Guillain-Barré Syndrome after Mrna-1273 Covid-19 Vaccine Booster in an Immunosuppressed Double Lung Transplant Recipient

Guillain-Barré Syndrome (GBS) is an immune-mediated neurological disorder with an estimated incidence of 1 to 2 per 100,000 person-years. GBS is characterized by progressive and symmetric ascending muscle weakness, areflexia, sensory symptoms, and dysautonomia. Antecedent infection or vaccination may trigger GBS;however, there are few reports of GBS after either mRNA-1273 (Moderna) or mRNA-BNT-162b2 (Pfizer-BioNTech) COVID-19 vaccines (1.21 and 1.05 GBS reports per million doses, respectively). A 2021 analysis of the Vaccine Safety Datalink found no increased risk of GBS after vaccination with either of the vaccines. We report a case of GBS after a third dose of mRNA-1273 in a lung transplant recipient (LTxR). A 38-year-old LTxR on standard 3-drug immunosuppression presented to clinic complaining of back pain 2 weeks after receiving a third dose of mRNA-1273. His pain was treated with analgesics;however, a week later he presented to the Emergency Department (ED) with worsening back pain, myalgias, and lower extremity weakness. Neurology was consulted and he underwent an extensive work-up including screening serologies for vasculitis and myasthenia gravis and blood tests for B12, folate, and creatinine kinase (CK) levels. Viral and bacterial infections were ruled out. A spinal MRI showed no evidence of nerve root enhancement;a lumbar puncture revealed albuminocytologic dissociation with a high protein level of 113 mg/dL and cell count of 1/uL. Autoimmune and paraneoplastic panels as well as oligoclonal bands were negative. He was diagnosed with GBS and completed a 5-day IVIG course which led to transient symptomatic improvement. Four weeks later, he reported to the ED in a wheel chair after multiple falls and an inability to stand or walk. His neurological exam showed symmetric ascending weakness of lower extremities that was worse distally, reduced hand-grip strength, and areflexia. Electromyography showed evidence of acute inflammatory demyelinating polyneuropathy, confirming the GBS diagnosis. An additional 2-day IVIG course and intensive outpatient physical therapy led to neurologic improvement. Although current data does not suggest an increased risk of GBS after mRNA COVID-19 vaccines, GBS should be considered in LTxRs who develop symmetric motor and sensory deficits after vaccination. [ABSTRACT 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

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

Progressive Multifocal Leukoencephalopathy Presenting as Expressive Aphasia in a Lung Transplant Recipient

Introduction: Progressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR). Case Report: A 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits. PML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue;however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management.

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.

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.

SARS-CoV-2 Re-Infection in a Lung Transplant Recipient

Introduction Since the onset of the SARS-CoV-2 pandemic, increasing evidence has shown waning immunity after initial SARS-CoV-2 infection, and re-infection in patients with a prior history of COVID-19 has been reported. We report a case of SARS-CoV-2 re-infection in a lung transplant recipient 3 months after initial illness. Case Report The patient is a 56-year-old man with a history of bilateral lung transplant in August 2018 for idiopathic pulmonary fibrosis. His post-transplant course was complicated by insulin-dependent diabetes mellitus (HbA1c 5.8%), chronic renal insufficiency (eGFR nadir 48 mL/min/1.73m2), and peripheral arterial disease requiring bilateral below-knee amputations. At the time of transplant, he was induced with basiliximab and remained on standard 3-drug immunosuppression with mycophenolate mofetil (500 mg BID), prednisone (5 mg daily), and tacrolimus. He contracted SARS-CoV-2 from his wife and tested positive for the virus on July 2, 2020 after presenting to the emergency department (ED) with headache, chills, nausea, body aches, shortness of breath, and generalized weakness. His oxygen saturation and chest X-ray were normal, and he was therefore discharged from the ED to recover at home. His symptoms resolved 17 days after diagnosis and serial SARS-CoV-2 testing via nasal washing were positive on July 16, 2020 and negative on July 30, 2020 and August 11, 2020. In addition, on October 21, 2020, he tested positive for SARS-CoV-2 antibodies (3.41, positive: index ≥1.4). On October 23, 2020, he presented to the ED with generalized chest pain, low-grade fever (100.1F), dyspnea, and weakness. His nasal swab was positive for SARS-CoV-2 and CT of the chest showed bibasilar ground-glass opacities consistent with atypical infection vs. atelectasis. His labs were notable for a CRP of 132 mg/L, ferritin of 2,307 ng/mL, LDH 304 units/L, D-dimer 240 ng/mL, and procalcitonin of 0.05 ng/mL. He was admitted for monitoring and treated with remdesivir, corticosteroids, and anticoagulation. Summary We present a case of SARS-CoV-2 re-infection 3 months after initial illness in a lung transplant recipient living in a high-incidence area. Unexpectedly, recurrent infection occurred despite development of SARS-CoV-2 antibodies. This case speaks to the vulnerability of this patient population to COVID-19 and the need for ongoing precautions to prevent infection even among patients who have seroconverted.