LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

A Case Report Of The Effects Of Chemotherapy On Post-heart-transplant Gene Expression Profiling

Introduction: Malignancies are a major complication of heart transplant (HT). Noninvasive surveillance after HT using gene expression (GEP) profiling and donor derived cell free DNA (dd-cfDNA) are noninferior to biopsy and are widely utilized. The interpretation of % dd-cfDNA, is not well understood in malignancies with a conceptual increase in the recipient fraction. The effect of chemotherapy on GEP in the setting of post-HT surveillance has not been described to the best of our knowledge. Hypothesis: Induction of chemotherapy will cause global transcriptional reduction in GEP. Method(s): GEP was performed with AlloMap (AM, CareDx), which evaluates expression levels of 11 mononuclear cell genes, involved in lymphocyte activation, T-cell priming, cell migration, hematopoietic proliferation, steroid sensitivity, and platelet activation. Scores range from 0-40, higher scores have a stronger correlation with rejection. At our center a total of 995 draws were analyzed from 2019-2022. In parallel dd-cfDNA, which informs about graft injury was analyzed using AlloSure (AS, CareDx). Case Events: A 71-year-old male HT recipient for nonischemic cardiomyopathy and no rejection history was diagnosed with metastatic gastric adenocarcinoma at 16 months post-HT. Following diagnosis, mycophenolic acid was stopped, prednisone 5 mg was started, and tacrolimus trough goal was gradually lowered to 4-6 given infectious complications. Palliative chemotherapy with folinic acid, fluorouracil (5-FU), oxaliplatin (FOLFOX) was initiated at 18 months post-HT with planned dose reduction of oxaliplatin and holding of 5-FU bolus to reduce risk of myelosuppression given comorbidities. Oxaliplatin was stopped at 18 months post HT. Due to COVID he last received 5-FU at 33 months post-HT. Graft function remained stable and DSA negative. At 36 months post-HT, he developed a bowel obstruction without surgical options for interventions and expired shortly thereafter. Result(s): With initiation of prednisone and following chemotherapy there was a drastic decrease in AM scores (Fig. A). Steroid therapy led to an 18% decline in AM scores, the greatest decrease occurred with chemotherapy, with 67% decline from the mean when compared to all center patients (Fig B). Dd-cfDNA levels remained stable during the course aside from one early elevation. Conclusion(s): To the best of our knowledge this is the first published case on the effect of chemotherapy on GEP profiling in the setting of post-HT surveillance. This case advises caution when interpreting GEP in the setting of chemotherapy showing great reduction in GEP scores. While dd-cfDNA levels remained relatively stable after malignancy diagnosis and treatment initiation further studies will need to inform on the use of both GEP and dd-cfDNA in these patients.Copyright © 2022

Kidney Limited Complement-Mediated Thrombotic Microangiopathy- a Challenging Case

Introduction: Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare disease characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and organ injury. The absence of hemolysis and thrombocytopenia is rare. We present a case of kidney limited CM-TMA successfully treated with eculizumab. Method(s): A 36 year-old man with poorly controlled hypertension, obesity, CKD (baseline creatinine (sCr) 2,6mg/dL, albuminuria 150mg/g), hyperlipidemia, obstructive sleep apnea, hyperuricemia, SARS-CoV-2 infection 3 months earlier, and family history of CKD of unknown etiology (father started kidney replacement therapy (KRT) at young age) presented to the ER with high blood pressure and right hemiplegy. Head CT scan showed left thalamo-capsular hemorrhage. Oftalmologic exam was normal. Laboratory findings were: hemoglobin (Hb) 12.5g/dL, elevated white cell count (17.900/uL), platelet count 214.000/uL, sCr 4.3mg/dL, lactate dehydrogenase (LDH) 303U/L. Urine dipstick revealed protein+ and Hb++. Chest X-ray showed signs of pneumonia. The patient was admitted in ICU and mechanically ventilated. After 3 weeks, renal function recovered to its baseline (sCr 1.5mg/dL, no proteinuria) without KRT, and the patient was transferred to the medical ward. Several infectious complications prolonged hospital stay. After 3 months, a new mild SARS-CoV-2 infection was detected. At this time: Hb 9.9g/dL, platelets 220.000/uL, sCr 2.2mg/dL. Six days later the patient showed Hb 9.5 g/dL, without reticulocytosis, platelets 195.000/uL, sCr 6.3mg/dL, LDH 348U/L, normal haptoglobin, no schizocytes on blood smear. After 3 days, the patient was anuric and sCr increased to 10mg/dL, prompting KRT. Kidney ultrasound showed no abnormalities. Autoimmunity study was negative, normal C3/C4, no monoclonal gammopathy, and negative viral serologies. Kidney biopsy (KB) was performed as the etiology of AKI remained unclear. Light microscopy revealed thickned glomerular capillary walls with subendothelial expansion forming double contouring, arteriolar intimal expansion and fibrin thrombi occluding the vascular lumina. Scarse C3 deposition was observed in capillary walls. Since the morphological features were consistent with TMA, secondary causes were excluded and primary causes also investigated: ADAMTS13 activity, complement factor B and I were within normal range, slight decrease of factor H with normal anti factor H antibody. The molecular studies of complement genes were performed by NGS-based gene panel revealing a rare heterozygous missense mutation on gene CFB, c.1189G>A (p.Asp397Asn), described as a genetic risk factor of CM-TMA in the presence of a trigger. Result(s): Treatment with eculizumab was started and the patient showed signs of kidney recovery allowing KRT suspension 1 month later (sCr 5.53mg/dL). Of note, the patient never presented MAHA or thrombocytopenia. After 5 months, renal function improved to sCr 3.9mg/dL. Conclusion(s): We report a case of CM-TMA with isolated kidney injury without laboratory hallmarks of TMA. Patients usually require a secondary trigger for the disease to manifest, and in this case SARS-CoV-2 infection may have been the causative agent. A mutation in gene CFB may have predisposed the patient to the outcome. KB was crucial for diagnosis and prompted the treatment with eculizumab with partial recovery without the need for chronic KRT. No conflict of interestCopyright © 2023

Can SARSCov2 infection drive in an acute rejection in lung transplant recipients?

Objective: to describe the clinical presentation and outcomes of COVID-19 in lung transplant recipients (LTRs) when managed with high-dose corticosteroids along with standard therapy. Method(s): all nine (9) adult LTRs with confirmed SARS-CoV-2 infection and chest X-ray with predominant bilateral infiltrates and hypoxemia, treated with high-doses corticosteroids similar to an acute rejection treatment were included. All our treated patients presented acute respiratory failure and bilateral pulmonary infiltrates. Result(s): six (6) out of nine (9) patients (66%) treated with bolus evolved favorably. Patients without corticosteroids treatment and severe disease died. Despite lymphopenia and methylprednisolone pulse therapy there were no infectious complications. As per protocol antiviral, bacterial and fungal prophylaxis was prescribed during this period. RT- PCR took long time in becoming negative. Patients who received megadoses of corticosteroids were more likely to live than those who received low doses Conclusion(s): COVID-19 in lung transplant recipients with acute respiratory failure presents a favorable outcome when is managed with high-doses corticosteroids along with standard therapy.

A CASE OF LONG-TERM TOLERANCE AFTER KIDNEY TRANSPLANTATION.

We present a case of long-term organ functioning (ca.10 years) after allografting of a cadaveric kidney without usage of immunosuppressing drugs. In 2005, a patient suffering from a hypertensive form of chronic glomerulonephritis, have received an allogeneic graft of cadaveric kidney compatible for AB0 system, HLA antigens (A19, B07, DR04), and negative results of cross-match test. The graft function was immediately restored, with normalization of creatinine levels achieved 4-5 days after surgery. Immunosuppression with cyclosporine, solumedrol, cellcept, metypred and simulect was performed in the hospital. Pulse therapy with solumedrol was performed on the day +20 due to the development of initial rejection signs. The postoperative period proceeded without infectious complications. The patient was discharged being recommended to take cyclosporine, Cell-Sept and Metypred. Within a year after transplantation, the patient claimed for pain in the hip joint, and, therefore, metypred was completely canceled. Subsequently, the Cellcept was replaced with a Mayfortic. In 2007, the signs of coxarthrosis were revealed at computed tomography, followed by aseptic necrosis of the the right femur head. Deforming osteoarthritis of the right hip joint was detected, and the hip replacement surgery was suggested. In 2010, due to risk of side effects from ongoing immunosuppressive therapy, e.g., joint damage, the Mayfortic was canceled. In 2012, being in fear of original Sandimmun Neoral replacement by a generic drug, the patient completely refused cyclosporine therapy. In 2021, the endoprosthetics of the right hip joint was performed, and the surgical wound healed initially. Since 2012, the patient has not completely taken immunosuppressive therapy. Over this time period, the patient has never been admitted to the hospital for impaired functioning of the organ graft. Meanwhile, he monitored his graft function on regular basis undergoing biochemical analyses, clinical examination, ultrasound studies of the graft and made regular visits to the outpatient department. In 2021, a week after hip replacement, there was a slight increase in serum creatinine, followed by further increase to 230 mmol/L in 2021, and to 310 mmol/L in March 2022. In February 2022, the patient suffered mild respiratory infection (confirmed COVID-19). In March 2022, the first clinical signs of increasing nephropathy appeared, i.e., swelling of both lower extremities, with leukocytes in urine upon routine analysis, increased blood flow resistance in the main artery of the transplant shown by ultrasound study. Due to worsening of the patient's condition, he resumed taking the prescribed immunosuppressants. Copyright © 2022, SPb RAACI.

What Proportion of Infectious Diseases Physicians Have Buprenorphine Waivers to Treat Opioid Use Disorder in the United States?

Background. Since the onset of the COVID-19 pandemic, opioid-related overdose deaths have increased. Buprenorphine, a medication for opioid use disorder (OUD), is safe and effective but is underutilized and requires qualifying physicians to obtain a waiver. Infectious diseases (ID) physicians are uniquely positioned to treat OUD, as persons with OUD may present with infectious complications from injection drug use. We sought to understand the proportion and distribution of ID physicians with waivers in the United States (US). Methods. This was a cross-sectional study merging data from the Centers for Medicare & Medicaid Services and the Drug Enforcement Agency Substance Abuse and Mental Health Services Agency. Our primary outcome was proportion of ID physicians who possess buprenorphine waivers. We used multivariable regression models to identify individual and county-level characteristics associated with buprenorphine waiver possession. We used geospatial analysis to describe county-level distribution of buprenorphine-waivered ID physicians. Results. Among 6439 ID physicians in the US, 170 (2.6%) possessed buprenorphine waivers. Overall, 57.2% of ID physicians were male with a median 23 (IQR 15-33) years since medical school. Most (97.3%) practiced in metropolitan counties. In multivariable analysis, medical school graduation beyond 20 years was associated with lower odds of waiver possession compared to those graduating within 20 years (OR 0.59, 95% CI 0.43-0.80). ID physicians practicing in counties with median income > 50,000/year and in counties with higher proportion of uninsured residents also had lower odds of having a waiver (OR 0.58, 95% CI 0.35-0.97;OR 0.93, 95% CI 0.90-0.97). Among counties with at least one ID physician (n=519), 86.6% had no buprenorphine-waivered ID physicians (Figure 1). Figure 1 County-Level Distribution of Infectious Diseases Physicians with Buprenorphine Waivers Conclusion. Fewer than 3% of ID physicians in the US have obtained waivers to prescribe buprenorphine, highlighting missed opportunities to treat individuals with OUD, especially in rural America. Education on OUD management should be integrated into ID continuing medical education, and policies are urgently needed to expand buprenorphine access to persons without insurance.

Reduction of Rabbit Anti-Thymocyte Globulin Dosing for Induction of Kidney Transplant During the COVID-19 Pandemic

Purpose: Rabbit anti-thymocyte globulin (rATG) is a polyclonal antibody utilized for induction immunosuppression in high immunologic risk kidney transplant recipients. However, the optimal total dose of rATG has not been identified. Higher cumulative doses of rATG may be associated with an increased risk of adverse infectious and hematologic outcomes, while lower cumulative doses may not provide adequate immunosuppression to prevent acute rejection. In March 2020, the total rATG dose in our institution's induction protocol for kidney transplant recipients was reduced from 6 mg/kg to 4.5 mg/kg to avoid potential infectious complications from COVID- 19. The objective of this study is to compare the efficacy and safety between two different doses of rATG. Method(s): This was a single center, retrospective chart review of adult kidney transplant recipients who received rATG for induction between September 1, 2019 and August 31, 2020. Patients who received a total dose of 6 mg/kg rATG were compared to patients who received a total dose of 4.5 mg/kg. The primary outcome was biopsy proven acute rejection (BPAR) within 90 days of transplant. Secondary outcomes assessed incidence of infection, leukopenia, neutropenia, thrombocytopenia, and delayed graft function within 90 days of transplant. Result(s): Eighty-one adult kidney transplant recipients were included in this study;37 received 6 mg/kg of rATG and 44 received 4.5 mg/kg of rATG. Incidence of BPAR was significantly lower in the 6 mg/kg rATG group compared to the 4.5 mg/ kg group (2.7% vs 20.5%, p=0.02). The majority of rejection episodes were classified as borderline. Patients who had BPAR were treated with corticosteroids. The number of patients who had an infection was significantly lower in the 6 mg/kg group compared to 4.5 mg/kg group (21.6% vs 47.7%, p=0.02). There was a numerically lower incidence of delayed graft function in the 6 mg/kg group compared to the 4.5 mg/kg group (25.0% vs 43.2%, p=0.18). Incidence of leukopenia, neutropenia, and thrombocytopenia were similar between groups. Conclusion(s): In conclusion, a lower cumulative dose of rATG was associated with an increased risk of borderline rejection and a numerically higher incidence of delayed graft function.

POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) IN RENAL TRANSPLANT PATIENTS WITH COVID-19

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after transplantation. While there is evidence that hematologic malignancy is associated with increased severity in COVID-19 infection, there is little description of PTLD and COVID-19. CASE PRESENTATION: A 68-year-old man and a 68-year-old female, both of whom had prior renal transplantation, were admitted to the hospital with COVID-19 pneumonia. Both patients were vaccinated against COVID-19, though were negative for spike protein antibodies. The man was treated with remdesivir and the woman was treated with remdesivir and dexamethasone. Both patients improved and were discharged. Within a month, both had recurrent symptoms of dyspnea and fever requiring re-admission. They were hypoxic, the man requiring high flow nasal cannula and the woman requiring nasal cannula to maintain SpO2>90%. They had positive COVID-19 PCR tests, with cycle threshold lower than in their initial admissions, as well as chest imaging with bilateral infiltrates. The man had a pleural effusion with cytology consistent with PTLD and perinephric mass and retroperitoneal lymphadenopathy with biopsy confirming PTLD. The woman had a renal sinus mass with biopsy confirming PTLD. Both patients were treated with another 5 days of remdesivir and started on dexamethasone. The medical team discussed monoclonal antibody treatment, but the patients did not meet EUA criteria and compassionate use request was denied. To treat PTLD, both were initiated on Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP). Since then, both patients have had complicated and prolonged hospital courses. The woman developed renal failure and severe C.diff colitis complicated by toxic megacolon requiring total colectomy. The man developed renal failure, CMV viremia, and pseudomonas UTI. The patients were able to be weaned to room air, though ultimately the woman had to be intubated due to poor mental status and remains on low oxygen settings. Both patients continue to be persistently positive for COVID-19 by PCR. DISCUSSION: This case illustrates diagnosis and treatment of PTLD in two patients with COVID-19 infection. Of particular interest was the use of Rituximab, an anti-CD-20 antibody which impairs humoral immunity, in the treatment of PTLD, as the drug has been associated with increased risk of severe COVID-19 infection. Rituximab was particularly concerning as both patients had persistent COVID-19 without development of immunity despite prior vaccination, and both continue to be positive despite two months of active infection. The patients had improvement of their respiratory status, though have had poor and complicated clinical courses with renal and infectious complications. CONCLUSIONS: Treatment of PTLD in patient's with active COVID-19 may impair ability to clear virus, though impact on outcomes is unclear. Reference #1: Simpson-Yap, S., de Brouwer, E., Kalincik, T., Rijke, N., Hillert, J. A., Walton, C., Edan, G., Moreau, Y., Spelman, T., Geys, L., Parciak, T., Gautrais, C., Lazovski, N., Pirmani, A., Ardeshirdavanai, A., Forsberg, L., Glaser, A., McBurney, R., Schmidt, H., … Peeters, L. (2021). Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis. Neurology, 97(19). https://doi.org/10.1212/WNL.0000000000012753 Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A… Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1). https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Passamonti, F., Cattaneo, C., Arcaini, L. Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., … Corradini, P. (2020). Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. The Lancet Haematology, 7(10). https://doi.org/10.1016/S2352-3026(20)30251-9 DISCLOSURES: No relevant relationships by Ian Mahoney No relevant relationships by Caroline Motschwiller

COURSE AND OUTCOMES OF COVID-19 INFECTIONS IN LUNG TRANSPLANT RECIPIENTS

SESSION TITLE: COVID-19 Infections: Issues During and After Hospitalization SESSION TYPE: Original Investigations PRESENTED ON: 10/17/2022 01:30 pm - 02:30 pm PURPOSE: It has been established that recipients of solid organ transplants have worse outcomes compared to the general population from COVID-19 infections. We sought to determine the course and outcomes of lung transplant recipients (LTR) with COVID-19 infections based on vaccination status and treatments. METHODS: We performed a retrospective study of all LTR from Inova Fairfax Hospital with COVID-19 infections. Infection was confirmed based on symptoms and testing from an urgent care, hospital, or home kit. Patients with presumed but unconfirmed COVID-19 infections were excluded. The study timeframe was the two-year period: 3/1/2020 - 2/28/2022. Data collected included patient demographics, transplant type, immunosuppression, immunization status, episodes of rejection, donor derived cell-free DNA (dd-cfDNA) values (where available), spirometric data, outpatient/inpatient treatments, hospitalization data, and outcomes including death, infections, and other complications. The severity of illness was based on the 8-point ordinal scale. RESULTS: There were 45 LTR who tested positive during the study period;22 male and 23 female, average age of 57 and mean time from transplant of 4 years. 11 of the patients were unvaccinated (UV), 2 partially vaccinated (PV), 11 vaccinated non-boosted (VNB), and 21 vaccinated and boosted (VB). In total, 34 (76%) LTR required hospitalization. Of those hospitalized: 7 UV, 1 PV, 11 VNB, and 15 FV. In addition, 7 of those hospitalized required intubation with only 1/7 surviving to discharge. Overall, 8/45 (17.8%) patients died from COVID-19: 3 UV, 1PV, 1 VNB, 3VB. Infectious complications included 3 cases of PCP, 1 empyema, and 1 reactivation of CMV. For individuals who had spirometry at least 2 weeks after diagnosis (n =25), FVC decreased in 17 LTR by an average of 0.17 L, the FEV1 decreased in 14 LTR by an average of 0.14 L. On repeat spirometry testing (n=14), FVC further decreased in 9 LTR by 0.25 L and the FEV1 further decreased in 7 LTR by 0.13 L. CONCLUSIONS: A large proportion of LTR with COVID-19 infections require hospitalization (76%) with a high associated mortality rate and a sustained lung function decline seen in many who survive. The high mortality was independent of vaccination status, likely reflecting the inability of LTR to mount an immune response. A high index of suspicion and monitoring for superimposed infections, especially PCP, appears prudent. The sustained decline in lung function raises the notion of COVID-19 as a precipitating factor for chronic lung allograft dysfunction (CLAD). CLINICAL IMPLICATIONS: LTR who contract COVID-19 infection represent a high-risk population, even in those fully vaccinated, with potential for hospitalization, death, loss of lung function, and infectious complications. In this population, new algorithms for immunosuppression, monitoring and treatments may help to improve outcomes. DISCLOSURES: No relevant relationships by Shambhu Aryal No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Consulting fee Removed 04/03/2022 by A. Whitney Brown No relevant relationships by Jessica Chun No relevant relationships by Meg Fregoso No relevant relationships by Vikramjit Khangoora Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2021 Added 04/03/2022 by Christopher King, value=Consulting fee Advisory Committee Member relationship with Actelion Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: 2019-2022 Added 04/0 /2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with United Therapeutics Please note: 2020-22 Added 04/03/2022 by Christopher King, value=Consulting fee Consultant relationship with Veracyte Please note: $1001 - $5000 by Steven Nathan, value=Honoraria Removed 03/29/2022 by Steven Nathan Consultant relationship with United Therapeutics Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 by Steven Nathan, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 by Steven Nathan, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 by Steven Nathan, value=Honoraria No relevant relationships by Alan Nyquist No relevant relationships by Michelle Schreffler Speaker/Speaker's Bureau relationship with United Therapeutics Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Consulting fee Speaker/Speaker's Bureau relationship with Bayer Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Speaker/Speaker's Bureau relationship with Janssen&Janssen Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Consultant relationship with Altavant Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Consulting fee Consultant relationship with Acceleron Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria Consultant relationship with United Therapeutics Please note: 2020-2022 Added 04/01/2022 by Oksana Shlobin, value=Honoraria No relevant relationships by Anju Singhal No relevant relationships by Christopher Thomas

INFECTIOUS COMPLICATIONS AFTER TOCILIZUMAB IN PATIENTS WITH COVID: A REAL-WORLD EXPERIENCE

SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread across the world, claiming millions of lives. With the publication of RECOVERY trial and REMAP-CAP trial, tocilizumab is recommended as additional therapy in select COVID populations by various professional societies. Although not observed initially in several randomized trials, concerns regarding serious secondary infections have been raised. Hereby, we seek to describe the epidemiology of infectious complications after tocilizumab in COVID patients admitted to a tertiary community hospital and to determine related risk factors for infections. METHODS: A retrospective cohort study was conducted among COVID patients requiring noninvasive or invasive ventilation who received tocilizumab at our hospital between June 2020 to December 2021. We define infectious complications as positive culture grown on a specimen that was also treated with antibiotics by the primary team. Baseline demographics and laboratory values are obtained through electronic medical records. Continuous outcomes are analyzed with parametric and non-parametric testing. Categorical variables are analyzed using the Chi-Square test. Risk factors are identified through Probit regression analysis and stepwise analysis. Statistics are performed using SPSS and STATA. RESULTS: 52 patients are identified with a median age of 63 and 46.2% female sex. Median hospital admission time since COVID diagnosis is 2 days and median tocilizumab administered time is 6.5 days. Common comorbidities include hypertension (63.5%), hyperlipidemia (50%) and diabetes (44.2%). Infectious complications are documented in 30 patients (57.7%), with 29 episodes of pneumonia, 7 episodes of urinary tract infection, and 4 episodes of bacteremia. Common organisms include MSSA (21%), Pseudomonas aeruginosa (19%), Klebsiella species (13%) and MRSA (5%). There are 9 cases of multidrug-resistant bacterial infection and 3 episodes of invasive fungal infection (1 Candidemia and 2 invasive aspergilloses). 22 patients (43.3%) died in the hospital before discharge with a median alive time after tocilizumab of 16.5 days. Hyperglycemia on admission (defined as a random glucose >200 mg/dl), hypertension and antibiotic use before tocilizumab are independent risk factors associated with infectious complications during regression analysis. Age >65 is the single most significant factor associated with death in the hospital. CONCLUSIONS: In real-world experience, infectious complications are not uncommon in COVID patients who receive tocilizumab. Our analyses show that potential risk factors for developing infections include a history of hypertension, hyperglycemia on admission and antibiotic use before tocilizumab. CLINICAL IMPLICATIONS: More rigorous criteria in patient selection and patient monitoring should be explored in future trials involving tocilizumab in COVID patients. DISCLOSURES: No relevant relationships by Zauraiz Anjum No relevant relationships by Ming-Yan Chow No relevant relationships by Ahmed Elkhapery No relevant relationships by Hafsa Faisal No relevant relationships by Lakshmi G Nair No relevant relationships by Charoo Iyer No relevant relationships by Hongli Liu No relevant relationships by Chengu Niu No relevant relationships by Kaiwen Zhu

COURSE OF CORONAVIRUS INFECTION IN ONCOHEMATOLOGICAL PATIENTS IN THE POSTTRANSPLANT PERIOD

Background: In March 2020, specialists in the field of oncohematology faced the problem of severity of coronavirus infection in patients after high-dose course of chemotherapy and autologous or allogeneic bone marrow transplantation. This required a revision of a number of issues related to the selection of patients for bone marrow transplantation (BMT), the development of new preventive and therapeutic tactics aimed at the treatment of infectious and immunological complications in this category of patients, depending on the nature of the underlying disease, the status of the disease and the timing of the treatment. Aims: To assess the severity, the most typical complications and the COVID 19 severity aspects in patients in early and late post-transplant periods to develop the most optimal tactics for the prevention and treatment of COVID 19 in this group of patients. Methods: An analysis was made of patients after HSCT with active coronavirus infection from 2020 to 2021, hospitalized in the hematology department of the Moscow multidisciplinary hospital (the hospital was completely redesigned to work on the COVID19 profile). A total number of hospitalized patients after HSCT was 25: 4 patients after allogeneic transplantation, 21 -after autologous. According to the timing of HSCT, patients were divided into 2 groups -early post-transplant period (ETP) (2-90 days after HSCT) -14 patients, and late post-transplant period (LTP) (3-24 months) -11 patients. According to nosology, patients were divided into following groups: lymphomas -72%, MM -12%, AA and CML 8% each. All patients were admitted with a positive PCR test (0-7 days of COVID). COVID therapy was carried out according to the protocols adopted in the Russian Federation using antiviral drugs, biological therapy, corticosteroids, anticoagulants. If necessary, the required supportive therapy was carried out for this period of HSCT. Results: Severe COVID19 (CT 3-4 severity) was more often observed in patients in ETP (100%) than in LTP (45%) (p=0.021). The incidence of respiratory failure is 70% and 36% in ETP and LTP, respectively. According to the analysis in ETP, agranulocytosis was observed in 65% of cases, for LTP group -in 18% (p = 0.022). Development of severe infectious complications (bacterial, fungal and viral) was detected in 100% of patients in ETP, in 45% of patients in LTP (p = 0.002). Antifungal therapy was required in 100% of cases in ETP, and only in 27% of the LTP group (p=0.001). 90% of patients in both groups required biological therapy. Mortality in the group of patients in ETP was 35%, while no deaths were registered in the group of patients in LTP (p=0.027). Median of hospitalization period for ETP and LTP patients was 20 and 13 days, respectively. Summary/Conclusion: Patients in the early period after HSCT have a higher risk of developing lower respiratory tract infection, more likely to require antifungals, reserve group antibiotics, and have a greater risk of death from COVID-19. Biological therapy is not contraindicated in case of leukopenia and agranulocytosis in this group of patients.

PROSPECTIVE MULTICENTRIC STUDY ON INFECTIOUS COMPLICATIONS AND CLINICAL OUTCOME IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX

Background: The hypomethylating agents (HMAs) are an important therapeutic option for older patients (pts) with AML and have become the backbone for combination regimens (eg, with Venetoclax). However, there are very limited real-life prospective studies regarding clinical outcome of these pts, including infectious complications and infection related mortality (IRM) during treatment. Aims: To investigate the infectious complications and clinical outcome in AML patients treated with HMAs± Venetoclax (V) outside of clinical trials. Methods: The recruitment of this prospective multicentric study (CE-Id-study:2908) has been completed on December 31, 2020. We enrolled 230 AML pts with a median age of 75 years (range 25-94);157 pts (68%) had >2 relevant comorbidities. Of the 230 cases, 132 (57%) received a first-line therapy with a combination of HMAs+V while 98 (43%) were treated with HMAs monotherapy (azacitidine or decitabine). A total of 1550 cycles of HMAs have been administered (680/1550 with HMAs+V). Results: The best response achieved, with HMAs treatment, was: CR in 44% of cases (57,6% with HMAs+V and 25,5% with HMAs alone, P=0,0001), PR in 17% and SD in 14% of cases (ORR 61%;72% in HMAS+V and 46% in HMAs alone, P=0,0007). The microbiological or radiological proven infectious complications (almost one) occurred in 160/230 (70%) of pts, mainly pneumonia (in 42% of pts) and/or bacteremia/sepsis (one or more events in 29% of pts). Febrile neutropenia (one or more episodes) occurred in 38% of pts and 14 cases of Covid-19 (6%) were reported. After a median follow-up of 9 months (1-24) from the start of HMAs therapy, 144 (63%) pts died and 86 (37%) were alive. The 1 yr OS probability was 46% with a median OS of 10,3 months (11 months in HMAs+V and 9 months in HMAs alone;P=ns). The primary causes of death were: progression of AML (42%), Infection (26%-37/144), Infection+AML (24%), other causes (8%). The IRM was 26% and 19/144 (13%) pts died of infectious complication while in CR/PR (16 in HMAs+V group and only 3 in HMAs group;P=0,005). Data on antibiotic prophylaxis, hospitalization, drugdoses modulation, are available and analyzed in this study. Summary/Conclusion: The results of this real-life, multicentric, prospective study, confirm a higher CR rate in pts treated with HMAs+V compared to HMAs alone (P=0,0001). However, we found a high rate of infectious complications and IRM (26%) with a higher infection related deaths in patients in CR/PR who were treated with HMAs+V (P=0,005). Findings from this study highlight the critical relevance of infection prevention in reducing infectious mortality, which adversely impacts the OS of this frail AML population.

PIVOTING IN A PANDEMIC: THE IMPACT OF COVID-19 ON THE PROVISION OF CARE FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A PRELIMINARY ANALYSIS

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, also known as COVID-19, was declared a worldwide pandemic in March of 2020. Since the onset of the pandemic, the focus of many healthcare systems has shifted toward limiting non-essential visits to hospitals in order to prioritize and allocate resources toward treating those affected by COVID-19, and preventing further exposures. While the effect of COVID-19 has been felt amongst many patient populations, those with inflammatory bowel disease (IBD) have been particularly impacted through delayed appointments and endoscopy, which is critical in disease monitoring. Aims: We aimed to determine how changes to the provision of IBD care due to the COVID-19 pandemic have affected IBD patients. Methods: A retrospective cohort study was conducted using administrative data comparing IBD patients admitted to the gastroenterology ward from March 17 to August 31 2019, with IBD patients admitted from March 17 to August 31 2020 at a tertiary care centre in London, Ontario. Patients were reviewed to assess differences in care utilization and IBD-related outcomes such as hospitalization, surgery and length of stay and in-patient drug therapy. Results: A total of 538 patients (259 in 2019 cohort and 279 in 2020 cohort) were reviewed with 48 and 60 IBD patients meeting the inclusion criteria for 2019 and 2020 respectively. Patient demographics were similar between 2019 and 2020 cohort for age, sex, rurality, disease type, and biologic exposure. A greater proportion of patients were admitted with IBD flares in 2020 (86.7% vs 75%, p=0.03). Furthermore, the 2020 cohort also had a 45% increase in in-patient surgical consultations (p=0.07), a 50% increase in in-patient IBD-related surgeries (p=0.39), a 69% increase in inpatient Remicade prescription (p=0.13) and a 70% increase in infectious complications at presentation to hospital (p=0.21). A shorter median length of stay was reported for patients in the 2020 cohort (4 days IQR 3.95 vs 5.85 IQR 4.65, p=0.09). Conclusions: Preliminary data suggest that during the COVID-19 pandemic, we have seen more deleterious outcomes in our IBD patients such as increased flares necessitating hospital admission. There was also a non-significant trend toward increased infectious complications as well as in-patient surgeries and need for inpatient Remicade. Though these results cannot be fully interpreted due to the need for further sampling, they suggest that IBD patients may be at-risk for poor outcomes in the current climate of medical care. Completion of this study will help define the full impact of care shifts related to reducing the spread of the novel coronavirus on IBD patients and highlight areas of care that need careful assessment and consideration to protect IBD patient health.

The importance of the long Covid-19 in the evolution of patients with neoplasms

Background: Patients with comorbidities especially those with oncological diseases could have severe COVID-19 outcomes. OBJECTIVE: The aim of this study was to evaluate the role of prolonged positivity of SARS-Cov2 in evolution of patients with various neoplasia. Methods: We analysed clinical and laboratory (hematological parameters and inflammatory markers: interleukin-6 and ferritin) data of COVID-19 patients admitted in intensive care unit (ICU) Department of our hospital, during 2020-2021 and presented in medical history solid tumors or haematological neoplasia . The cohort of patients included 78 patients with severe and critical form of COVID-19, 31 patients with solid tumors and 47 patients with hematologic malignancies. We consider long COVID-19 all cases with SARS Cov2 positivity more than 14 days. Results: The frequency of long COVID-19 was quite equal between patients groups with solid tumors and hematologic malignancies, incidence rate 1:2, the incidence rate differences was 1:18, p = 0.75. Long COVID-19 was observed in 60% cases with favourable evolution, Chi-squared 5.35%, p = 0.02, these patients had moderate form and was admitted in hospital in 1 or more days after the onset, median value 3 (min 1, max 55) compared with patients with normal duration of positivity of SARS-Cov2 test-median value 2 (min 1, max 8), p = 0.01. The Kaplan Meyer survival analyses indicated long COVID-19 as predictive factor for unfavourable evolution, Chi-squared 17.97, p < 0.0001. Although we have not obtain significant differences, we observed more severe lymphopenia in patient without long COVID-19, probably because a part of these patients group died in the first 14 days of COVID-19 (0.765 (min 0.04, max 297.64) vs. 1.01 (min 0.09, max 254.35), p = 0.09). The rest of hematological and biochemistry parameters was not significant different between groups. Infectious and thrombotic complication was most frequent in patients with long COVID-19, Chi squared 8.6, p = 0.003. Conclusions: Long Covid-19 is predictable for unfavourable evolution and is associated with sepsis and thrombotic complication. This diagnosis is frequent in patients who was admitted in hospital after the onset of COVID-19 symptoms, early treatment of COVID-19 in oncological patients being very important for favourable evolution.

Infectious issues of therapeutic monoclonal antibodies in multiple sclerosis and neuromyelitis optica spectrum disorders

Various effective monoclonal antibodies (mAbs) have been approved for both multiple sclerosis (MS) and anti-aquaporin-4-seropositive neuromyelitis optica spectrum disorders worldwide, including in Japan. As these newer mAbs have distinct modes of action that effectively suppress the recurrence of inflammation and slow disability progression, they can modulate and interfere with the protective immune response against pathogens, resulting in various infectious complications. Among various mAbs, natalizumab (NTZ) has the highest risk of causing progressive multifocal leukoencephalopathy (PML), a rare but fatal opportunistic brain infection caused by John Cunningham polyomavirus. Switching from NTZ to B-cell-depleting mAbs, such as ocrelizumab, is also a possible risk factor for PML development. Alemtuzumab carries the risk of reactivation of varicella-zoster virus (VZV);therefore, prophylactic acyclovir treatment is required. NTZ has also been associated with VZV reactivation. Eculizumab can cause severe meningococcal infection due to Neisseria meningitis, and vaccination prior to treatment induction is required. Attention to the reactivation of hepatitis B or Mycobacterium tuberculosis is also needed during mAb therapy. Additionally, in the era of severe acute respiratory syndrome coronavirus 2 infection (COVID-19), the risk for of developing severe COVID-19 may be associated with some mAbs, such as B-cell-depleting agents. Thorough understanding and mitigation strategies for infectious risks are essential.

Incidence of Early Revaccination After Pediatric Allogeneic Hematopoietic Stem Cell Transplant

Background: Infections are a common cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Prolonged immune recovery post-HSCT increases the risk of infection and raises concern for poor response to vaccinations. Reimmunization is recommended for all pediatric HSCT patients by transplant and infectious disease organizations1,2, and individual institutions often develop revaccination guidelines. Objective: At Vanderbilt Children's Hospital (VCH), the clinical practice guideline (CPG) instituted in June 2015 recommends early initiation (6 months) of reimmunization in immunologically appropriate patients, starting with Haemophilus influenzae type B (Hib) and pneumococcal conjugate (PCV13) vaccinations. Therefore, we examined the feasibility of early vaccination for allogeneic HSCT patients and determined the causes of delayed or lack of vaccination. Methods:A retrospective chart review of the electronic medical record was conducted under an IRB-approved protocol. Data was gathered and entered in a REDCap database, including dates of vaccination, immune reconstitution studies (IgG concentration, T/B cell subsets) and clinical outcomes [e.g., intravenous immunoglobulin (IVIg) administration, graft versus host disease (GvHD), relapse] through 6-month (+/- 30 days) post-HSCT. Early revaccination was defined as Hib and PCV13 administration within 210 days post-HSCT. Patients not meeting this definition were further examined for factors that led to delay or lack of vaccinations. Patients were included if they were alive without underlying disease progression or graft failure 6-months post-HSCT. Results: Between June 15, 2015 and June 30, 2021, 66 patients met inclusion criteria. Early revaccination occurred in 21/66 patients (32%). Of the 45/66 (68%) that did not receive 6-month vaccinations, the most common reason was concern for impaired immune reconsti- tution (n = 33/45, 73%). Indicators of poor immune recovery included recent IVIg administration (n = 15), ongoing immunosuppression (n = 24), and poor B cell recovery (n = 4);many patients had multiple indications. Other reasons for delay included patient or parent refusal (n = 4), prioritization of COVID vaccinations (n = 3), scheduling conflicts (n = 4), and other (n = 1). Conclusions: Early vaccination occurred in 32% of patients. At 6 months post-HSCT, 50% of patients had poor immune reconstitution resulting in appropriate vaccination delays. However, scheduling conflicts and vaccine hesitancy despite eligibility were small but significant contributors, accounting for 17% of delays. This is a small, single center study but highlights significant challenges with delivery of best practice guidelines. Future directions could include engagement with other institutions regarding best practices to address vaccine hesitancy and to further explore if early revaccination reduces risk of infectious complications post-HSCT.

Vaccination of cancer patients

Cancer patients have an increased risk of infectious complications, the main cause of which is an immunodeficiency condition caused by the cancer itself and its therapy. Therefore, it is appropriate to protect patients by vaccination, in particular vaccination against influenza, pneumococcal infections and covid-19. Appropriately chosen vaccines and the right timing of their administration can as a part of supportive care contribute to the success of cancer therapy.

Risk of infections with BCMA-directed immunotherapy in multiple myeloma

Introduction: B cell maturation antigen (BCMA) is a novel target for T cell immunotherapy in MM including bispecific antibody (bsAb) and chimeric antigen receptor therapy (CAR-T). BCMA is critical for survival of the long-lived plasma cell, responsible for generation of protective antibodies. Impaired immune reconstitution, cytopenias, B cell aplasia and hypogammaglobinemia can compound preexisting MM-induced immunosuppression. In the case of bsAb, potential redirection/activation of T regulatory cells can create an immunosuppressive milieu. Herein, we describe the clinically relevant infectious complications observed across different BCMA-directed therapies used across multiple clinical trials at our center. Methods: Infections confirmed by microbiologic or histopathologic evidence were captured from the D1 C1 of bsAb and D 1 of lymphodepleting chemotherapy of autologous BCMA CAR-T therapies. The NCI CTCAE v5 was used to describe the site and grade of infections. Hypogammaglobinemia and severe hypogammaglobinemia were defined as ≤700 mg/dl and ≤400 mg /dl, respectively. Standard antimicrobial prophylaxis included herpes zoster prophylaxis for all MM patients with antibacterial (levofloxacin) / antifungal (fluconazole) during periods of neutropenia and IVIG supplementation as per the treating physician's discretion. PCP prophylaxis was prescribed to CAR T recipient per institutional guidelines. Descriptive statistics and comparisons were performed using two-sample t-test for continuous variables and chi-square goodness of fit test for categorical variables. Results: We identified 62 patients who received BCMA-directed bsAb (n=36) or CAR-T (n=26) between 2019-2021(table 1). The median age was 66 (range 48-84) years with % females and 14.8% of patients belonging to Black race. The median time to bsAb and CAR-T use from diagnosis were 6.6 (range 0.83-15.5) and 2.6 (range 0.35-14.4) years, respectively. The median lines of prior therapy were 6 (range 1-11) with BCMA CAR-T recipients receiving fewer prior lines of therapy (4 vs 6, p=<0.001). The baseline lymphocyte count was higher in the CAR-T (14.71 vs 0.84;p=<0.001). Baseline severe hypogammaglobulinemia and lymphopenia were present in 30% and 26.7% of all patients, respectively. Tocilizumab was used in 40.9% (bsAb -30.8% versus CAR-T 55.6%) patients for CRS. IVIG was used in 25% of patients. The median study duration for bsAb was 4 (range 0.03- 24) months across multiple dose levels. Median follow up among CAR-T recipients was 3.9 (range 0.3 - 22.3) months. Among recipients of bsAb, 41.2% of patients experienced at least one episode of infection vs. 23.1% with CAR-T (p=0.141). The cumulative incidence of infection with bsAb and CAR-T were 22 and 8, respectively. The spectrum of infections with bsAb was predominantly bacterial (64.3% While gram negative infection (Escherichia coli and Klebsiella pneumoniae bacteremia, Proteus mirabilus and Psuedomonas aeroginosa urinary tract infections) were seen in 6 patients, skin infection including cellulitis occurred in 4 patients, with 1 case of necrotizing cellulitis. Bacteremia with rare opportunistic pathogens - Rhizobium radiobacter and recurrent Ochrobacterium anthropi were also observed . Viral infections included rhinovirus, cytomegalovirus, and parvovirus B19 reactivation, and COVID-19. About 50% of infections were ≥ grade 3 with 2 grade 5 events (Pseudomonas aeruginosa bacteremia and COVID-19). In the CAR-T group, we observed more viral infections (66.7% vs 35.7%;p=0.028) and fewer bacterial infections (33.3% vs 64.3%;p=0.028) . Common viral infections included rhinovirus, RSV, and herpes simplex virus reactivation. In this group 25% of infections were ≥grade 3. Conclusion: BCMA-targeted therapies seem to be associated with clinically significant bacterial and viral infections. Repetitive dosing with bsAb therapies could be the reason for the propensity to serious bacterial infections compared to CAR-T recipients and may need novel prophylaxis strategies. (Figure Presented).

PREGNANCY, VALVULAR DISEASE, AND ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS): A COLLABORATIVE APPROACH TO OUTCOMPETING COMPETING HEMODYNAMIC DEMANDS

Background: A 35-year-old G1P1 woman with a history of bioprosthetic mitral valve (MVR) and aortic valve (AVR) replacements and a tricuspid valve annuloplasty for presumed rheumatic heart disease who presented at 35 weeks gestational age with COVID-19 ARDS and shock. Case: The patient arrived with ARDS requiring intubation and distributive shock. Transthoracic echocardiogram (TTE) revealed a small left ventricular (LV) cavity with LV hypertrophy, MVR with mean gradient of 14 mmHg, and a mid-peaking transaortic gradient of 96 mmHg consistent with fixed obstruction. This gradient was likely due to LV outflow tract obstruction (LVOTO) from the combination of a small LV cavity and septal angulation of the MVR struts rather than AVR dysfunction. The patient underwent emergent cesarean section. Decision-making: The maternal and fetal risks of ARDS and distributive shock were primary considerations in undergoing cesarean section. Decisions regarding management thereafter were driven by three elements of her clinical presentation - anticipated peripartum hemodynamic shifts, multivalvular disease, and ARDS. The increased plasma volume from postpartum autotransfusion risked worsening her ARDS but also potentially benefited the LVOTO through increased preload. The effect of lower postpartum cardiac output and heart rate on valvular obstruction in series also had to be considered. To balance these hemodynamic demands, after delivery, her vasopressors were switched from norepinephrine to phenylephrine, and she was judiciously diuresed. A postpartum TTE demonstrated improved transmitral gradients (mean 5 mmHg) but ongoing LVOTO. Higher filling pressures than otherwise ideal in ARDS were tolerated given persistent gradients. She was liberated from hemodynamic and ventilator support and transferred out of ICU care. Though she died of infectious complications weeks later, close collaboration between the critical care, obstetrical, and cardiovascular teams were essential to her care. Conclusion: Care of the peripartum patient with cardiovascular disease, especially valvular disease, must take into consideration both their cardiac pathology and expected peripartum hemodynamic shifts.