The First Case of Haemophagocytic Lymphohistiocytosis Triggered by the Booster Dose of Anti-SARS-CoV-2 Vaccine in a Patient with β-Thalassemia

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening systemic hyperinflammatory disease, which can have several aetiologies. Clinical case: a 48-year-old woman affected by a transfusion-dependent β-thalassemia was hospitalized in our haematology unit presenting with intermittent fever, haepatosplenomegaly and pancytopenia, which developed a few days after the booster dose of anti-SARS-CoV-2 mRNA vaccine. The investigations performed during hospitalization led to a diagnosis of HLH and steroid therapy where IV dexam-ethasone was initiated and provided benefits. Conclusions: the severity of HLH mandates early treatment, but the management of patients with post-vaccine HLH is still challenging and requires further study. No cases of HLH in patients with thalassemia were previously described.

Prolonged Thrombocytopenia in a Case of MIS-C in a Vaccinated Child.

Multisystem inflammatory syndrome in children (MIS-C) has been extensively described in patients following severe acute respiratory syndrome coronavirus 2 infection. There are now questions about what MIS-C may look like in vaccinated children. Multisystem inflammatory syndrome in children has many clinical and laboratory features in common with other inflammatory disorders including Kawasaki disease and toxic shock syndrome. Rheumatologic conditions can present with similar musculoskeletal complaints and elevated inflammatory markers. Laboratory markers and clinical symptoms of MIS-C usually improve once therapy is begun. We describe a child with persistent thrombocytopenia as an example of variable presentation of MIS-C in vaccinated children. This case report discusses an atypical progression of MIS-C in a vaccinated child with a known prior positive COVID-19 polymerase chain reaction (PCR) test. She presented with nonspecific abdominal pain and fever and was found to have elevated inflammatory markers, lymphopenia, and thrombocytopenia. Intravenous immunoglobulin and steroid treatment failed to induce rapid recovery in her clinical condition or thrombocytopenia. Rheumatologic, hematologic, oncologic, and infectious causes were considered and worked up due to the uncertainty of her case and persistence of pancytopenia but ultimately were ruled out with extensive testing and monitoring. It was key to include a broad differential including viral-induced bone marrow suppression, idiopathic thrombocytopenic purpura, secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, and malignancy. The spectrum of MIS-C and response to treatment continues to evolve, and prior vaccination in this child's case complicated the clinical picture further. Additional evaluation of MIS-C in vaccinated cases will permit characterization of the range of MIS-C presentation and response to standard therapy.

Prolonged fever and inflammation in a young child in the midst of the pandemic - it's not always MIS-C

Case Report: Prolonged fever in children is a symptom that is seen in many different diseases, infections, malignancies, and autoimmune conditions. This can, at times, make the correct diagnosis challenging. A previously healthy 10-year-old male was transferred to our institution with one week history of fever, fatigue, abdominal pain, and vomiting. Laboratory studies demonstrated pancytopenia, transaminitis, electrolyte abnormalities, elevated pro-inflammatory markers & D-Dimer, and hypoalbuminemia. COVID-19 IgG was reactive. Due to the severity in presentation the patient was transferred to the ICU with a presumptive diagnosis of MIS-C. Hewas started on IVIG as well as a five-day course of high-dose methylprednisolone per protocol. Aspirin was added, but later discontinued, due to worsening thrombocytopenia. CT imaging with contrast showed small bilateral pleural effusions & periportal edema, mild splenomegaly, and echocardiogram showed diffuse dilation of the left main and left anterior descending arteries. Given the laboratory findings the differential diagnosis was expanded, Ehrlichia caffeensis serology was sent and empiric Doxycycline started. EBV Nuclear Antigen IgG antibody and EBV Viral Capsid Antigen IgM Antibody resulted as positive suggesting recent or reactivated infection. Respiratory viral PCR with COVID-19, Cytomegalovirus and Parvovirus PCR were negative. Despite initial treatment, the patient continued to have persistent fever, severe pancytopenia, and high ferritin up to 24 426 ng/mL, raising suspicion for Haemophagocytic Lymphohistiocytosis (HLH). Soluble interleukin-2 level was elevated & his presentation was then considered to be more consistent with HLH given that he met 6/8 criteria. Screening for primary HLH including CD107a, perforin and granzyme B, SAP, and XIAP resulted in the latter three being normal but CD107a was abnormal. Next generation sequencing for primary criteria was negative. E. Chaffeensis resulted positive: IgM 1:80, IgG 1:256. MIS-C and HLH have overlapping features but differ in some clinical manifestations. Timely recognition and management is paramount as the management differs. This case illustrates the importance of performing a broad search for potential causes, allowing for appropriate and timely treatment. COVID-19 serology alone should not be the basis for diagnosis of MIS-C in a patient with fever and inflammation. This is important as SARS-CoV2 becomes endemic. Infections such as EBV and Ehrlichiosis should be on the differential particularly in endemic areas and during seasons of higher prevalence for the latter, as these have been well documented to cause HLH. Copyright © 2023 Southern Society for Clinical Investigation.

Hemophagocytic Lymphohistiocytosis Following COVID-19 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with multiple inflammatory symptoms involving several organ systems, including hematologic manifestations. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by excessive inflammation in the absence of immune regulation. We present the case of a patient with HLH secondary to dysregulated inflammatory response following COVID-19; we also describe the diagnostic and management challenges associated with the condition.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

COVID-19 and Subsequent Development of Pancytopenia With Concurrent Disseminated Intravascular Coagulation.

Complications resulting from coronavirus disease 2019 (COVID-19) sequelae have been well documented. These include blood conditions such as lymphopenia, thrombocytopenia, and hypercoagulability. Less common problems that may arise are disseminated intravascular coagulation (DIC), immune thrombocytopenic purpura (ITP), and pancytopenia. Furthermore, the majority of COVID-19 patients to develop pancytopenia have been immunosuppressed. We present a case of a previously immunocompetent patient who subsequently developed pancytopenia, DIC, as well as symptoms of ITP one month after being diagnosed with COVID-19.

SEVERE COVID-19 COMPLICATED WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A CASE REPORT

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Worsening respiratory disease is the most common complication of severe COVID-19. However, when patients develop multi-organ dysfunction, clinicians must have a high index of suspicion for rare syndromes such as hemophagocytic lymphohistiocytosis (HLH). CASE PRESENTATION: A 39-year-old male smoker presented with 1 week of shortness of breath and malaise. Initial physical examination revealed T 37.3 C, pulse 85 min-1, respiratory rate 18 breaths min-1, SPO2 96% and clear breath sounds without labored respirations. Chest X-ray showed bilateral patchy airspace opacities in the mid and lower lung fields. A SARS-COV2 PCR test was positive. The patient was prescribed antibiotics and discharged home. Subsequently, the patient's symptoms worsened and he presented 1 week later with SPO2 90% (O2 10 L/min via nasal cannula). He was admitted to the hospital with COVID-19 pneumonia and began remdesivir, barcitinib, systemic steroids, albuterol and IV antibiotics. On admission his complete blood count and complete metabolic panel were unremarkable. After 3 weeks of hospitalization, he developed multi-organ failure with acute liver injury, acute kidney injury, shock, pancytopenia and worsening hypoxemia leading to endotracheal intubation and mechanical ventilation. CT chest imaging showed bilateral ground glass opacities in the lungs with superimposed consolidation (figure 1). Blood cultures remained sterile, HIV, hepatitis B and C viral serologies were negative. Serum viral polymerase chain reaction detected Herpes Simplex Virus-1 (HSV-1) and Epstein Barr Virus (EBV) infections. Trans-jugular liver biopsy confirmed HSV-1 hepatitis and showed sub-massive hemorrhagic necrosis of the liver (figure 2). Bone marrow biopsy demonstrated phagocytic histiocytes engulfing red blood cells and platelets consistent with HLH (figure 3). The patient began HLH targeted therapy with anakinra and high dose steroids. Despite this, the patient continued to deteriorate, developed refractory shock and subsequently expired. DISCUSSION: HLH is a rare disease of the immune system in which a genetic or infectious trigger causes uncontrolled T cell activation. T cell activation triggers macrophage activation, cytokine storm and macrophage phagocytosis of erythrocytes, leukocytes, platelets and precursors in the bone marrow and other tissues. If the syndrome is unrecognized, it can quickly lead to multi-organ failure and death. EBV is the most common infectious trigger of HLH;however, infection with HSV-1 and SARS-COV-2 viruses have been identified as rare and independent causes. CONCLUSIONS: This case illustrates the high index of suspicion providers should have for HLH in patients with severe COVID-19 who develop multi-organ injuries. Once HLH is suspected, prompt initiation of HLH-94 protocol with etoposide and dexamethasone may be lifesaving. For those patients with liver failure, other agents (e.g. anakinra) may be provided. Reference #1: Ramos-Casals M, Brito-Zerón P, López-Guillermo A, et al.: Adult haemophagocytic syndrome. Lancet 2014;383:1503–1516 Reference #2: Risma K, Jordan MB: Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr 2012;24:9–15 Reference #3: Trottestam H, Horne A, Aricò M, et al.: Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 2011;118:4577–4584 DISCLOSURES: No relevant relationships by Erin Biringen No relevant relationships by Christine Brennan No relevant relationships by Joann Hutto No relevant relationships by Daniel Puebla Neira

DOES COVID-19 INCREASE YOUR RISK OF DEVELOPING HAIRY CELL LEUKEMIA?

SESSION TITLE: Pathology Identifying Chest Infections Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Coronavirus disease 2019 (COVID-19) patients presented in a wide variety and had multiple complications. The well-known associations found are myocardial infraction, pulmonary embolism, meningitis, encephalitis. We are presenting a new diagnosis of Hairy cell leukemia in COVID 19 patients. CASE PRESENTATION: We present a 55-year-old pleasant female with no significant past medical history;non immunocompromised who presented with 7 days history of shortness of breath on exertion, fever, fatigue, and cough. Her physical exam was unremarkable, but she was desaturating on presentation hence was placed on oxygen via nasal canula. On work up she tested positive for COVID-19. Initial chest Xray revealed bilateral diffuse pulmonary infiltrates. Complete blood count (CBC) showed pancytopenia with white blood cell count (WBC) 0.8 × 103/μL (4–10 × 103/μL), absolute neutrophil count (ANC) 0.5 × 103/μL (2–7 × 103/μL), hemoglobin (Hgb) 10.4 g/dL (13.0–17.0 g/dL), and platelet count 156× 103/μL (150–400 × 103/μL). She received treatment for COVID 19 pneumonia as per the protocol. On repeat CBC check there was minimal improvement in her counts. The rest of her WBC differential showed a lymphopenia with ALC ranging from 350–500 with no other obvious immature cells or blasts to suggest a myeloid neoplasm such as acute leukemia. Work-up including vitamin B12, folate, TSH, EBV, ANA, and hepatitis were unremarkable. She also received treatment with supportive granulocyte colony-stimulating factor (G-CSF) but there was minimal improvement. As her pancytopenia persisted for 1 week the peripheral blood smear was done which showed pancytopenia (with prominent red cell agglutination, with rare, atypical lymphoid cells with multiple hairy projections. A bone marrow (BM) aspirate was hypocellular showing markedly decreased trilineage hematopoiesis with atypical lymphoid cells with oval or indented nuclear borders, unclumped chromatin, absent or inconspicuous nucleoli, and moderate to abundant pale blue cytoplasm with multiple circumferential cytoplasmic projections (hairy cells) [Figure:1]. The hairy cells showed strong positivity for CD20[Figure:2]. She was followed up by hematology and was started on treatment. DISCUSSION: Hairy cell leukemia (HCL) is a rare B cell lymphoproliferative disease with marked cytopenia and circulating leukemia cells. Multiple viruses (EBV, HTLV1) were found to be associated with multiple different malignancies. It is found that COVID19 is not associated with any malignancy so far, but our patient got diagnosed with HCL during COVID19 illness. CONCLUSIONS: The association of HCL could be an incidental finding but we need to do further studies to clarify the associations Reference #1: Kohla, Samah et al. "A Rare Case of Hairy Cell Leukemia with Unusual Loss of CD123 Associated with COVID-19 at the Time of Presentation.” Case reports in oncology vol. 13,3 1430-1440. 4 Dec. 2020, doi:10.1159/000512830 DISCLOSURES: No relevant relationships by Apurwa Karki No relevant relationships by Shobha Mandal No relevant relationships by Rajamurugan Meenakshisundaram

A CHALLENGING CASE OF MYCOBACTERIUM TB-INDUCED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation in response to a variety of insults including malignant, autoimmune and infectious processes. The most common infectious trigger is a viral infection, but other pathogens have also been implicated including Mycobacterium tuberculosis (MTB) CASE PRESENTATION: 62-year-old male from Bangladesh presented due to lethargy, weakness, and anorexia for several weeks. He also reported fevers, diarrhea, and unintentional weight loss. On examination, he appeared acutely ill with diffuse bibasilar crackles on lung exam. Labs showed platelets of 132, ESR 45 mm/hr, CRP 9.6mg/dL, ferritin 1,765ng/mL and transaminitis. A viral panel was positive for Rhinovirus. Computed tomography (CT) of the chest showed diffuse bilateral ground-glass opacities and he was started on antibiotics for pneumonia. On day 3, his respiratory status worsened and he was emergently intubated. He underwent bronchoscopy and bronchoalveolar lavage (BAL) and started on high-dose steroids for possible hypersensitivity pneumonitis. On day 5, he was extubated to nasal cannula, however, his condition worsened despite treatment. Extensive infectious workup, including HIV, Covid and P jirovecii PCR, sputum, and blood cultures, and preliminary AFB smear were negative. Subsequent labs noted rising ferritin levels (4,164 ng/mL), high triglycerides, pancytopenia and transaminitis. Calculated H score was 211 which gave a 93-96% probability of HLH. Initiation of Etoposide was discussed but family deferred. He was later transferred to another facility. On follow-up, IL-2 receptor antibodies were elevated, bone marrow biopsy showed hemophagocytosis and necrotizing granulomas. He was intubated for worsening hypoxemia. Repeat bronchoscopy and BAL analysis showed many acid-fast bacilli. Anti TB treatment (ATT) was deferred due to his critical state. He further declined and eventually expired. DISCUSSION: The exact mechanism for which MTB triggers HLH is unclear, however, it is thought that MTB serves as an obligate intracellular pathogen after phagocytosis by phagocytic cells to induce TH1-mediated cytotoxicity, activating macrophages and NK cells, further releasing a large quantity of cytokines and chemokines. The lack of specific clinical signs, low sensitivity for acid-fast staining, and time-consuming culture make the diagnosis of TB-HLH difficult. However, the use of NAATs has improved the yield of sputum testing. Exceedingly high ferritin levels should serve as a red flag in cases of undetermined diagnosis. Moreso, Cytopenias, elevated LFTs, and coagulation dysfunction are other clues that a diagnosis of HLH should be on the differential. It is believed that early and effective ATT is the key to preventing HLH in TB patients. CONCLUSIONS: It is paramount to both recognize the features of TB as well as HLH as early diagnosis and treatment favor better outcomes. Reference #1: Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A. Hemophagocytic Lymphohistiocytosis: An Unusual Complication in Disseminated Mycobacterium Tuberculosis. Lung India (2015) 32(6):593–601. doi: 10.4103/0970-2113.168100 Reference #2: Dalugama, C., Gawarammana, I.B. Fever with pancytopenia: unusual presentation of extrapulmonary tuberculosis: a case report. J Med Case Reports 12, 58 (2018). https://doi.org/10.1186/s13256-018-1596-0 Reference #3: O M P Jolobe, Timely recognition of hematophagocytosis attributable to coexistence of lymphoma and tuberculosis, QJM: An International Journal of Medicine, Volume 112, Issue 4, April 2019, Page 315, https://doi.org/10.1093/qjmed/hcy198 DISCLOSURES: No relevant relationships by Katherine Acosta No relevant relationships by Chika Winifred Akabusi No relevant relationships by Uma Medapati No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Busala Oke No relevant relationships by Mar o Torres

CYSTIC LUNG DISEASE IN A YOUNG MALE WITH SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Challenges in Cystic Fibrosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pulmonary involvement in Systemic Lupus Erythematosus (SLE) is seen in 30-50% of patients (most commonly Nonspecific Interstitial Pneumonitis) but cystic lung disease is extremely rare (1). Lymphoid interstitial pneumonia (LIP) is an inflammatory lung disease that is characterized by infiltration of lymphocytes and plasma cells (2), and associated with lung cysts. Oftentimes, it is associated with HIV, lymphoma, and primary Sjogren's Syndrome (SS) (2), however there are rare reports of LIP associated with SLE (1). We present a case of a young male with incidental lung cysts who was found to have a new diagnosis of SLE. CASE PRESENTATION: A 24-year-old male with a past medical history of premature birth at 5 months and prior mild COVID-19 infection presented with 3 weeks of abdominal pain, nausea, vomiting, fever, and unintentional 15-pound weight loss. He endorsed dry mouth, frequent cavities, and a new rash involving his chest, face, and lower extremities. Physical exam was significant for malar rash and dry mucous membranes. Labs revealed pancytopenia, sedimentation rate 61 mm/hour and C-reactive protein 5.54 mg/L. Computed tomography (CT) of the chest showed several thin-walled cysts in all bilateral lung lobes (predominant in right upper lobe) and bilateral axillary lymph nodes [Figure 1]. CT abdomen and pelvis was unremarkable. Autoimmune work-up resulted in a positive antinuclear antibody >1:1280, double stranded DNA antibody elevated at 34, elevated SSA and SSB antibodies (>8.0 and 1.4 respectively), and decreased Complement 3 (59.5 mg/dl) and 4 (10.1 mg/dl) levels. Peripheral smear, right axillary lymph node and bone marrow biopsies were negative for malignancy. He was started on prednisone and Plaquenil with symptomatic improvement. There is high suspicion of LIP given the clinical and radiological findings. He will follow up in clinic to obtain PFTs and schedule a lung biopsy. DISCUSSION: Interstitial lung disease in SLE presents in middle-aged patients at a later part of their disease course, with a female preponderance (2,3). An initial presentation of SLE and secondary SS in a young male and associated cystic lung disease is rare. The suspicion for LIP in association with SLE is high in our patient given variable size and distribution of lung cysts and coexisting secondary Sjogren's syndrome, although no ground glass or nodular opacities were found on CT chest as reported in typical LIP (3). Though this patient has no pulmonary symptoms, cysts/LIP in SLE tend to progress and have a high incidence of developing lymphomas, gammaglobulinemia and amyloidosis (2,3). CONCLUSIONS: It is important to establish a histopathological diagnosis and obtain baseline PFTs to monitor pulmonary disease manifestations. In addition to controlling the primary disease with antirheumatic drugs, steroids have been found to be useful in acute pulmonary flares (2). Reference #1: Maeda R, Isowa N, Miura H, Tokuyasu H. Systemic lupus erythematosus with multiple lung cysts. Interact Cardiovasc Thorac Surg. 2009 Jun;8(6):701-2. doi: 10.1510/icvts.2008.200055. Epub 2009 Mar 12. PMID: 19282324. Reference #2: Yood RA, Steigman DM, Gill LR. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus. Lupus. 1995 Apr;4(2):161-3. doi: 10.1177/096120339500400217. PMID: 7795624. Reference #3: Filipek MS, Thompson ME, Wang PL, Gosselin MV, L Primack S. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus: radiographic and high-resolution CT findings. J Thorac Imaging. 2004 Jul;19(3):200-3. doi: 10.1097/01.rti.0000099464.94973.51. PMID: 15273618. DISCLOSURES: No relevant relationships by Matthew Fain No relevant relationships by Christina Fanous No relevant relationships by Rathnavali Katragadda No relevant relationships by CHRISELYN PALMA

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

A CASE OF LOMUSTINE-INDUCED PNEUMONITIS

SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Lomustine, a nitrosurea, inhibits DNA, RNA, and protein synthesis by carbamylation and alkylation, leading to cytotoxic effects 1, 3. Its concentration is high in the central nervous system (CNS) and therefore is commonly used for the management of CNS tumors including recurrent glioblastoma. While known side effects include pancytopenia, few pulmonary toxicities have been reported. This case is a rare example of lomustine induced pneumonitis. CASE PRESENTATION: A 54-year-old female with a history of glioblastoma, treated with a combination of surgical resection, radiation therapy, and temozolomide followed by stereotactic surgery and bevacizumab after disease recurrence, developed progressive dyspnea after initiating lomustine. She had received one dose of lomustine 90 mg/m2 two months prior to developing dyspnea upon exertion. At baseline, she was an active individual who played sports. A chest computed tomography (CT) scan preformed ten months prior was without any parenchymal abnormalities, and pulmonary function tests (PFTs) two months prior were normal with an adjusted DLCO of 15.4 mL/mmHg/min (88%). Repeat chest CT revealed diffuse ground glass opacities, and repeat PFTs showed a moderately impaired adjusted DLCO of 10.4 mL/mmHg/min (60%). Other lab evaluation, CBC, BNP, troponin, and COVID PCR, were negative. After receiving six weeks of steroids, there was resolution of CT findings, improvement of DLCO, and relief from symptoms. DISCUSSION: More common adverse effects of lomustine are GI discomfort and pancytopenia. It is less widely documented to cause pulmonary toxicity compared to its chemical relative carmustine 1, 3. This is perhaps due to decreased alkylation ability and penetration into the lung tissue by lomustine7. There have been few case reports revealing pneumonitis and pulmonary fibrosis. Lomustine induced pneumonitis induces acute parenchymal changes of the lung demonstrated by characteristic symptoms and imaging/biopsies abnormalities after initiation of a drug. 2 Findings include breathlessness, dyspnea upon exertion, cough, hypoxia, crackles upon lung auscultation. PFT's may show a restrictive pattern with decreased FEV1/FVC ratio and DLCO. Imaging may reveal diffuse groundglass opacities, traction bronchiectasis, interlobular septal thickening, and honeycombing. Bronchoscopy with lavage would rule out infection. Management involves discontinuation of culprit medication, immunosuppression, and supportive therapies to alleviate respiratory discomfort. Lack of treatment may produce complications of acute respiratory distress syndrome and fibrosis. CONCLUSIONS: Lomustine is an essential treatment drug for recurrent CNS tumors. Toxicities such as pneumonitis have been rarely demonstrated. Timely recognition of pneumonitis features is key to treat this complication, improve quality of life, and prevent permanent lung compromise. Reference #1: Dent RG. Fatal pulmonary toxic effects of lomustine. British medical journal. 1982;DOI:10.1136/thx.37.8.627 Reference #2: Skeoch S, Weatherley N, Swift AJ, Oldroyd A, Johns C, Hayton, C, et al. Drug-Induced Interstitial Lung Disease: A Systemic Review. Journal of Clinical Medicine. 2018;doi 10.3390/jcm7100356 Reference #3: Weiss RB, Issell BF. The nitrosureas: carmustine and lomustine. Cancer treatment reviews. 1982;https://doi.org/10.1016/S0305-7372(82)80043-1 DISCLOSURES: No relevant relationships by Sukhdeep Kaur No relevant relationships by Chelsea Kennedy-Snodgrass No relevant relationships by Sarun Thomas

SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN A PATIENT WITH COVID-19 AND HERPES SIMPLEX VIRUS (HSV): A CASE REPORT

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome caused by severe, dysregulated hypercytokinemia. This can be associated with genetic defects or immunologic triggers such as infection, malignancy or autoimmune disorder. The clinical picture consists of multi-organ failure including fever, hepatosplenomegaly, cytopenia,hypertriglyceridemia, hemophagocytosis, high ferritin and IL-2 levels, neurological and liver dysfunction. We present a case of a patient with HLH in the setting of Herpes Simplex Virus (HSV) and SARS-CoV-2 co-infection. CASE PRESENTATION: A 39-year-old male presented to the ER with dyspnea and was found to have COVID-19 pneumonia. He had worsening hypoxemia and was admitted to ICU. He rapidly developed multi-system organ failure (MSOF)including severe hepatitis with AST 13,950 U/L and ALT 10,000 U/L, pancytopenia (Hb 12.9 g/dL, WBC 1.7 K/uL, platelet 15,000 K/uL), acute kidney injury (Cr 6.61 mg/dL), and severe ARDS requiring mechanical ventilation. Abdominal ultrasonography showed splenomegaly. Blood HSV1 DNA PCR was positive with liver biopsy revealing viral inclusions consistent with HSV hepatitis. He had elevated ferritin > 100,000 ug/L and LDH > 2500 U/L. Bone marrow biopsy demonstrated hemophagocytosis and trilineage hematopoiesis. He met 6 of 8 diagnostic criteria for HLH per the HLH-2004 protocol. He received dexamethasone. Risks and benefits of HLH-specific therapy were considered in the setting of liver dysfunction and the decision was made to withhold etoposide and administer anakinra. He died of refractory septic shock and disseminated intravascular coagulopathy. DISCUSSION: Diagnosis of HLH can be challenging due to its rarity and the clinical picture may be initially attributed to sepsis in the presence of infection, as in our patient who had COVID-19 infection and HSV hepatitis. However, a ferritin level >10,000 ng/mL is 90% sensitive and 96 % specific for HLH, with very minimal overlap with sepsis, infections, and liver failure. Additionally, infection is a known trigger of HLH. Despite high mortality without therapy, survival can be significantly increased with HLH-specific therapy, such as etoposide. Treatment with etoposide in the setting of severe liver disease can raise concern because it is metabolized by the liver but it is an essential component of optimal therapy and can be considered in patients with hepatic dysfunction with dose reduction. CONCLUSIONS: Our case highlights the importance of maintaining a high index of suspicion for HLH in critically ill patients with MSOF and liver failure, despite an apparent infectious etiology. This may allow timely diagnosis, early referral to a specialist center and consideration of HLH-specific therapy such as etoposide despite liver dysfunction, to prevent high morbidity and mortality in this potentially fatal disease. Reference #1: Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009;:127. DISCLOSURES: No relevant relationships by Abdul Khan No relevant relationships by Nehan Sher No relevant relationships by yuttiwat vorakunthada

LUNG INVOLVEMENT in VEXAS SYNDROME

Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.

LONG-TERM EFFICACY and SAFETY of UPADACITINIB in PATIENTS with PSORIATIC ARTHRITIS REFRACTORY to BIOLOGIC THERAPIES: 2-YEAR RESULTS from the PHASE 3 SELECT-PSA 2 STUDY

Background: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheu-matic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1 Objectives: To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods: Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results: A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion: In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identifed in this long-term extension.

Coronavirus-2019 Disease with Pancytopenia with Leptospirosis and Herpes Simplex Virus Co-infection

Aim and background: COVID-19 pandemic has affected the whole world. Besides COVID, many infections may emerge during the course of the disease. Lymphopenia, use of immunosuppressants underlying comorbidities, and immune dysregulation secondary to SARS-CoV-2 could be the likely cause of the emergence such infections. We hereby describe a case of COVID-19 disease which presented with pancytopenia and was found to have Leptospirosis and Herpes Simplex Virus co-infection. Case summary: A 23-yearold postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital 2 weeks after a full-term normal vaginal delivery. She developed generalized convulsive status epilepticus on the 10th day of her delivery, which was managed elsewhere with anti-epileptic drugs (AEDs). During her hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic throughout the course of her illness and seizures remained well-controlled on AEDs. On admission to our hospital, she was fully conscious, alert with no focal neurological deficits. Notable findings on evaluation were pancytopenia with megaloblastic features, bilateral pedal edema, and hepatosplenomegaly. NCCT brain was done which was suggestive of subarachnoid hemorrhage (SAH) along bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of abdomen revealed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In the panel sent for pancytopenia workup, IgM anti-HSV 1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies were positive). Workup for tuberculosis was negative. Bone marrow workup revealed features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia with no evidence of hemophagocytosis. Subsequently, IV acyclovir, IV doxycycline, and iron replacement were added. She improved clinically after these therapies and was subsequently discharged in a stable condition. MRI brain with MR angiography and venography done before discharge showed T1 sulcal hyperintensities along bilateral parietooccipital regions suggestive of SAH which was not progressing (as compared to NCCT brain scan done at admission). On day 60 of telephonic follow-up, patient was doing well and leading normal life without any persistence or emergence of symptoms.

Clinical Presentation of Melioidosis: A Case Series

Introduction: Melioidosis is an infectious disease caused by Gramnegative bacterium Burkholderia pseudomallei. It is a potentially fatal disease endemic to tropical and subtropical regions. Bacteria spread by contact with contaminated water and soil. The presentation of this disease is variable ranging from localized infection to fulminant septicemia and multi-organ dysfunction. Objective: The purpose of this study is to look into clinical presentation, treatment, and outcomes of confirmed melioidosis cases in a tertiary care hospital. Materials and methods: This is a retrospective case series of patients in a single tertiary care center between January 2018 and September 2021. We present a series of 19 cases admitted with a confirmed diagnosis of melioidosis. Three of 19 cases discontinued treatment in between but were included in the analysis. Results: We report 19 cases of melioidosis admitted to our hospital in a span of 3 years (17 males and 2 females). The median age of presentation was 47 years. The disease had varied presentation with lung involvement in 11 cases (57%), solid organ abscesses in 8 cases (42%), osteomyelitis and septic arthritis in 5 (26%), and acute pyelonephritis in 2 cases (10%). Lung involvement was seen as consolidation, septic emboli, and solid nodular lesions. Most common risk factor associated with disseminated disease was diabetes. Diabetes was seen in 17 cases (89.4%). All patients had uncontrolled blood sugars and 2 cases presented in DKA. Other comorbidities seen were systemic hypertension (16%), coronary artery disease (10%), chronic liver disease (10%), post COVID (10%), and SLE (5%). ARDS complicating lung condition was seen in 6 patients (54%) of which 3 patients were managed with NIV and 3 patients required invasive mechanical ventilation. AKI was seen in 11 patients (57.8%) of which 8 patients recovered from AKI and 3 patients required renal replacement therapy. One patient with associated lupus nephritis required long-term hemodialysis. Altered liver function test was seen in 11 patients (57.8%). Bone marrow suppression is common. Three patients had pancytopenia and 10 patients had thrombocytopenia. Hyponatremia was the most common electrolyte abnormality seen in 7 patients (36.8%). Of the 19 cases admitted three patients did not continue treatment. Median hospital stay for the remaining 16 cases was 16 days. 15 out of 16 cases survived with a survival rate of 93.7% and one mortality (6.2%). Conclusion: Melioidosis is a potentially fatal disease. High index of suspicion is required for diagnosing this condition due to its varied presentation. Early diagnosis and appropriate treatment is the cornerstone in improving the outcome. Though mortality was less than 6%, they have significant morbidity with prolonged ICU and hospital stay leading to increased economic burden.

A Case Report of Novel Coronavirus-2019 (COVID-19) Disease and Cytomegalovirus (CMV) Co-Infection: A Lethal Combination

Aim and background: The novel coronavirus-2019 (COVID-19) pandemic is raging all across the world. As we are delving more into the management of COVID-19, many new challenges are emerging, which may pose additional threats. One of these is the emergence or re-activation of concomitant viral infections owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation. Although we have come across the threat of fungal infections and resistant bacterial infections, experience regarding reactivation or co-infection with other viral infections is still limited. We hereby describe a case of COVID-19 disease with cytomegalovirus (CMV) co-infection. Case summary: COVID-19 with Cytomegalovirus (CMV) Co-infection. A 55-year-old male, COVID unvaccinated, chronic smoker, overweight, and hypertensive patient was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86% on room air), respiratory rate (RR) 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. A possibility of Guillain-Barre Syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction (in the form of paralytic ileus and abdominal distension). In evaluation, polymerase chain reaction (PCR) for CMV turned out to be positive in blood with a very high viral load.Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and haemophagocytosis (HLH). Histological evidence of CMV inclusion bodies was present in the bone marrow besides viremia (detected by PCR for CMV), which confirmed the diagnosis of CMV co-infection. IV ganciclovir was initiated along with steroids in view of HLH. There was a decrease in CMV viral load after initiation of IV gancyclovir with subtle clinical recovery. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

IMMUNE SYSTEM IN MOTION: A CASE OF ADULT-ONSET STILL'S DISEASE

CASE: A 23-year-old female with a history of congenital deafness and HLAB27 positivity presented for two weeks of diffuse arthralgias, fever, and nausea. She had a history of an erythematous rash around her eyes and upper chest that had resolved with prednisone;however, her other symptoms persisted. She denied known tick exposures, drug use, sick contacts, or travel, but had recently been hiking. On presentation, she was febrile to 38.8°C and tachycardic to 130 beats/min. Her labs were notable for an AST of 232 U/L, ALT of 266 U/L, LDH of 680 U/L, haptoglobin <10 mg/dL, and ferritin of 12,230 ng/mL, with no cytopenias or leukocytosis. Her CRP was 127 mg/dL and ESR was normal. Her troponin and BNP were both elevated, to 54 ng/L and 468 pg/mL respectively. ANA and RF titers was negative. Viral studies including EBV, CMV, and SARSCoV-2 as well as bacterial studies were negative. She was started on doxycycline for possible tick-borne infection, but titers returned negative. Echocardiography and chest x-ray were unremarkable. CT scan demonstrated nonspecific para-aortic and mesenteric lymphadenopathy. The patient's presentation and labs were consistent with adult-onset Still's disease (AOSD), meeting the Yamaguchi criteria for diagnosis. She was started on IV hydrocortisone and anakinra with symptomatic improvement. Her liver function testing worsened due to concerns for macrophage activation syndrome (MAS). She was treated with ruxolitinib with gradual improvement in her liver function, followed by tofacitinib. She made a full recovery on discharge. IMPACT/DISCUSSION: Due to its rarity, AOSD can be challenging to diagnose. This case highlighted the key manifestations and distinguishing characteristics of the disorder. The patient presented with fever, rash, and polyarthralgias. While the location of the rash in AOSD varies, the upper chest as seen in this case is typical. While this patient did not have cytopenia or leukocytosis, she did have elevated transaminases and a disproportionately elevated ferritin, a hallmark of AOSD. Importantly, ANA and RF titers were negative, which helps to differentiate AOSD from other autoimmune disorders. The case also demonstrated a feared complication of AOSD, MAS, a form of hemophagocytic lymphohistiocytosis that occurs in 10-15% of patients with AOSD. This case highlighted the importance of remaining vigilant for MAS, as the patient's liver function continued to decline despite symptomatic improvement. While MAS is difficult to diagnose, hyperferritinemia and pancytopenia are thought to be relatively strong indicators. CONCLUSION: AOSD is a rare and debilitating disease, with an illness script that has significant overlap with other diseases. In addition to the combination of polyarthralgias, rash, and fevers, a markedly elevated ferritin is a strong indicator of AOSD. ANA and RF titers will be negative. It is crucial to remain vigilant for complications of the disease, such as MAS.