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ABSTRACT Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (“vax-plasma”). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% ( P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization. IMPORTANCE As SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Abstract We studied patients diagnosed with aspergillosis based on positive bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) who had follow-up BAL sampling within 180 days. GM trend and clinical outcome were concordant in only 60% (30/50). While useful for the initial diagnosis, BAL GM trending does not always correlate with treatment response.

AbstractBackgroundGeographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation, and outcomes of 5 endemic mycoses in SOT recipients.MethodsMultiple databases were reviewed from inception through May 2023 using key words for endemic fungi (eg, coccidioidomycosis or Coccidioides, histoplasmosis or Histoplasma, etc). We included adult SOT recipients and publications in English or with English translation.ResultsAmong 16 cohort studies that reported on blastomycosis (n = 3), coccidioidomycosis (n = 5), histoplasmosis (n = 4), and various endemic mycoses (n = 4), the incidence rates varied, as follows: coccidioidomycosis, 1.2%–5.8%; blastomycosis, 0.14%–0.99%; and histoplasmosis, 0.4%–1.1%. There were 204 reports describing 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis cases. The majority of patients were male (176 of 261 [67.4%]). Transplanted allografts were mostly kidney (192 of 268 [71.6%]), followed by liver (n = 39 [14.6%]), heart (n = 18 [6.7%]), lung (n = 13 [4.9%]), and combined kidney-liver and kidney-pancreas (n = 6 [2.7%]). In all 5 endemic mycoses, most patients presented with fever (162 of 232 [69.8%]) and disseminated disease (179 of 268 [66.8%]). Cytopenias were frequently reported for histoplasmosis (71 of 91 [78.0%]), coccidioidomycosis (8 of 11 [72.7%]) and talaromycosis (7 of 8 [87.5%]). Graft loss was reported in 12 of 136 patients (8.8%). Death from all-causes was reported in 71 of 267 (26.6%); half of the deaths (n = 34 [50%]) were related to the underlying mycoses.ConclusionsEndemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high all-cause mortality rate, including many deaths that were attributed to endemic mycoses.

Abstract The Infectious Diseases Society of America Training Program Directors Committee met in October 2022 and discussed an observed increase in clinical volume and acuity on infectious diseases (ID) services, and its impact on fellow education. Committee members sought to develop specific goals and strategies related to improving training program culture, preserving quality education on inpatient consult services and in the clinic, and negotiating change at the annual IDWeek Training Program Director meeting. This paper outlines a presentation of ideas brought forth at the meeting and is meant to serve as a reference document for infectious diseases training program directors seeking guidance in this area.

Abstract Background Letermovir (LTMV) is approved for CMV prophylaxis during the first 100 days after HSCT. Thereafter, CMV reactivation (CMVr) may still occur. This study aims to evaluate the incidence and risk factors for any CMVr and clinically significant CMV infection (csCMVi) in patients who received LTMV prophylaxis. Methods Retrospective multicenter cohort study of HSCT patients who received 100 days of LTMV prophylaxis from 08/2018 to 09/2022. Categorical and continuous variables were compared with Fisher’s exact and Kruskal-Wallis test respectively. Logistic regression was used to identify risk factors. Results Of 115 HSCT patients, 28 had CMVr after LTMV prophylaxis (Table 1), including 21 with csCMVi (Table 2). Of note, 29 (25.2%) patients had breakthrough CMV during LTMV prophylaxis. Among 28 cases of post-LTMV CMVr, DNAemia occurred with a median of 38.5 (31.3 – 47) days after stopping LTMV. The median absolute lymphocyte count (ALC) at diagnosis was 1.29 (0.41 – 2.04) x109cells/L. Median peak CMV DNAemia at was 482 (100.5 – 2600) IU/mL, with a duration of 29 (20- 35) days; none had end organ disease. All were receiving immunosuppression for graft-versus-host disease treatment (n=18) or prophylaxis (n=10). Risk factors for CMVr and csCMVi are listed in Table 3. For CMVr, univariate analysis showed that CMV D-/R+ status is associated with increased risk, while having CMV D+ donors or acute myeloid leukemia (AML) had lower risk. Multivariable analysis showed D-/R+ status and breakthrough viremia while on LTMV were associated with increased risk. csCMVi in 21 patients were treated with valganciclovir (n=15) or IV ganciclovir (n=6) for a median duration of 37 (25.5 – 50) days. Univariate analysis showed that acute lymphoblastic leukemia (ALL) and reduced intensity conditioning were associated with increased risk, while AML had lower risk of csCMVi. On multivariable analysis, ALL, and D-/R+ had higher risk while AML had lower risk. Demographics and clinical characteristics of allogeneic hematopoietic stem cell recipients with or without late clinically significant CMV infection Conclusion One in four allogeneic HSCT patients who received LTMV developed post-prophylaxis CMVr within 100 to 200 days post-transplant. CMV D-/R+ status had a higher risk for CMVr and csCMVi after LTMV discontinuation. Patients with AML had a lower risk for CMVr and csCMVi. Disclosures Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Cytomegalovirus (CMV) infects millions in the US and is a source of comorbidity among immunocompromised patients. Despite its prevalence, there is limited data on clinical characteristics or outcomes among HIV-negative, non-transplant (NHNT) patients in population-based cohorts. We aim to evaluate a multicenter US-based network to obtain clinical characteristics and outcomes of NHNT patients with CMV disease and explore potential prognostic clinical characteristics implicated in increased morbidity and mortality. Methods This is a US-based multicenter, population-based, retrospective cohort study. We queried TrinetX, a global research network, to identify patients with a CMV disease by ICD-10-CM codes and serum and PCR > 5000 IU/mL. We captured comorbidities diagnosed within 90 days of CMV infection diagnosis, symptoms noted within 30 days, and outcomes of interest at 30 days and 1 year. Primary outcome was all-cause mortality. Secondary outcomes were hospitalization and CMV disease-related complications. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 90 days. Results We found 1123 patients with evidence of CMV disease. The mean patient age was 53 years, 48% men and 50% white. Aplastic anemia and neoplasms were the most common comorbidities (Table 1). Thromboembolism was a common complication (15%). Half of the patients had dyspnea, fever, abdominal pain, and nausea. CMV disease was associated with 14%, 22%, and 26% mortality at 30 days, 90 days, and one year, respectively. 35% of patients required hospitalization within 30 days. After propensity score matching, we had 278 patients in each cohort. Dyspnea and weakness were linked to increased 90-day mortality (Figure 1). Purpura, encephalopathy, and sepsis were more common in patients who died. High CMV serum viral load and ferritin were associated with increased mortality. Conclusion NHNT patients with CMV disease often have underlying comorbidity, commonly aplastic anemia, and neoplasms. CMV disease was associated with thrombosis and a high risk of hospitalization and mortality. Vascular disease, sepsis, high viral load, and cell lysis markers were prognostic factors for mortality in this cohort. Disclosures Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared. Methods This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Results Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups. Conclusion This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In prior work, those who continued remdesivir in an outpatient setting had better outcomes. Here, we assessed patients’ perspectives and the economic impact of this outpatient practice. Methods During a one-year period, 3,029 patients received remdesivir for COVID-19 in the hospital; of them, 542 were dismissed to continue remdesivir in the outpatient setting and were surveyed. The cost of care was compared between those who remained in the hospital vs. those who were dismissed. Results 470 of 542 patients were surveyed, and 93 (19.8%) responded. Responders were older than non-responders (median, 63 vs. 58 years). The majority (70.5%) had symptoms resolved by the time of the survey. Ten patients (11.4%) had persistent symptoms attributed to long COVID-19, including fatigue (30.1%), brain fog (23.7%), and insomnia (18.3%). 73.8% were excited to learn about the outpatient remdesivir program. The majority (81.0%) felt that receiving therapy at home was the right decision; 79.5% had support and felt the benefits of completing treatment at home. The majority were satisfied with communication before (75.6%) and during (80.5%) the outpatient appointment, information on benefits (80.3%) and risks (58.5%), time spent at the infusion center (88.6%), quality of care (82.3%) and overall experience (76.0%). The benefits of treatment were high-value (82.6%), while the infusions' cost, inconvenience, and discomfort were unimportant for most responders. After adjusting for gender, comorbidity score, and WHO scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p< .01). During this study, we estimated a total of 1,077 hospital room-days were made available to other patients. Conclusion An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients hospitalized for COVID-19. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital rooms for other patients needing critical services. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Bijan J. Borah, Ph.D., Boehringer Ingelheim: Advisor/Consultant|Exact Sciences: Advisor/Consultant Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support