Comparison of Diagnostic Accuracy of CRP Versus Ferritin in COVID Patients as a Marker of Severity of Disease Taking who Severity Classification as Gold Standard

Objective: To determine the diagnostic accuracy of elevated C reactive protein (CRP) and ferritin in predicting severe Covid-19 infection using the World Health Organization's (WHO) Covid-19 severity classification as gold standard. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at the Pak Emirates Military Hospital, Rawalpindi, from January 1st 2021 till April 30th 2021. Ethical review committee's (ERC) approval was taken and good clinical practice guidelines were followed. Material(s) and Method(s): Baseline blood samples were sent to the hospital laboratory for the measurement of C reactive protein and ferritin levels. PCR was taken as gold standard for the diagnosis of Corona virus disease. Patients were classified into severe and non-severe categories using WHO classification of severity. Sensitivity, specificity, diagnostic accuracy, negative predictive value and positive predictive value were calculated for elevated CRP and ferritin. Result(s): There were 65 (57.5%) patients who had severe Covid-19 disease and 48 (42.5%) patients who had non-severe Covid-19 disease. Among the patients with severe Covid-19, 57 (87.7%) had elevated CRP levels, and 50 (76.9%) patients had elevated ferritin levels. Testing ferritin levels, against the severity of Covid-19 patients, there was a sensitivity of 76.9%, specificity of 79.2%, positive predictive value (PPV) of 83.3%, negative predictive value (NPV) of 71.7% and diagnostic accuracy of 77.8%. Testing CRP levels, there was a sensitivity of 87.7%, specificity of 85.4%, PPV of 89.1%, NPV of 83.6% and diagnostic accuracy of 86.7%. Conclusion(s): The results from our study show that CRP has a slightly improved diagnostic accuracy as compared to ferritin. However, both these markers have value in the prediction of severity of Covid-19 infection.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

THE ERA OF HIV-NEGATIVE PNEUMOCYSTIS PNEUMONIA

SESSION TITLE: Chest Infections in Immunocompromised Patients Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection caused by Pneumocystis jirovecii. HIV-negative patients with PCP are primarily individuals receiving immunosuppressive therapy for other disease processes. In rare instances, PCP could be an initial manifestation of underlying defected or suppressed cell-mediated immunity that needs to be diagnosed to prevent morbidity and mortality. CASE PRESENTATION: 75-year-old female with a history of hypertension and hypothyroidism presented to the emergency department for evaluation of cough, fever, and shortness of breath gradually worsening over the last few weeks. She received outpatient treatment with no improvement. She was vaccinated against covid-19. On presentation, the temperature was 103F, heart rate was 108 bpm, blood pressure was 163/93 mm Hg, and oxygen saturation was 86% on room air. Hemogram showed leukocytosis with left shift with elevated inflammatory markers. Chest X-ray revealed bilateral ground glass opacities. She was started on broad-spectrum antibiotics, but symptoms worsened over the next few days. CT chest showed diffuse bilateral ground glass opacities with prominent interstitial markings. BAL obtained from bilateral upper lobes was lymphocyte predominant with pneumocystis jirovecii diagnosed on Gomori methenamine silver (GMS) staining. She was started on PCP-directed antibiotics with intravenous glucocorticoids, and workup for an underlying immunodeficiency was started. Subsequent BATS biopsy revealed diffuse organizing alveolar damage, with possible associated acute interstitial pneumonia pattern. This could be a rare manifestation of PCP or a primary presentation in the appropriate clinical setting. Autoimmune panel, leukemia, and lymphoma panel came back negative. AFB smear, HIV, EBV, CMV, HTLV I/II also returned negative. The lymphocyte subset panel revealed a CD4 count of 205 and a subsequent count a few days later of 64 with decreased total IgG. The patient was treated with high dose steroids for an extended period along with treatment for PCP however continued to decline clinically. The patient and family eventually decided to pursue comfort care. DISCUSSION: The predisposition to PCP in patients is primarily due to a decrease in cell-mediated immunity regardless of HIV infection. In our patient, the etiology of idiopathic CD4+ T cell lymphocytopenia cannot be determined due to the lack of serial laboratory data measurement. One of the proposed etiologies of ICL is systemic persistent immune activation in the setting of exogenous mRNA, the current technology that is being widely used for vaccine development. CONCLUSIONS: In this era of biotechnology, with advancements in immunosuppressive therapy and mRNA-based vaccines, increased awareness around the potential immune system activation and potential downstream complications needs to be further highlighted to raise awareness among physicians. Reference #1: Li, Y., Ghannoum, M., Deng, C., Gao, Y., Zhu, H., Yu, X., & Lavergne, V. (2017). Pneumocystis pneumonia in patients with inflammatory or autoimmune diseases: usefulness of lymphocyte subtyping. International Journal of Infectious Diseases, 57, 108-115. Reference #2: Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines - a new era in vaccinology. Nature reviews. Drug discovery, 17(4), 261–279. https://doi.org/10.1038/nrd.2017.243 Reference #3: Vijayakumar, S., Viswanathan, S., & Aghoram, R. (2020). Idiopathic CD4 Lymphocytopenia: Current Insights. ImmunoTargets and therapy, 9, 79–93. https://doi.org/10.2147/ITT.S214139 DISCLOSURES: No relevant relationships by Santhosh Gheevarghese John No relevant relationships by Konstantin Golubykh No relevant relationships by Iuliia Kovalenko No relevant relationships by Maidah Malik No relevant relationships by Hafiz Muhammad Siddique Qurashi No relevant relationships by Taj Rahman No rel vant relationships by Tabinda Saleem

ATYPICAL PAROTITIS AS A RESULT OF SEVERE COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Parotitis occurs in extremes of age and is associated with infections or inflammatory conditions. Typical bacterial parotitis presents with a unilateral, tender enlarged parotid gland and fever whereas inflammatory parotitis presents with bilateral enlargement of the parotids without fever. Here, we present two atypical cases: bilateral parotitis likely secondary to bacterial infection and unilateral parotitis likely due to inflammation. CASE PRESENTATION: We present a 45-year-old male with history of obesity who presented with hypoxia and dyspnea. CT angiogram noted multifocal pneumonia, consistent with COVID-19. He was started on dexamethasone, remdesivir and baricitinib as well as community acquired pneumonia coverage. On day 5, he was placed on high-flow nasal cannula due to progressive hypoxia. Although initially afebrile, he developed a fever on day 12, with tachypnea and tachycardia. Acute swelling of the submandibular space with adjacent erythema and a lactic acid of 3.2 were noted. CT neck demonstrated enlarged parotid glands bilaterally with inflammatory changes indicative of parotitis, no abscess or mass was noted. He was started on vancomycin, with improvement of his erythema and swelling within 3 days. Blood cultures were positive for MSSA. Patient continued to deteriorate, requiring intubation on day 18 and died on day 34.The second case is a 79-year-old-male with history of COPD on 3L and type 2 diabetes mellitus who presented with hypercapnic respiratory failure, found to be COVID-19 positive. The patient required non-invasive ventilation for progressive respiratory failure, despite COVID-19 treatment. He developed a sudden swelling of the right mandibular area on day 7 of admission. CT neck identified an enlarged heterogenous enhancement of the right parotid gland and edema consistent with parotitis. Blood cultures were negative. The patient was started on vancomycin but had worsening oxygen requirements and encephalopathy, was ultimately made DNR and expired on day 9. DISCUSSION: There has been increased incidence of atypical disease presentation and reactivation of latent infections during the COVID-19 pandemic. In the above patients, parotitis occurred secondary to severe viral illness, immune suppression, increased inflammation and/or superimposed bacterial infection. COVID-19 has been shown to cause significant inflammatory response and immunosuppression with lymphopenia, thrombocytopenia and low complement levels. Both patients had elevated inflammatory markers and persistent leukopenia. CONCLUSIONS: The pathophysiology of atypical parotitis and other atypical disease presentations, in the setting of severe COVID-19, should further be investigated. REFERENCE #1: Tian W, Zhang N, Jin R, et al. Immune suppression in the early stage of COVID-19 disease. Nat Commun. 2020;11(1):5859. Published 2020 Nov 17. doi:10.1038/s41467-020-19706-9 REFERENCE #2: Fisher J, Monette DL, Patel KR, Kelley BP, Kennedy M. COVID-19 associated parotitis. Am J Emerg Med. 2021;39:254.e1-254.e3. doi:10.1016/j.ajem.2020.06.059 REFERENCE #3: Wilson M, Pandey S. Parotitis. [Updated 2020 Dec 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560735/ DISCLOSURES: No relevant relationships by Michael Bonk, source=Web Response No relevant relationships by Andrew Marcano, source=Web Response No relevant relationships by Ananya Nanduri, source=Web Response No relevant relationships by TAHMINA SALEEM, source=Web Response

COVID-19 COAGULOPATHY SECONDARY TO ACTIVATING PLATELET ANTIBODIES

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coagulopathies have been extensively reported in COVID-19 patients (1). CASE PRESENTATION: A 58-year old female presented to the emergency department (ED) with 2-weeks history of shortness of breath. A nasopharyngeal swab was positive for SARS-CoV-2. She was treated and discharged on room air. D-dimer (DD) and platelet (plt) count at the time of discharge were within normal. Six days after discharge she presented to the ED with severe abdominal and right leg pain. Lower extremity pulses were present by doppler but hard to palpate. Laboratory tests showed elevated DD (27,820 ng/ml) and elevated plt (530 x109/L), table-1. Computed tomography scan (fig-1) of the abdomen and pelvis showed multiple wedge-shape infarcts in the liver, spleen, and right kidney and acute thrombosis of the right common iliac artery. Acute deep vein thrombosis in the lower and upper extremities were excluded by US. Duplex US of the right lower extremity showed ankle brachial index of 0.2. The patient was admitted and started on heparin therapy. On day 2, plt count dropped to 127 x 109/L. The 4T score was 5, heparin was stopped and argatroban was started. Serotonin release assay was sent and showed no inhibition with high dose heparin. However, non-heparin dependent anti-platelet activating antibodies (class I HLA antibodies) were detected. Anti-platelet factor-4 was negative and patient was restarted back on heparin. Thrombophilia and autoimmune work up were negative. Patient was discharged on low-molecular weight heparin. Plt count was 179 x109/L before discharge. DISCUSSION: Recent study published by Bilaloglu showed that 533 (16.0%) COVID-19 patients had at least one thrombotic evet during hospitalization. Of all 3334 patients, only 32 (1.0%) had acute limb ischemia, upper extremity arterial thrombosis, renal, and splenic infarcts, and portal vein thrombosis (2). In another case series, 4 of the reported 7 cases developed progressive irreversible lower limb ischemia. Two patients presented with lower limb ischemia and the other two developed severe thrombosis after 4 and 15 days respectively. Of the reported lab values, two patients had D-dimer levels more than 20,000 ng/ml and the same two were thrombocytopenic (1). Interestingly, our patient had reversible limb ischemia as shown by the repeated duplex US done after discharge. Nicolai and colleagues reported that plts hyperactivation and possible immuno-thrombosis may play a role in the pathogenesis of coagulopathy among severe COVID-19 patients (3). In our case, patient had hypercoagulability secondary to activating anti-platelets antibodies, a novel finding that can help understanding the pathogenesis of COVID-19 induced hypercoagulability. CONCLUSIONS: COVID-19 associated coagulopathy can be un-predictable. Activating anti-plt antibodies may play a role in the pathogenesis of COVID-19 coagulopathy. REFERENCE #1: Kashi M, Jacquin A, Dakhil B, et al. Severe arterial thrombosis associated with Covid-19 infection. Thromb Res 2020;192:75-7. REFERENCE #2: Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA 2020. REFERENCE #3: Nicolai L, Leunig A, Brambs S, et al. Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy. Circulation 2020. DISCLOSURES: No relevant relationships by Bahaa Abdelghaffar, source=Web Response No relevant relationships by hamed daw, source=Web Response No relevant relationships by Tariq Kewan, source=Web Response No relevant relationships by Talha Saleem, source=Web Response

Bispecific CART cells in the treatment of relapsed and refractory multiple myeloma: A review of literature

Background: Chimeric antigen receptor T cells (CART) have shown promising results in the treatment of relapsed and refractory multiple myeloma (RRMM). Recently, bispecific-CART cells targeting 2 antigens are being evaluated in various clinical trials. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Data presented at annual hematology and oncology conferences were also included. Results: We included 4 phase I clinical trials with a total of 77 RRMM patients between the ages of 18 to 71 years. The median follow-up duration ranged from 1 month to 27.5 months. All were lymphodepleted with Cyclophosphamide and Fludarabine before receiving CAR-T cell therapy. The CAR-T cell targets include BCMA and CD38 (dose range 0.5 x 10∧6 - 4 x 10∧6 cells/kg), BCMA and TACI (dose range 15 - 900 x 10e6 CAR-T cells), BCMA and CD19 (1 x 10e5/kg - 3 x 10e5 CAR-T cells/kg), and BCMA and CD19 (dose 1 x 10e6 cells/kg). Overall response rate (ORR) was reported by 4 trials (87.5%, 43%, 93.8%, 95%). Complete response (CR) was also reported in 4 trials as 50%, 64%, 56.3% and 14% and partial response (PR) reported as 25%, 28%, 16.6%, 14%, 18% in 5 trials (table). The most common grade 3-4 adverse effects that were reported include cytokine release syndrome, neurotoxicity, neutropenia, lymphopenia, anemia, thrombocytopenia, diarrhea, increased LDH, lower respiratory tract infections (LRTI), dehydration, renal failure (table). Yan et al. reported one death due to cerebral hemorrhage which was considered unrelated to treatment. Jiang et al. reported one death from unknown cause of a patient who presented with fever during the COVID- 19 pandemic.Conclusions: Bispecific CART cells have shown promising results in the treatment of RRMM. However, the clinical trials are ongoing, and a longer follow-up is needed.

461 A review of cutaneous lymphoma outcomes during COVID-19 pandemic at Columbia University

New York-Presbyterian Hospital and Columbia University Irving Medical Center were heavily impacted by the COVID-19 pandemic. Various measures were taken in an effort to ensure patient and staff safety. The management of patients with complex dermatological oncologic conditions, such as cutaneous lymphomas was especially challenging. We retrospectively reviewed the charts of the patients with cutaneous lymphomas who had COVID-19 (n=7) as well as those who did not have COVID-19 (n=26) from March to September 2020. Due to safety protocols, 4/7 (57%) patients who contracted COVID-19 experienced a treatment interruption. Three patients had no treatment interruptions because the timing of their COVID-related illness and scheduled treatments did not overlap. Treatment was delayed for a mean 2.1 months (range: 10 days - 4 months). Two out of four (50%) patients with treatment delays experienced disease relapse. Of the patients who did not have COVID-19, 12 patients experienced treatment delays, and ten (83.3%) of those patients experienced disease progression or relapse. Fourteen patients continued in hospital treatments with no delay, and 2 (14.3%) patients experienced disease progression or relapse. Of the total patients included in this review, 16 (48.5%) experienced a treatment. Delay. Twelve patients (12/16 or 75%) had disease relapse or progression following treatment delays. In contrast, among the 17 patients who did not experience treatment delay, 4 (23.5%) patients had relapse or progression of disease. Treatment delay was associated with a significant risk of disease relapse or progression (p=0.0053). No hospital-related cases of COVID-19 were recorded during the six-month capture period. Treatment interruptions are associated with negative clinical outcomes. Established safety protocols are effective in preventing infections during therapy for cutaneous lymphomas. We do not recommend altering treatment regimens for patients with cutaneous lymphomas if safety protocols can be assured.

SUPERINFECTIONS IN PATIENTS INFECTED WITH COVID-19: A SINGLE-CENTER EXPERIENCE

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Bacterial and fungal infections in COVID-19 patients have been inadequately studied and reported. The purpose of this study is to determine the incidence and outcomes of superinfections in patients with COVID-19. METHODS: A retrospective observational study of all patients diagnosed with COVID-19 at Fairview Hospital-Cleveland Clinic. Main outcomes were incidence of bacterial, viral and fungal infections among COVID-19 patients and in-hospital mortality. RESULTS: There were 82 patients diagnosed with COVID-19. Fifty-one (62.2%) were male and median age was 64.5 years. On admission, 48 (58.5%) patients were admitted to ICU and 13 (15.9%) required mechanical ventilation. Of all patients, 22 (26.8%) developed superinfection during admission. Only three had positive PCR for other viruses;two had respiratory syncytial virus and one had influenza A. Methicillin resistant staphylococcus aureus (MRSA) was detected in 5 (6.1%) patients. Superimposed bacterial pneumonia were detected in 13 (12.2%) patients;2 MRSA, 2 methicillin sensitive staphylococcus aureus, 2 Corynebacterium striatum, 2 pseudomonas aeruginosa, 2 mycoplasma pneumoniae, 1 legionella, 1 serratia marcescens and 1 klebsiella pneumoniae. Only one patient had aspergillus fumigatus lung infection. Positive blood cultures were detected in 4 (4.9%) patients and included a case of candidemia. Urinary tract infection was diagnosed in 10 (72%) patients, and only 2 had a foley’s catheter. Corticosteroids were used in the treatment of 37 (45.1%) patients, with only 8 of the 22 patients who developed superinfections. Compared to the no superinfection cohort, patients who developed superinfection were more likely to require ICU admission (77.3% vs 53.3%, p 0.05), develop circulatory shock (59.1% vs 30.0%, p 0.016), require mechanical ventilation (63.6% vs 33.3%, p 0.014) and had lower median absolute lymphocytes count (1455/mm3 vs 5700/mm3, p 0.006). In multivariate analysis, circulatory shock (p 0.046) and need for mechanical ventilation (p 0.037) remained significantly associated with superinfection. Median time to superinfection development was 5 days with an overall mortality of 19.5%. The mean overall survival time among patients who developed superinfections was not significantly different compared to no superinfection group, 53.5 days (95% CI: 46.7-60.3) and 48.5 days (95% CI: 42.6-54.5) respectively, (p 0.278). CONCLUSIONS: In our COVID-19 cohort the rate of superinfection was 26.8%. Superinfection was associated with higher rates of circulatory shock and mechanical ventilation. The use of corticosteroids was not associated with higher rates of infections. CLINICAL IMPLICATIONS: This study will help in identifying frequent infections among COVID-19 patients in an attempt to predict and treat superinfections early in the course of the disease. DISCLOSURES: No relevant relationships by Saira Afzal, source=Web Response No relevant relationships by Sura Alqaisi, source=Web Response No relevant relationships by Sanchit Chawla, source=Web Response No relevant relationships by Tariq Kewan, source=Web Response No relevant relationships by Aisha Saand, source=Web Response No relevant relationships by Talha Saleem, source=Web Response