Vikram, Holenarasipur R.

Abstract Background Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. Methods We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. Results Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1–11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil‐predominant pleocytosis. Almost all patients ( n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa‐2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30‐day mortality rate was 36%. Conclusion Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis. image

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is a potentially deadly infection afflicting the immunocompromised population, including solid organ transplant recipients. Several risk factors have been described, including acute rejection, lymphopenia, and cytomegalovirus (CMV) infection. However, little is known regarding the risk imparted by posttransplant lymphoproliferative disorder (PTLD). Methods We performed a nested case-control study of solid organ transplant recipients diagnosed with PCP from 2000-2020. PCP was defined as positive smear or polymerase chain reaction testing with compatible clinical symptoms and radiographic findings. Two control were matched to each case by year of first transplant, first transplanted organ, and sex. Each control had at least as much follow-up from their transplant date to their matched case’s PCP diagnosis date. Multivariable conditional logistic regression was performed to analyze theorized risk factors. Results Sixty-seven cases met inclusion criteria and were matched to 134 controls (Table 1). Median age was 60.9 years, and the most common transplant type was kidney (52.2%). Fourteen patients had a history of PTLD, 12 of which developed PCP. All cases of PTLD were monomorphic, 6 were EBV-positive, 9 were receiving chemotherapy at the index date, and only 1 control patient was receiving PCP prophylaxis. The cases with PTLD developed PCP a median of 85 days after PTLD diagnosis, while the two controls were diagnosed more than 1 year earlier. After adjusting for age, acute rejection requiring treatment within the last 6 months, CMV infection within 6 months, current PCP prophylaxis, and lymphopenia (lymphocyte count < 0.5 x109/L) within 6 months, PTLD had a significant association with PCP (OR 14.0, 95% CI 1.7-114.5; p = .014). Lymphopenia was also associated with PCP (OR 8.2, 95% CI 3.2-20.7; p < .001), while the other factors were not. Table 1:Characteristics of 67 Solid Organ Transplant Recipients with Pneumocystis Pneumonia and 134 Matched Controls Conclusion Diagnosis of PTLD is independently associated with subsequent PCP after adjustment for recognized risk factors. This association is likely influenced by PTLD-directed chemotherapy, particularly regimens containing rituximab. PCP prophylaxis should be initiated in solid organ transplant recipients with PTLD, particularly those undergoing active therapy, and those with severe lymphopenia. Disclosures All Authors: No reported disclosures.

Abstract Background While numerous, most described cases of myocarditis and pericarditis following COVID-19 vaccination are mild and self-limited. We present two cases of life-threatening cardiac tamponade following COVID-19 vaccination. Methods Two cases of cardiac tamponade in temporal association with COVID-19 vaccination were reviewed Results Case 1 : 75-year-old male with rheumatoid arthritis admitted with chest pressure and hypotension 2 days after his 1st dose of Pfizer-BioNTech COVID-19 vaccine. Pericardiocentesis removed 275 ml of exudative effusion with 14,140 nucleated cells/ml. Fluid bacterial and fungal cultures were negative; cytology was inconsistent with malignancy. He had no Epstein-Barr virus (EBV) or cytomegalovirus (CMV) viremia. Symptoms resolved on prednisone and colchicine. A week later, he had an uneventful second COVID-19 vaccine. He went on to have 3 recurrences of pericarditis starting two months after his first. One was within 48 hours of his COVID-19 booster. He is on long term prednisone. Case 2: 66-year-old male with non-Hodgkin’s lymphoma in remission. He developed chest pain a day after his 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Admitted 4 days later with pericardial effusion and managed medically. Readmitted a week later with fever and chest pain. Echocardiogram now showed cardiac tamponade. Pericardiocentesis removed 400 ml of exudative fluid with 1,191 nucleated cells/mL. Cultures for bacteria, fungi, and mycobacteria were negative. Cytology didn't show malignancy. Serologies for CMV, EBV and parvovirus represented past infection. He was discharged with a pericardial drain, colchicine, and NSAIDs. He was later readmitted with fevers. Echocardiogram only showed small pericardial effusion, which did not require drainage. Figure 1Circumferential pericardial effusion seen on trans-thoracic echocardiography from patient in case 1. Conclusion Given the proximity to COVID-19 vaccination and lack of alternative explanations, we believe that tamponade was a direct result of post-vaccine inflammatory pericarditis. Neither patient had a prior history of pericardial effusion. Both tested negative for SARS-CoV-2 by nasopharyngeal swab excluding active infection. Healthcare providers should consider the possibility of pericardial effusion and tamponade in patients with chest pain, shortness of breath, or hypotension following COVID-19 vaccination. Disclosures All Authors: No reported disclosures.

Abstract Background Despite the increasing incidence of neuroinvasive West Nile virus (NiWNV) infection in the US, the spectrum of disease characteristics and neuroimaging findings in immunosuppressed (IS) individuals are not adequately described. We aimed to compare the clinical characteristics and outcomes of NiWNV infection in IS and immunocompetent (IC) patients. Methods We extracted relevant data from all NiWNV patients hospitalized 7/2003-10/2021 at Mayo Clinic hospitals. Cohort was inclusive of patients from the recent historic WNV outbreak in Arizona in 2021. Chi-Square or Kruskal-Wallis and logistic regression were used to compare relevant variables and determine predictors of mortality respectively. Results We included 115 patients (72 IC and 43 IS), mean age 63.5 years; neurologic syndromes included meningoencephalitis (85.2%), encephalomyelitis (8.7%) and myeloradiculitis (6.1%). Presenting symptoms were malaise (72%), fever (66%), altered mentation (64%), gastrointestinal (47%) and myalgia (35.7%). MRI brain was abnormal in 62.8% (49/78), demonstrating T2/FLAIR hyperintensities in 47.4% (brainstem, thalamus, temporal lobes), leptomeningeal enhancement (16.7%) and diffusion restriction (20.5%). Altered mental status (76.7% vs 56.9%), myalgia (44.4% vs. 20.9%), myoclonus (18.6% vs. 4.2%) and thalamic MRI T2 FLAIR abnormalities (11.4% vs 0%) were more common in IS patients. Higher CSF WBC counts were observed in IC vs IS patients (P< 0.05). Immunosuppressed patients were more likely to be treated with intravenous immunoglobulin (44.2% vs 8.3% p=< 0.001) and/or interferon therapy (32.6% vs 6.9%, p=0.0003) and had increased odds of 90-day mortality on multivariable analysis (Adjusted Odds Ratio, AOR 2.22; 95% CI 1.065-4.627, p=0.0334). In the IS subgroup, ICU admission, mechanical ventilation, and Glasgow coma scale of < 8 were associated with reduced overall survival/increased 90-day mortality (p< 0.005). Conclusion Individuals presenting in summer/fall months with the aforementioned symptoms and/or MRI abnormalities should be evaluated for NiWNV infection. Compared to the immunocompetent, immunosuppressed patients with NiWNV are at a significantly greater mortality risk. Novel and effective antiviral therapies aimed at improving outcomes are warranted. Disclosures All Authors: No reported disclosures.

Abstract Background Eculizumab, an inhibitor of terminal complement activation, has been utilized in pre-transplant desensitization, treatment of antibody-mediated rejection and thrombotic microangiopathy in solid organ transplant recipients (SOTR). Eculizumab is associated with meningococcal disease, leading to guidelines for vaccination against serogroups ACWY (menACWY) and B (menB) at least 2 weeks prior to eculizumab therapy. In persons requiring emergent use of eculizumab, prophylaxis for at least 2 weeks is recommended. SOTRs respond suboptimally to vaccination, raising consideration for pre-transplant vaccination and prolonged prophylaxis in those undergoing eculizumab therapy. We sought to describe meningococcal vaccination and prophylaxis practices among SOTRs receiving eculizumab. Methods We performed a retrospective chart review of meningococcal vaccination, including number and timing pre- or post-transplant, along with prophylaxis prescribing and duration in SOTRs receiving eculizumab across 3 distinct Mayo Clinic Enterprise sites (Rochester, Arizona, and Florida). Results 200 SOTRs receiving at least one dose of eculizumab between 1/1/2008 and 9/16/2021 were reviewed. Eculizumab indications included antibody mediated rejection (38%), desensitization (26%), and thrombotic microangiopathy (19%). 83% (166/200) of SOTRs received eculizumab for an unanticipated post-transplant complication. Vaccination rates were 82% (164/200) and 35.5% (71/200) for menACWY dose 1 and 2, respectively, and 54% (108/200) and 28.5% (57/200) for menB dose 1 and 2, respectively. The majority received their first vaccination post-transplant: menACWY 66.5% (133/200) and menB 2.5% (185/200). Among those without vaccination pre-eculizumab, 22.3% (41/184) were not prescribed prophylaxis. The median duration of prophylaxis was 62 (range 4-2651) days. Conclusion Most SOTRs underwent meningococcal vaccinations near the time of eculizumab administration post-transplant for an unanticipated complication. One-fifth of those meeting criteria were not provided meningococcal prophylaxis. These findings may support pre-transplant administration of meningococcal vaccinations and heightened awareness for meningococcal prophylaxis in SOTRs receiving eculizumab. Disclosures All Authors: No reported disclosures.

AbstractIntroductionInfections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection.MethodsThis is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment.ResultsWe identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients.ConclusionsInfections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. image

The COVID-19 pandemic has disrupted medical care worldwide and caused delays in care for many illnesses and procedures unrelated to COVID-19; however, less clear is how it may have affected diagnosis of conditions that present with similar symptoms, such as primary pulmonary coccidioidomycosis (PPC). We conducted an observational cohort study of patients diagnosed with PPC between March 1 and December 1 in 2 years: 2019 (before COVID-19) and in 2020 (after COVID-19) to compare the time from symptom onset to PPC diagnosis. Relevant demographic and clinical variables were collected, and statistical analyses were performed with the χ 2 test, Wilcoxon rank sum test, and Cox proportional hazards regression analysis. During 2019, 83 patients were diagnosed with PPC. During 2020, 113 patients were diagnosed with PPC. For both groups, the median time from symptom onset to diagnosis of PPC was 14 days (P = .13). No significant differences in time to diagnosis existed between the 2 years for location of diagnosis (outpatient clinic, emergency department, or in hospital), for computed tomographic imaging performed before diagnosis, or for number of COVID-19 tests received before PPC diagnosis. In addition, there were no differences in the 2 years between the total number of clinical visits before diagnosis. However, patients in the post-COVID-19 group who had fever were diagnosed with PPC earlier than those without fever (hazard ratio, 1.77; 95% confidence interval, 1.15–2.73; P = .01). Contrary to what we expected, no significant delay in diagnosis of PPC occurred during the COVID-19 pandemic.

Background. The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. Methods. Abdominal solid organs from SARS-CoV-2–infected donors were transplanted into uninfected recipients. Results. Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2–infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. Conclusions. Transplanting nonlung organs from SARS-CoV-2–infected donors into uninfected recipients demonstrated no evidence of virus transmission.

Abstract Background Despite the endemic nature of Coccidioides sp. to the American Southwest, the incidence Coccidioides sp. infective endocarditis (CIE) is rare. Following successful treatment of a patient with CIE at our institution, we reviewed the literature to identify trends in disease presentation, patient characteristics, and outcomes. Methods We reviewed all cases of CIE reported since 1938. Details including patient demographics, underlying immunodeficiency, time to diagnosis, treatment, and outcome were collected for analysis of diagnostic challenges and survival. Results Including ours, we identified 11 published cases of CIE. The majority (7) occurred in men. 5 patients were of either African American or Hispanic descent. Of the 10 patients with reported ages, the median age was 35.5 years (range 3 weeks – 61 years). 5 patients had a previous diagnosis of coccidioidomycosis and only 3 had an immunocompromising condition. These comprised pregnancy, heart transplant, and juvenile inflammatory arthritis. Three cases had multi-valvular involvement, but the majority affected the mitral (5) and the aortic (4) valves. Only 2 of the 11 cases involved a prosthetic valve. Of the 8 cases with reported blood cultures, only 2 were positive. Ten of the 11 cases had extra-cardiac disease. Complement fixation (CF) titers were heterogenous with a median of 1:32 and a range of 1:1 to 1:2048. There was no obvious correlation between a patient’s CF titer and their survival. Average time to diagnosis was 3.5 months (range 2.5 – 36 months). Diagnosis was made post-mortem in 4 of the 11 cases. 6 patients (54%) did not survive. Notably, 2 of the fatal cases preceded the discovery of amphotericin B (1969) and 4 occurred prior to the discovery of fluconazole (1990). Of the five patients that survived, four required surgical intervention in addition to azole therapy. Conclusion CIE is a diagnostic and therapeutic challenge. The diagnosis itself is rare, culture incubation times are long, and the symptoms are often non-specific thus delaying definitive therapy. The introduction of azole therapy appears to have had significant impact on rates of survival. Despite this, successful management of CIE still requires concurrent surgical intervention with aggressive, indefinite anti-fungal therapy. Disclosures All Authors: No reported disclosures