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 Viral Detection After Resolution of COVID-19 in Lung Transplant Recipients

Introduction Persistent detection of SARS-CoV-2 viral particles has been seen in the absence of symptoms in other solid organ transplant recipients. We report this unique phenomenon in lung transplant (LTx) recipients. Case Report We present the following cases of prolonged viral shedding in 3 LTx recipients: Patient A - 68-year-old female, bilateral LTx recipient for COPD (02/2020), Patient B - 65-year-old male, bilateral LTx recipient for IPF (07/2020), and Patient C - 64-year-old female, bilateral LTx recipient for COPD (08/2020). There were no major intraoperative complications, and the maintenance immunosuppression regimen was the same across patients. Patient A contracted COVID-19 at our center 10 months after transplant, reporting upper respiratory infection symptoms, after initially presenting with persistent headaches and diagnosed with posterior reversible encephalopathy syndrome. Patients B and C presented to clinic with myalgias and mild dyspnea at one and five months after transplant, respectively. SARS-CoV-2 was detected by RT-PCR of nasopharyngeal specimens in all patients. Chest CT demonstrated typical findings of COVID-19 pneumonia in all patients. Patients A and C received remdesivir and belatacept and were discharged home on days 5 and 7, respectively;Patient B received remdesivir and convalescent plasma and was discharged home on day 8. All were in stable clinical condition on room air. All 3 patients had persistently positive nasopharyngeal swab samples up to four weeks after hospitalization, despite absence of symptoms. We did not augment immunosuppression in these patients. Imaging findings during and after the infectious course are shown in Figure 1. Patient C has persistent lower lobe radiographic changes after COVID-19. Summary LTx recipients may exhibit prolonged viral shedding up to at least 1 month despite resolution of symptoms. Well-established cohort studies are needed to elucidate the full duration of viral shedding in this group.

Methylene blue and hydroxocobalamin in a severely vasoplegic lung transplant recipient

INTRODUCTION: Vasoplegia is defined as a refractory shock state with profound hypotension in the setting of reduced systemic vascular resistance and high cardiac output. Lung transplantation is an arduous surgery often requiring cardiopulmonary bypass, which ultimately predisposes to vasoplegia. We detail the treatment of a patient with end-stage lung disease secondary to COVID-19 pneumonia undergoing lung transplant who developed vasoplegia. DESCRIPTION: The patient is a 36-year-old female who was admitted with profound hypoxemic respiratory failure secondary to COVID-19 pneumonia. Despite initial therapy, she remained ventilator-dependent with need for extracorporeal membrane oxygenation (ECMO) support. Given her single organ failure status - lungs being solely affected - she was promptly considered for lung transplant evaluation upon resolution of her active SARS-CoV-2 infection. She was ultimately deemed appropriate for listing and underwent subsequent transplant. The surgery required the use of cardiopulmonary bypass, given the extensive adhesions of the native COVID-19-infected lungs. The lungs were, unfortunately, quite necrotic, with multiple purulent pockets. She was profoundly hypotensive throughout the surgery and required massive fluid resuscitation, as well as multiple vasopressors. In the setting of this vasoplegia, she received multiple doses of methylene blue at 2 mg/kg, with only marginal improvement in blood pressure. Decision was made to add high-dose (5 g) hydroxocobalamin in an attempt to synergistically stabilize blood pressure. Intraoperatively, her blood pressure stabilized within hours;she remained on ECMO support and was transferred to the ICU postoperatively. Eventually, she was slowly weaned from her vasopressors, with stable blood pressure. DISCUSSION: Methylene blue mechanistically inhibits inducible nitric oxide synthase and guanylyl cyclase, while hydroxycobalamin acts as a nitric oxide scavenger. Both agents have been used independently to treat vasoplegia during cardiopulmonary bypass. Together, they may be used as a salvage therapy to improve blood pressure in refractory cases of shock seemingly exacerbated by the cytokine milieu promoted by recent SARS-CoV-2 infection.

A CASE OF ERDHEIM-CHESTER DISEASE IDENTIFIED SIX MONTHS AFTER LUNG TRANSPLANT

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Erdheim-Chester disease is a rare type of non-Langerhans histiocytosis that can manifest with bone pain, marked elevation of alkaline phosphatase, and osteosclerotic lesions of long bones. CASE PRESENTATION: A 37-year-old female, bilateral lung transplant recipient (10/2020) with a history of post-COVID-19 acute respiratory distress syndrome, complicated by acute cellular rejection, antibody-mediated rejection, and refractory gastroparesis, was found to have Erdheim-Chester disease in the work-up of infiltrative pattern of liver enzymes at 6-months after transplant. DISCUSSION: The early postoperative course was complicated as described above;during her most recent hospital admission, she had an isolated elevation of alkaline phosphatase (208 U/L) with no obvious gastrointestinal symptoms, excluding gastroesophageal reflux or other hepatobiliary pathology. Over the course of one week, her alkaline phosphatase increased to 928 U/L, and the patient described a new onset, mild and non-specific lower tibial pain. A gamma-glutamyl transferase was elevated, necessitating a skeletal work-up. A bone scan and lower extremity radiographs both showed subtle, patchy, intramedullary sclerosis and cortical thickening in the right lower extremity. Together, her bone pain, elevated alkaline phosphatase, and radiologic features were consistent with Erdheim-Chester disease. Although a bone biopsy was warranted, given her guarded prognosis, this intervention was not pursued. CONCLUSIONS: Erdheim-Chester disease generally requires careful observation for disease progression. Unfortunately, in a lung transplant recipient with worsening allograft function and repeated hospitalization, the prognosis is poor. DISCLOSURE: Nothing to declare. KEYWORD: Erdheim-Chester Disease

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

POSSIBLE ZOONOTIC TRANSMISSION OF UNKNOWN MICROBIAL PATHOGEN IN A LUNG TRANSPLANT RECIPIENT: A CASE REPORT

TOPIC: Transplantation TYPE: Fellow Case Reports INTRODUCTION: Lung transplant recipients are at an increased risk for microbial infection, which may at times be difficult to isolate or properly identify, even with repeat transbronchial biopsies (1). CASE PRESENTATION: We reviewed the unique, potential route of transmission and infectious disease course of an enigmatic microbial pathogen that was challenging to identify and associated with an abscess of the lung allograft in a 59-year-old bilateral lung re-transplant recipient. Interestingly, the patient reported having multiple pets at home, including dogs, lizards, cows, horses, and chickens residing on her property, which may have been a source of infection. DISCUSSION: This lung re-transplant recipient presented to our advanced lung disease center at 9-years post-transplant with complaints of sudden fever and chills alongside a 2-week history of productive cough with yellow-tinged sputum. Maintenance immunosuppression consisted of tacrolimus, sirolimus, and prednisone. The patient denied unintentional weight loss, night sweats, or known tuberculosis contacts or exposures;COVID-19 testing was negative in the interim. On thoracic imaging (Figure A), a right upper lobe cavitary lesion was identified. Bronchoscopy was negative for microorganismal growth. She was treated empirically with meropenem, isoniazid, and amikacin. The fever resolved, but the patient reported continued malaise over the next several weeks. Repeated bronchoscopies failed to identify any microorganisms. After six weeks of antibiotic therapy, the size of the lung abscess decreased (Figure B), but all cultures and transbronchial biopsies had failed to determine the infectious origin. The only note regarding her history prior to presentation was that she performed mouth-to-mouth resuscitation on her pet dog who unexpectantly collapsed. It is surmised that this event served as the basis for an oral transmission of a microbial pathogen. CONCLUSIONS: Lung abscesses are generally an early complication in the post-lung transplant period, yet our patient seemingly developed an abscess from an unknown microbial infection at 9-years post-transplant, potentially from a zoonotic source. Although infrequently observed, lung transplant recipients (and other immunosuppressed groups) may be at risk for severe harm or prolonged infection due to direct zoonosis. REFERENCE #1: Påhlman LI, Manoharan L, Aspelund AS. Divergent airway microbiomes in lung transplant recipients with or without pulmonary infection. Respir Res. 2021 Apr 23;22(1):118. doi: 10.1186/s12931-021-01724-w. PMID: 33892717. DISCLOSURES: No relevant relationships by Ashwini Arjuna, source=Web Response No relevant relationships by David Bowman, source=Web Response No relevant relationships by Michael Olson, source=Web Response No relevant relationships by Ali Saeed, source=Web Response

Coccidioidomycosis in an Immunocompetent Host during the COVID-19 Era

Introduction: Coccidioides immitis and posadasii are dimorphic fungi endemic to the southwestern United States. Most immunocompetent hosts who contract coccidioidomycosis will clear the infection without symptoms. We detail the case of an immunocompetent, 56-year-old female who presented with symptoms of lower respiratory tract infection and concern for COVID-19 infection given significant exposure history. Case Description: The patient was referred to our advanced lung disease center (located in the southwestern United States) for subacute, productive cough associated with clear-yellow phlegm, dyspnea on exertion, infrequent night sweats, and abnormal chest x-ray (Figure A). The patient denied any history of fever, chills, hemoptysis, unintentional weight loss, or chest pain. Six-weeks prior to admission, the patient had significant exposure to multiple symptomatic persons with COVID-19. Two RT-PCR tests for COVID-19 to date were ruled negative, and a third test performed on admission was also negative. Computed tomography of the chest revealed right upper lobe cavitary consolidation with surrounding nodules bilaterally (Figure B). Sputum smear was negative for acid-fast bacillus or other bacterial organisms, prompting a bronchoscopy with bronchoalveolar lavage. Results demonstrated fungal cultures of Coccidioides immitis/posadasii. The patient also had significant IgG antibodies against Coccidioides species. She was started on therapeutic doses of fluconazole with a gradual improvement in symptoms. Discussion: History of significant exposure to COVID-19 warrants prompt and thorough investigation for disease status. Nonetheless, clinicians should still maintain a high suspicion and vigilance for excluding other, potentially treatable infectious etiologies, even regional endemic fungal infections that tend to manifest without symptoms.

Two Cases of Spontaneous Bleeding in Lung Transplant Recipients Treated with Systemic Anticoagulation for COVID-19

Introduction COVID-19 promotes inflammation and a hypercoagulable state. Antithrombotic therapies may be administered for thromboprophylaxis in those with severe infection requiring hospitalization. Spontaneous bleeding is an infrequent, yet life-threatening complication in patients receiving systemic anticoagulation. Case Report Two bilateral lung transplant recipients - 77-year-old female with idiopathic pulmonary fibrosis (patient A) and 69-year-old male with chronic obstructive pulmonary disease (patient B) - each presented with several days’ history of dyspnea, cough, and fatigue at 29-months and 11-months post-transplant, respectively;RT-PCR was positive for SARS-CoV-2 infection in both. Over the course of the next few days, patient A rapidly deteriorated with need for intubation despite initial treatment with antibiotics and corticotherapy. Patient B experienced gradual worsening of respiratory symptoms, which required high-flow oxygen supplementation and IV antibiotics. Inflammatory markers were elevated in both patients, and CT of the chest was consistent with atypical pneumonia in each. Patient A received convalescent plasma as a rescue therapy, and patient B received remdesivir with convalescent plasma. Given the hypercoagulable state in each, patient A and B received enoxaparin and IV heparin, respectively. Slowly, hemoglobin and platelet counts dropped in both patients, with need for transfusion and hemodynamic support. CT of the abdomen revealed a left gluteal intramuscular hematoma in patient A;CT of the chest, abdomen, and pelvis revealed a spontaneous chest wall hematoma and small area of retroperitoneal bleeding in patient B (Figure 1A and B). Summary These cases raise awareness for the viral-induced hypercoagulable state observed during the disease course. Clinicians should be cautious to avoid any hemorrhagic complications associated with thromboprophylaxis in selected cases, particularly in at-risk immunosuppressed patients.

International Experience with Lung Transplantation for COVID-19 Associated Acute Respiratory Distress Syndrome

Purpose The COVID-19 pandemic has infected millions of people across the world and caused several thousands of deaths. Given advances in extracorporeal life support technology, ECMO for COVID-19 acute respiratory distress syndrome (ARDS) has proven to be successful in sustaining life, however, has left a significant number of patients fully depended on devices and incapable of being weaned. Lung transplantation, as a well-established therapy for end-stage lung disease, has been considered for some patients with COVID-19 ARDS in the absence of lung recovery and the presence of findings suggestive of end-stage lung disease. Methods This is an International collaborative effort to assess the role of lung transplantation in COVID-19 ARDS. There is worldwide representation with centers from US (3), Europe (2) and Asia (1). Patients with COVID-19 ARDS supported on ECMO and/or mechanical ventilation who were deemed unweanable and developed features of end-stage lung disease were evaluated for lung transplantation. We followed ISHLT conventional recipient selection criteria recommendations and a 2 negative COVID-19 PCRs from bronchoalveaolar lavage or viral culture depending on medical urgency. Endpoints We will present demographics, intraoperative challenges, primary graft dysfunction, postoperative complications, survival and functional outcomes of patients with COVID-19 ARDS who underwent lung transplantation. Additionally, referral patterns, reasons for listing denial and waitlist outcomes will be presented. So far, this collaborative group has transplanted 17 patients. There have been no deaths on the waitlist, there was one post-transplant mortality at day 61. Ten patients have been discharged from the hospital and are doing well. Six patients are recovering well however less than 30 days post-transplantation and remain admitted.