Rare Presentation of Coxsackie Virus B Myopericarditis as Atypical Pneumonia and Sepsis

INTRODUCTION: While myopericarditis due to Coxsackie virus-B has been widely reported, multi-organ involvement is rare. We report a unique case of Coxsackie B myopericarditis, which presented with rash, atypical pneumonia, hepatitis, and sepsis. DESCRIPTION: A previously healthy 32-year-old man presented to the emergency department in January 2022 endorsing shortness of breath, high-grade fever (39.2degreeC), non-pruritic rash on extremities, vomiting, and diarrhea. He had tachypnea (24/min), hypoxia (SpO2 93% on air), and mild lymphadenopathy in the neck. Initial evaluation was pertinent for leukocytosis (17.8 thousand/muL) with neutrophil predominance (89.4%), elevated inflammatory markers (D-dimer [4390 ng/mL], procalcitonin [1.79 ng/ mL], CRP [180.7 mg/L], lactate [3.19 mmol/L]), and transamnitis (AST: 160 U/L, ALT: 116 U/L);SARS-CoV-2 and blood cultures were negative. Chest imaging showed bibasilar consolidation, perihilar ground-glass nodules, and pericardial effusion;ultrasound showed acute hepatitis. He was empirically started on ceftriaxone and azithromycin. However, absence of clinical improvement, persistence of high-grade fever, and leukocytosis with low absolute CD3, CD4, and CD8 counts (286 cells/UL, 199 cells/UL and 71 cells/UL, respectively) suggested atypical infection;vancomycin and doxycycline were added. Further infection and autoimmune workup was negative. He developed atrial fibrillation and an echocardiogram was remarkable for ejection fraction of 50-55%, moderate pericardial effusion circumferential to the heart, and minimal collapse of the right atrium. On subsequent testing, Coxsackie virus B type 3 IgM was positive (1:320, reference 1:10). All antibiotics were discontinued, and the patient was managed with diltiazem, colchicine, ibuprofen, and supportive care;anticoagulation was not initiated. After a remarkable improvement in symptoms and rash, he was discharged home. Follow-up imaging showed resolution of bibasilar consolidations and pericardial effusion. DISCUSSION: The likely mechanism of Coxsackie virus B-induced damage to myocytes (and possibly multiorgan involvement) is immune-mediated and direct viral cytotoxicity. Our patient's atypical pneumonia responded well to colchicine and ibuprofen. A high index of suspicion is warranted.

PROLONGED COLONIZATION AND COISOLATION OF SARS-COV-2 IN UNVACCINATED RECIPIENTS OF LUNG TRANSPLANTS

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: We describe two unvaccinated lung transplant recipients (LTRs) with mild COVID-19 and prolonged SARS-CoV-2 colonization who presented with recrudescence of symptoms due to superinfection. CASE PRESENTATION: Case 1: A 57-year-old LTR (August 2018) presented to the emergency room (ER) in July 2020 with headache, positive SARS-CoV-2 nasopharyngeal swab-PCR result, and elevated D-Dimer. He recovered at home and tested negative for SARS-CoV-2 on day 28. He presented to the ER again in October 2020 with chest pain. At this time, evaluation revealed a positive SARS-CoV-2 nasopharyngeal swab-PCR result, positive SARS-CoV-2 IgG (index 3.41), leukocytosis, and elevated inflammatory markers. Of note, nasopharyngeal swab was also positive for rhinovirus. Imaging showed new mild bibasilar ground-glass opacities. Patient was treated with remdesevir, convalescent plasma, and pulse corticosteroid. His SARS-CoV-2 PCR test was negative on day 3 of the remdesevir regimen;he remains clear of SARS-CoV-2 and rhinovirus to date, with complete clinical and radiologic recovery (Figure 1, Case 1). His immunosuppression was unchanged. Case 2: A 75-year-old LTR (July 2016) with pancytopenia presented for a sick visit in May 2020 with cough and fever. His SARS-CoV-2 nasal wash-PCR test was positive;imaging was unremarkable. He was sent home on pulse corticosteroid and levofloxacin. A week later in June 2020, he presented to the ER with worsening cough. At this time, evaluation revealed positive SARS-CoV-2 IgG (index 7.58), leucopenia, thrombocytopenia, elevated inflammatory markers, and new radiographic bibasilar ground-glass opacities (Figure 1, Case 2). His condition improved with intravenous antibiotics and corticosteroids. He consistently tested positive for SARS-CoV-2 in nasal wash samples for 3 months, with the first negative test in September 2020. He was hospitalized in January 2021 for neutropenic fever, P. Aeruginosa (PsA) infection in bronchoalveolar lavage (BAL), and anti-PsA antibodies in the serum. At this time, he also had SARS-CoV-2 colonization in BAL despite negative PCR results of nasal wash samples. His condition improved with 14 days of antibiotics. He was stable at his last follow-up. DISCUSSION: Both patients had an initial episode of mild COVID-19 pneumonitis, appropriate seroconversion, and prolonged viral colonization in the respiratory tract. Immunosuppression may have predisposed to rhinovirus and PsA superinfection in case 1 and 2, respectively. CONCLUSIONS: A high index of suspicion for superimposed infections in LTRs recovering from COVID-19 is warranted. Reference #1: 1. Hogan JI, Kotton CN. A Call for Caution in the Immunocompromised: Coronavirus Disease 2019 Associated With Mortality in a Vaccinated Lung Transplant Recipient. Open Forum Infect Dis. 2021 Nov 10;8(12):ofab557. DISCLOSURES: No relevant relationships by Hesham Abdelrazek No relevant relationships by Ashwini Arjuna No relevant relationships by Bhuvin Buddhdev No relevant relationships by Deepika Razia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia

Persistent Subclinical SARS-CoV-2 Isolation After Redo Lung Transplant for COVID-19-Induced Lung Injury

Introduction Lung transplantation (LTx) is lifesaving for patients with irreversible lung injury due to COVID-19;however, all viable virus must be cleared before transplant. Prolonged viral shedding is common, particularly among immunosuppressed patients. Thus, ongoing detection of SARS-CoV-2 RNA may delay transplant and prolong hospitalization. We report a case of an LTx recipient who developed COVID-19-associated lung injury with prolonged viral shedding that persisted following redo LTx. Case Report A 48-year-old man developed COVID-19 17 months after bilateral LTx. His illness rapidly progressed to hypoxemic respiratory failure requiring bilevel ventilation and prone positioning. He was treated with corticosteroids, remdesevir, convalescent plasma, anticoagulation, and reduced immunosuppression. Tocilizumab was not administered as data supporting its use was unavailable. Despite aggressive therapy, he remained hypoxemic and developed radiographic evidence of pulmonary fibrosis. SARS-CoV-2 was persistently isolated between November 2020 and April 2021;the PCR cycle threshold in March 2021 was 32, indicating a low level of viral RNA. There was no evidence of antibodies to SARS-CoV-2. Finally, after 2 negative nasopharyngeal swabs in April, he underwent redo bilateral LTx in May 2021, 163 days after his initial diagnosis. Postoperative critical illness myopathy required prolonged mechanical ventilation, nutrition via a feeding tube, and 19 days at an acute rehabilitation center. Routine surveillance bronchoscopy 40 days after retransplant revealed SARS-CoV-2 in bronchoalveolar lavage fluid and again in a nasal wash sample. He had no COVID-19 symptoms at the time of viral isolation, and inflammatory markers were normal. He was empirically treated with casirivimab and imdevimab, with resolution of SARS-CoV-2 isolation 8 days later. Summary Prolonged viral shedding is common in immunocompromised patients with COVID-19;however, ongoing viral isolation is not a reliable indicator of active viral replication and transmissibility. Our patient had persistent SARS-CoV-2 isolation after redo LTx with no evidence of COVID-19 or allograft injury. Thus, persistent viral shedding alone may not be an absolute contraindication to LTx and additional factors such as PCR cycle threshold and time from original infection should be considered.

Lung Transplantation for COVID-19-Induced Respiratory Failure: Single-Center Case Series

Purpose Prior to the COVID-19 (C19) pandemic, adult respiratory distress syndrome (ARDS) was an unusual indication for lung transplant (LT);thus, short- and long-term outcomes data are lacking. As the pandemic continues, there is an increased need for post-LT data. Thus, we report our single-center experience transplanting 11 patients for C19 ARDS. Methods We conducted a chart review of LT recipients (LTRs) transplanted for C19 ARDS between 8/1/21 and 7/31/21. Descriptive statistics were used. Results Most LTRs were male (82%, n=9). The median age at LT, body mass index, and lung allocation score were 47 (43, 54) years, 28.9 (26, 30) kg/m2, and 84.5 (60, 88), respectively. The median interval from initial hospitalization to listing and listing to LT was 119 (97, 124) and 5 (4, 11) days, respectively. Pretransplant COVID-related morbidities included venous thromboembolism (55%, n=6), hemorrhage requiring transfusion (36%, n=4), pneumothorax (55%, n=6), bacterial pneumonia (82%, n=9), bacteremia (45%, n=5), fungemia (36%, n=4), renal failure requiring renal replacement therapy (RRT;9%, n=1), cerebrovascular event (9%, n=1), and musculoskeletal weakness (100%, n=11). Most patients required mechanical ventilation (91%, n=10), and 55% (n=6) were intubated at the time of LT. Furthermore, most patients required ECMO support (73%, n=8) and 36% (n=4) were on ECMO at the time of LT. Intraoperatively, 64% (n=7) of patients required cardiopulmonary bypass, 73% (n=8) had severe intrathoracic adhesions, 73% (n=8) had delayed chest closure, and 18% (n=2) had an unexpected return to the operating room. Prevalence of primary graft dysfunction grade 2 or 3 at 72 hours was high (91%, n=10), median duration of mechanical ventilation after LT was 10 (6, 19) days, but no one required ECMO rescue. To date, 10 (91%) LTRs have been discharged, and 2 (20%) have been readmitted within 30 days;the median post-LT hospital stay was 18 (14, 24) days;all discharged LTRs required acute rehabilitation for a median of 17.5 (14, 23) days. Ten LTRs (91%) at a median of 208 (167, 245) days post-LT;1 LTR died 344 days post-LT of treatment-refractory allograft failure due to aspiration and antibody-mediated rejection. Conclusion Despite pre-LT critical illness, intraoperative challenges, and prolonged post-LT recovery, LT appears feasible for carefully selected patients with irreversible C19 ARDS.

Outcomes of Critically Ill Lung Transplant Recipients with COVID-19

Critically ill patients with COVID-19 are at high risk of morbidity and mortality. This risk may be even higher among lung transplant recipients (LTxRs) as they are immunosuppressed and typically older with multiple co-morbidities. The aim of this study was to characterize the outcomes of critically ill LTxRs with COVID-19. LTxRs with COVID-19 hospitalized in the ICU between 06/01/2020 and 02/28/2021 were included and classified as alive or deceased. Baseline clinical characteristics, laboratory results, and complications were reviewed. Death due to COVID-19 was the primary outcome. Descriptive statistics were used. Twenty-five LTxRs (13 men;8 alive, 17 deceased) were included. Median (IQR) age, interval between LTx and COVID-19 diagnosis, and duration of ICU stay was 66 years (56, 71), 27 months (10, 51), and 19 days (10, 28), respectively. Pre-existing diabetes and chronic kidney disease were common (68%, 68%). Although statistical significance was not reached due to small sample size, survivors trended toward lower levels of CRP, ferritin, and D-Dimer at ICU admission. Fewer survivors had a stroke (0% vs 6%), hemorrhage requiring transfusion (14% vs 18%), new-onset heart failure (14% vs 29%), venous thromboemboli (24% vs 33%), and renal failure requiring dialysis (25% vs 53%). At a median of 8 days after COVID-19 diagnosis, 18 (72%) LTxRs required intubation. The need for mechanical ventilation increased the risk of death 4.327-fold (p=0.054) and lowered the probability of 60-day survival (16.7% vs 71.4%, p=0.035;Figure 1). The median survival of deceased subjects was 23 days (17, 34). Most LTxRs received corticosteroids, convalescent plasma, remdesevir, and reduced immunosuppression. Among LTxRs that survived to hospital discharge, 38% (3) were discharged home, 50% (4) required acute rehabilitation, and 75% (6) were supplemental oxygen dependent. Critically ill LTxRs with COVID-19 have high morbidity and mortality. The need for mechanical ventilation portends a poor prognosis. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Obese Lung Recipients May Be Susceptible to Severe COVID-19 Outcomes Compared to Controls

Obesity is thought to increase COVID-19 (C19) related morbidity and mortality in nontransplant patients;however, the data in lung transplant literature are lacking. We aimed to study impact of body mass index (BMI) on outcomes of lung transplant recipients (LTR) with C19. From March 2020 to August 2021, 91 lung recipients with C19 were included and classified as controls (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) at the time of LT listing. Primary outcome was death. Secondary outcome was C19-related medical morbidity. Cox proportional hazard analysis and Kaplan-Meier method were used. Controls (69%, n=63) and obese (31%, n=28) subjects were comparable in terms of baseline characteristics before C19 onset. Compared to controls, obese subjects tended to have more severe inflammation and a higher prevalence of hypoxemia, requirement of ICU, mechanical ventilation, and death (Table 1). Also compared to controls, the risk of death tended to be higher and probability of survival tended to be lower in obese subjects (HR: 1.971 [0.956-4.065], p=0.066 and 73% vs 53.6%, p=0.061, respectively;Figure 1). However, coinfections and post-C19 allograft function were comparable between the two groups (Table 1). Of note, mycophenolate was stopped or reduced upon/during hospitalization in both groups alike. In our study, obese LTRs trended toward an increased risk of death from C19 compared to controls. This is the first data on the impact of obesity on C19 in LTRs. The role of leptin as a pro-inflammatory substance can be speculated. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 Has a High Mortality Rate in Lung Transplant Recipients: A Large Single-Center Experience

Immunosuppressed patients, particularly solid organ transplant recipients, are at an increased risk of death from COVID-19. We report a large single-center experience with COVID-19 in lung transplant recipients (LTRs). This is a retrospective cohort study of 91 LTRs diagnosed with COVID-19 between March 1, 2020 and August 31, 2021. Patients were classified as alive (n=61) or deceased (n=30). The Kruskal-Wallis and Chi-squared tests were used for data analysis. Mortality from COVID-19 was high (n=30, 33%). There was no difference in baseline clinical characteristics between alive and deceased patients;age, medical co-morbidities, body mass index, and lung function were similar (Table 1). The vast majority of patients were hospitalized (n=79, 86%), not only for severe illness but also to receive remdesivir, an infusion available only to inpatients. Patients that died were more commonly hypoxemic and admitted to the ICU, more likely to require mechanical ventilation, and had a longer hospital stay. Of the 24 intubated patients, only 4 survived (16.7%);2 patients were placed on ECMO and both died. Deceased patients had higher peak levels of D-dimer, ferritin, procalcitonin, and lactate dehydrogenase. The vast majority of patients received corticosteroids;deceased patients were more likely to be treated with remdesivir and tocilizumab. Extrapulmonary complications were more common in deceased patients: 33% developed renal failure requiring hemodialysis and 19.2% developed multi-organ system dysfunction. The median time to death was 1.1 (0.63, 3.70) months;3 patients survived the acute illness but died several months later of complications from post-adult respiratory distress syndrome-fibrosis. The COVID-19 pandemic has had catastrophic consequences for lung transplant recipients. We hope that high vaccination rates, reduction of immunosuppression in the early disease period, and more effective antiviral therapies can reduce mortality. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A Comparison of Short-Term Morbidity and Mortality Among Inpatient Lung Transplant Recipients Transplanted for COVID-19 and Other Restrictive Lung Diseases

Patients with respiratory failure (RF) who are hospitalized at the time of lung transplant (LTx) have higher post-LTx morbidity and mortality than those who are well enough to remain at home. Complications may be even worse in patients transplanted for COVID-19 (C19), as they are commonly critically ill having endured prolonged mechanical ventilation, ECMO support, myopathy, malnutrition, and superimposed infections. In a retrospective cohort study, we compared inpatient lung transplant recipients (LTxRs) transplanted for C19 vs. other underlying restrictive lung diseases (RLDs) After IRB approval, patients who underwent inpatient LTx between 1/1/2014 and 8/31/2021 were categorized by indication: C19 or RLD. We excluded LTxRs <18 years old, a primary indication for LTx other than UNOS disease group D, and redo LTx. Primary outcomes were postoperative morbidity and 90-day survival. Out of 163 inpatient LTxRs, 141 met inclusion criteria: 11 (7.8%) with C19 and 130 (92.2%) with RLD. LTxRs with C19 were younger, had a longer pre-LTx hospital stay, and more likely needed pre-LTx mechanical ventilation and ECMO support. LTxRs with C19 were also more likely to have severe adhesions intraoperatively and their chest was more commonly left open after LTx due to a perceived risk of ongoing bleeding. In addition, LTxRs with C19 had a higher prevalence of PGD3 at 72 hours and longer post-LTx hospital stays and trended toward longer post-LTx mechanical ventilation and need for inpatient rehabilitation. The 2 groups had similar 90-day survival (C19, 100% vs. RLD, 95.4%, p=0.472), however, LTxRs with C19 had a higher incidence of acute cellular rejection and DSA production (>2,000 MFI) within 6 months of transplant. LTxRs with C19 are typically sicker and have more post-LTx complications than LTxRs with RLD hospitalized at the time of LTx. However, 90-day survival is comparable and high in both groups. Long-term follow-up is needed. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

EXCELLENT ALLOGRAFT RECOVERY DESPITE PROLONGED SARS-COV-2 SHEDDING AFTER REDUCTION OF IMMUNOSUPPRESSION IN LUNG TRANSPLANT RECIPIENT

TOPIC: Transplantation TYPE: Medical Student/Resident Case Reports INTRODUCTION: Immunosuppressed lung transplant recipients (LTxRs) are predisposed to severe SARS-CoV-2 disease, impaired virus clearance, and increased mortality. Successful recovery from SARS-CoV-2 infection after reduction of immunosuppression (IS) has been reported in kidney and heart transplant recipients [1,2]. We report a case of favorable allograft outcome after reduction of IS in an LTxR with SARS-CoV-2 pneumonia despite prolonged virus shedding. CASE PRESENTATION: A 58-year-old bilateral LTx recipient (July 2020) with blood type A+ was admitted for a positive SARS-CoV-2 RT-PCR result from a nasal wash on July 31, 2020 (day 1). He exhibited fever, increasing shortness of breath, a productive cough, and bilateral radiographic infiltrates, but normal oxygen saturation on room air and stable pulmonary function tests (FVC and FEV1 at 3.17 and 2.65 liters, respectively). Shortly after hospitalization, his dyspnea and oxygen requirement increased (3 LPM) and inflammatory markers were elevated (nadirs of lymphocyte 2.7 thousand/µL and platelet 158 thousand/µL;peaks of D-dimer 260 ng/mL, CRP 75.2 mg/L, ferritin 219 ng/mL, pro-calcitonin 0.22 ng/mL, and LDH 215 U/L). Imaging favored progression of SARS-CoV-2 pneumonia. DSA against DP1 measured 1350 MFI, and immunoglobulin therapy was started. The patient was managed with intravenous corticosteroid pulse, Remdesivir, and convalescent plasma along with appropriate antibiotic therapy due to additional concern for superimposed infection. On day 8 of illness onset, the patient no longer had clinical symptoms, and he was discharged on room air and steroid taper. On outpatient follow-up, the patients' endurance had increased;PFTs improved (FVC and FEV1 at 3.9 and 3.39 L, respectively);DSAs were reassuring;and radiographic changes had resolved by day 42 (Figure 1: serial chest imaging from illness onset to day 42). Of note, the ImmuKnow result at illness onset was 64 ng/mL, and mycophenolate (MMF) was reduced to 500 mg BID, after which the ImmuKnow result increased to 560 ng/mL. Seroconversion for SARS-CoV-2 IgG was mounted on day 26 (index 1.56), and MMF was resumed to baseline dose of 750 mg BID on day 35. Remarkably, prolonged viral shedding in nasal wash was noted with the first negative RT-PCR for SARS-CoV-2 on day 47. DISCUSSION: Our patient had excellent recovery with intact graft function despite prolonged virus persistence. Although an immunosuppressed state may have predisposed our patient to bacterial superinfection, reduction of MMF possibly augmented the antiviral response. Despite reduced IS, seroconversion and virus clearance may have been impacted. CONCLUSIONS: Immunosuppressed LTxRs with SARS-CoV-2 pneumonia may demonstrate prolonged viral shedding. Reduction in IS may facilitate allograft recovery despite delayed PCR conversion. Isolation measures should be considered due to possible prolonged infectivity. REFERENCE #1: Li F, Cai J, Dong N. First cases of COVID-19 in heart transplantation from China. J Heart Lung Transplant. 2020 May;39(5):496-497. REFERENCE #2: Zhu L, Xu X, Ma K, Yang J, Guan H, Chen S, Chen Z, Chen G. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant. 2020 Jul;20(7):1859-1863. DISCLOSURES: No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by Ross Bremner, source=Admin input No relevant relationships by Ericka Charley, source=Web Response No relevant relationships by Hesham Mohamed, source=Web Response No relevant relationships by Kristine Nally, source=Web Response No relevant relationships by Ashraf Omar, source=Admin input No relevant relationships by Deepika Razia, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=H noraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 by Rajat Walia, source=Web Response, value=Honoraria