A Computational Framework for Determining the Breadth of Antibodies Against Highly Mutable Pathogens

Highly mutable pathogens pose daunting challenges for antibody design. The usual criteria of high potency and specificity are often insufficient to design antibodies that provide long-lasting protection. This is due, in part, to the ability of the pathogen to rapidly acquire mutations that permit them to evade the designed antibodies. To overcome these limitations, design of antibodies with a larger neutralizing breadth can be pursued. Such broadly neutralizing antibodies (bnAbs) should remain targeted to a specific epitope, yet show robustness against pathogen mutability, thereby neutralizing a higher number of antigens. This is particularly important for highly mutable pathogens, like the influenza virus and the human immunodeficiency virus (HIV). The protocol describes a method for computing the "breadth” of a given antibody, an essential aspect of antibody design. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.

TB DURING THE SEROCONVERSION PHASE

SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Patients who are HIV positive have a high risk of co-infection with tuberculosis (TB). Screening tests for HIV identify antibodies that are present during the seroconversion, or window phase. Here we present a case of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON test. CASE PRESENTATION: A previously healthy 24-year-old female presented with a productive cough. She was found to have leukopenia and apical consolidation on chest CT and was treated for community-acquired pneumonia with mild improvement of symptoms. Her QuantiFERON, COVID-19, and HIV antibody screen were negative;however, her reflex HIV antigen was positive. She re-presented a month later with a worsening cough, drenching night sweats, weight loss, vomiting, and dysphonia. Her chest CT noted a right apical cavitary lesion and bilateral upper lobe micronodules with endobronchial spreading. Her QuantiFERON and HIV antibody were now both positive. She was started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy and on raltegravir and emtricitabine/tenofovir. DISCUSSION: Above we describe a case of reactivation TB during the seroconversion phase of HIV with a negative QuantiFERON. Primary TB presents in the middle lobes without signs of structural damage whereas secondary TB typically involves the apices and presents with cavitation. Secondary TB is typically due to reactivation or reinfection in immunosuppressed patients. Although we believe this case is due to reactivation due to radiographic findings, her initial QuantiFERON was negative. However, studies have shown that QuantiFERON may have uncertain results in latent TB infections in patients with underlying HIV (1). Reliable testing for latent TB in HIV-positive individuals is necessary as HIV increases the risk of developing active TB and TB increases the risk of transitioning from HIV to AIDS (2). CONCLUSIONS: TB is one of the top 10 causes of death worldwide and HIV is a common coinfection. To the best of our knowledge, this is the first published report of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON. Overall, more research must be done to identify the risk of infections during the seroconversion phase and physicians must be able to identify radiographic findings concerning for TB in patients with underlying HIV. Reference #1: Elisa Petruccioli, Teresa Chiacchio, Elisa Petruccioli, et al. Effect of HIV-infection on QuantiFERON-plus accuracy in patients with active tuberculosis and latent infection, Journal of Infection, 2020;80(5): 536-546. https://doi.org/10.1016/j.jinf.2020.02.009. Reference #2: Bruchfeld, Judith et al. "Tuberculosis and HIV Coinfection.” Cold Spring Harbor perspectives in medicine vol. 5,7 a017871. 26 Feb. 2015, doi:10.1101/cshperspect.a017871 Reference #3: Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137-2147. doi:10.1097/00002030-200111090-00009 World Health Organization. Tuberculosis [Internet]. 2021 [cited 2022 Mar. 15];Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis DISCLOSURES: No relevant relationships by Loor Alshawa No relevant relationships by Angela Binkowski No relevant relationships by Sara Qutubuddin

EXTENSIVE PNEUMATOCELES DUE TO PNEUMOCYSTIS JIROVECI PNEUMONIA IN A PATIENT NEWLY DIAGNOSED WITH HIV INFECTION

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Pneumatoceles are air-filled cavitary lesions that are rarely seen in the lung after infection, trauma, or as part of a more diffuse cystic disease process. Several infectious agents have been associated with pneumatoceles, one of them being Pneumocystis Jirovecii, a potentially life-threatening fungus commonly seen as an opportunistic infection in immunocompromised patients. We present a case of bilateral extensive pneumatocele in a newly diagnosed HIV patient found to be positive for Pneumocystis pneumonia CASE PRESENTATION: A 52-year-old female presented to the emergency room for 2 months of shortness of breath, body aches, and chills. She was saturating at 86% on room air on arrival. Initial chest x-ray showed bilateral airspace disease. Had additional history of daily smoking, polysubstance abuse, and poor follow-up with doctors’ appointments due to social issues. She was started on oxygen support, steroids, antibiotics, and IV fluids. Labs were notable for normal overall WBC count but low lymphocyte count of 0.4. A CT Angiogram of the chest showed moderate to severe diffuse bilateral gas-filled cystic structures throughout the lungs, consistent with pneumatoceles. Infectious workup performed: COVID PCR, Influenza A/B antigen, legionella antigen, strep. pneumoniae antigen, B-D-glucan assay, histoplasma and blastomyces antigens, and HIV antibody. HIV antibody, strep pneumo antigen, and B-D-glucan assay came positive. She did not have a known diagnosis of HIV prior to this admission. Antibiotic regimen was changed to ceftriaxone, azithromycin, Bactrim, and fluconazole. Bronchoscopy with lavage was performed. Lavage samples were sent for cytology and found to be positive for Pneumocystis on GMS stain HIV viral load was checked and found to be at 1.4 million copies. CD4 count was less than 25 Patient was started on antiretroviral therapy in addition to prolonged course of Bactrim. She was ultimately discharged from the hospital in stable condition with pulmonary and infectious disease follow-up. At this time her pneumatoceles have improved on follow-up imaging. DISCUSSION: Pneumatoceles can rarely present as a complication of PCP pneumonia and can be a marker of more advanced disease. In our patient, pneumatoceles were identified first followed by diagnosis of HIV and PCP pneumonia. Overall incidence of post-infectious pneumatoceles is low at 2-8%. Prompt treatment and careful monitoring is needed due to risk of mortality from underlying infection and progression to pneumothorax. CONCLUSIONS: HIV with PCP infection complicated by pneumatocele formation is much less common due to improvements in HIV detection and screening for opportunistic infection, but should remain an important consideration in patients with unexplained cystic lung disease patterns, especially in patients without established outpatient follow-up or who don't see medical providers often. Reference #1: Thomas CF Jr, Limper AH: Pneumocystis pneumonia. N Engl J Med. 2004;350: pp. 2487-2498. Reference #2: Albitar, Hasan and Saleh, Omar M. Pneumocystis Pneumonia Complicated by Extensive Diffuse Pneumatoceles. Am J Med. 2019 May;132(5):e562-e563. Epub 2019 Jan 16. Reference #3: Ryu, Jay et al. Diffuse Cystic Lung Diseases. Frontiers of Medicine volume 7, pages 316–327 (2013) DISCLOSURES: No relevant relationships by Clifford Hecht

DISSEMINATED HISTOPLASMOSIS IN THE SETTING OF IMMUNOSUPPRESSION DUE TO CROHN DISEASE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber

A LESSON ON ANCHORING BIAS DURING A PANDEMIC: A CASE PRESENTATION

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Anchoring bias is a cognitive bias where one relies too heavily on initial information early on in the decision making process, affecting subsequent decisions due to future arguments being discussed in relation to the "anchor. Overemphasis on COVID-19 due to the pandemic has impacted the timely diagnosis and treatment of other diseases. CASE PRESENTATION: A 39-year-old man with a past medical history of COVID 19 in 12/2020 presents to the ED with increasing weakness, chest pain, recurrent fevers, diarrhea, and cough. CXR revealed bilateral infiltrates suggestive of pneumonia/pulmonary edema. Patient was empirically started on ceftriaxone. CT chest was suspicious of COVID-19;however repeat testing was negative. Diarrhea did not improve. Patient later admitted to recent travel to Jamaica. Ova and parasite, C-difficile, and stool culture were negative. On hospital day 8, the patient was intubated and placed on mechanical ventilation for worsening hypoxic respiratory failure Infectious disease was consulted for recurrent fevers of unknown origin and diarrhea with recent travel. Testing for typhoid fever, hantavirus, malaria, HIV, zika virus, chikungunya, dengue, and yellow fever were performed. Consent was obtained for HIV testing. HIV antibody tests were positive, CD4 count of 7, and viral load greater than 900k. Since a new diagnosis of AIDS with a CD4 count of 7 was obtained, the patient was subsequently tested for opportunistic infections such as TB. TB sputum PCR testing was positive but AFB smear was negative for TB. Antiretroviral and tuberculosis treatments were initiated. DISCUSSION: Anchoring bias can delay critical diagnoses and impede patient care if it is not recognized. According to Watson et. al, one way physicians circumvent the thought of pretest probability when ordering tests based on patient history and the subsequent list of differential diagnoses is anchoring bias. Bypassing the pretest probability also alters the sensitivity and specificity of testing because results that do not confirm or rule out a top differential diagnosis are thought to be inaccurate and are then repeated attributing the initial result to a bad specimen or an improper collection of the specimen. CONCLUSIONS: The case presented exemplifies clearly the concept of anchoring bias. Upon initial presentation, the patient had nonspecific symptoms such as weakness, chest pain, recurrent fevers, diarrhea, and cough, all of which can be symptoms of COVID 19 in the setting of a global pandemic. It is clear that the initial diagnosis based on these symptoms was COVID 19. When initial testing was negative, anchoring bias still played a role in the decision to test the patient once again, despite the first negative test. Repeat testing still did not support the diagnosis of COVID 19, which expanded the differential diagnosis and ultimately led to the correct diagnosis of AIDS with concomitant TB infection. Reference #1: Saposnik, et. Al. Cognitive Biases Associated with Medical Decisions: A Systematic Review. BMC Med Inform Decis Mak. 2016 Nov. 3. PMID: 27809908 Reference #2: Harada, et. al. COVID Blindness: Delayed Diagnosis of Aseptic Meningitis in the COVID-19 Era. Eur J Case Rep Intern Med. 2020 Oct 23. PMID: 33194872. Reference #3: Singh, et. al. The Global Burden of Diagnostic Errors in Primary Care. BMJ Qual Saf. 2016 Aug 16. PMID: 27530239. DISCLOSURES: No relevant relationships by Sagar Bhula

A UNIQUE CASE OF CANDIDA RETINITIS IN THE COVID-19 ERA

CASE: A 56-year-old male with a history of asthma was admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure. He was found to have sepsis secondary to pneumococcal pneumonia superinfected by COVID19. Labs showed elevated inflammatory markers. Chest x-ray initially demonstrated left lower lobe pneumonia but throughout the COVID-19 course, worsened to persistent multifocal pneumonia. The patient was intubated and treated with enoxaparin and a ten-day course of dexamethasone as well as antibiotics due to worsening clinical status. After the COVID-19 course resolved and the patient was extubated, he developed sepsis again - this time secondary to Candidemia. Treatment with intravenous micafungin was initiated and HIV antibodies screening returned negative. The patient began to report subacute visual changes including floating spots and blurry vision in the right eye without any other acute ocular symptoms. Upon ophthalmological exam, there were multiple white retinal lesions without vitreous involvement bilaterally on the macula indicating candida retinitis. Antifungal treatment with micafungin was changed to intravenous voriconazole for greater intraocular penetration. After seven days of intravenous voriconazole, two blood cultures came back negative for Candida. At this point, the patient was medically stable and was discharged on a six- week course of oral voriconazole. IMPACT/DISCUSSION: The COVID-19 pandemic changed the landscape of medicine. Not only have healthcare systems worked hard to treat the COVID-19 infections themselves but also the long-term effects that result from an infection. As treatment guidelines have been developed and honed, steroids appear at the forefront of therapy. However, this does not come without consequences as prolonged use of corticosteroids can dampen the body's immune system. This compounds the ability of COVID-19 pneumonia to result in a severely immunocompromised state that can subsequently expose the body to opportunistic infections. Candida albicans is an organism that exists in all humans in the gastrointestinal and genitourinary systems typically without impact. In severely immunocompromised individuals such as the patient in the case, hospital courses involving ICU care can lead to hematogenous spread of Candida. The candidemia leads to sepsis and may also present with rare clinical pictures such as Candida retinitis. For this reason, candidemia should prompt thorough evaluation of patients with an echocardiogram, abdominal computer tomography, and ophthalmologic exam. CONCLUSION: This case displays the ability of COVID-19 infections to provide an opportunity for rare infectious manifestations such as Candida retinitis. As the pandemic prolongs, proper treatment regimens must be reassessed for future use as these presentations may become more common.

CRIVALVIR-FOCUS: low HIV and chronic Hepatitis B and C infection prevalence among women in reproductive and sexual health services in Valencia, Spain

Background and Aims: In Spain, HIV, HBV, and HCV prevalence are lower in females. A 2017–2018 Ministry of Health serosurvey in 7, 675 primary care patients found 0.35% and 0.08% chronic HCV infection in men and women. A previous opportunistic, population-based screening program in 11, 449 primary care patients seen in our health department found 0.18% and 0.06% HIV infection prevalence, 1.11% and 0.56% chronic HBV infection prevalence, and 0.73% and 0.25% chronic HCV infection prevalence in men and women from February to December 2019. We aimed to assess HIV, HBV, and HCV prevalence among women seeking care in our health department’s 5 Sexual and Reproductive Health Units (SRHU), in the Human Reproduction Unit (HRU), and the Obstetrics and Gynecology Service (OGS). Method: We implemented opportunistic HIV, HBV, and HCV screening from March to October 2021, despite challenges related to a fifth wave of the SARS-CoV-2 pandemic. We used existing infrastructure and staff, aided by electronic health record system modifications, to identify screening eligibility and request serologies. Patients were eligible for testing upon verbal consent if they were between 18 and 80, and had no record of testing in the previous year, and required blood tests in their current health care visit. Follow-up or discharge was given, regardless of test results. A case manager contacted positive patients to ensure and monitor linkage to specialist medical care. Herein we analyze data from patients aged 18 to 45 — the maximum age of patients seen in the HRU. Results: We screened 934 women, of whom 48.1% (449) in SRHUs, 26.0% (243) in the HRU, and 25.9% (242) in the OGS (26%). Regarding age and nationality,14.6.% (136)were aged 18 to 25, 45.5% (425)were 26 to 35, 39.9% (373) were 36 to 45, and 20.6% (192) were foreigners. We found 1 (0.1%) HIV antibody positive patient (a 45-year-old from the Dominican Republic), 1 (0.1%) HBV surface antigen positive patient (a 36-year-old from China), 1 (0.1%) HCV antibody positive patient, and no HCV RNA positive patients. Conclusion: HIV prevalence among Valencian women in reproductive and sexual health serviceswas similar to the general population in primary health care in the area. In contrast, chronic HBV infection prevalence was low, and chronic HCV infection was not found. Our data suggest that opportunistic HBV and HCV screening of women aged 18 to 45 out of populations at increased risk is an inefficient public health strategy in our area

A Case of an 83 Year Old Male with Acute Disseminated Encephalomyelitis-like Presentation Post COVID-19 Vaccination

Objective: NA Background: A variety of neurologic disorders have been described in patients after receiving the COVID-19 vaccines. Acute disseminated encephalomyelitis (ADEM) have been reported especially in the younger population following any vaccination, including the Covid-19 vaccines. Reports of ADEM in the elderly patients are scarce. Design/Methods: An 83 year old male with history of hypertension, presented with suddenonset of progressive multifocal neurological deficits including blurry vision, upper extremity weakness, numbness and clumsiness with imbalance resulting in multiple falls. A few days later, he reported dysphagia, intermittent expressive aphasia and confusion. Thirteen days prior, he received his second dose of Moderna vaccine. Examination showed mild bilateral upper motor neuron and cerebellar signs. Laboratory tests were unremarkable except for elevated ESR (72), low Vitamins-B12 (311 pg/mL), and D (14.9 ng/mL) levels, and iron deficiency anemia. MRI brain with gadolinium revealed non-enhancing multifocal and confluent supra/infratentorial T2/FLAIR hyperintensity lesions. Cerebrospinal fluid (CSF) analysis showed pleocytosis (whitecell count 13 with 60% lymphocytes), elevated protein (54), and glucose (80), suggestive of underlying inflammation. CSF cytology, meningoencephalitis panel, VDRL, JC-virus PCR, India-ink, acid-fast, bacterial and fungus cultures were negative. HIV antibody was negative. Intravenous Ceftriaxone was initiated until CSF cultures returned negative. Serum anti-MOG and anti-NMO were negative. Repeat imaging within a week showed decreased confluent T2 hyperintensities, but also demonstrated new areas of patchy involvement. The patient received intravenous methylprednisolone 1000 mg daily for 5 days. In the following weeks, his symptoms improved remarkably. Results: NA Conclusions: This 83 year old patient presented with multiple neurologic symptoms, confluent T2-Flair white matter hyperintensities on imaging studies, 13 days post Covid-19 vaccination. Workup for other inflammatory and infectious etiologies was unrevealing. Symptoms improved after intravenous corticosteroids treatment. ADEM is a consideration. Theoretical and actual concerns of vaccine-related neurologic diseases exist, timely recognition and treatment can alter the course and disease progression.