26), a benzimidazole ( n = 27), or both drugs ( n = 28). There was high all‐cause mortality (48/107, 44.9%) and a high Strongyloides ‐attributable mortality (32/49, 65.3%). Conclusions Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro‐active screening is needed, to ensure preventive measures are provided to recipients at increased risk.

Abstract Background Solid organ transplant recipients (SOTRs) are at high‐risk for severe infection from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Anti‐spike monoclonal antibodies are currently utilized under emergency use authorization to prevent hospitalization in high‐risk individuals with coronavirus disease 2019 (COVID‐19), including SOTRs. However, clinical data for bebtelovimab, the sole currently available anti‐spike monoclonal antibody for COVID‐19, is limited. Methods We conducted a retrospective cohort study of adult SOTRs diagnosed with mild‐to‐moderate COVID‐19 from January 2022 through May 2022 who received either bebtelovimab or sotrovimab. The primary outcome was COVID‐19‐related hospitalization within 30 days of COVID‐19 diagnosis. Data were analyzed with Fisher's exact test. Results Among 361 SOTRs, 92 (25.5%) received bebtelovimab and 269 (74.5%) received sotrovimab. The most common organ transplant was a kidney (42.4%). SOTRs who received bebtelovimab had a higher proportion who had received a booster SARS‐CoV‐2 vaccine dose and had received their last vaccination dose more recently. Eleven (3.0%) SOTRs were hospitalized, and rates of hospitalization were similar between monoclonal antibody groups (3.3% versus 3.0%; p > .99). Three patients required admission to an intensive care unit, all of who received sotrovimab. Four (1.1%) patients died within 30 days of COVID‐19 diagnosis, two from each group. Conclusions SOTRs with mild‐to‐moderate COVID‐19 who received bebtelovimab had similar rates of COVID‐19‐related hospitalization as those who received sotrovimab. While differences in vaccination rates and viral subvariants could act as confounders, bebtelovimab appears to be of similar effectiveness as sotrovimab. image