Immunocompromised Patient Population Research Articles

COVID-19 Vaccination Recommendations for Immunocompromised Patient Populations: Delphi Panel and Consensus Statement Generation in the United States.

The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US. A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements. Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%-96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%-69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups. Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

Potential antifungal applications of heterometallic silica nanohybrids: A synergistic activity

An estimated 1.7 million fatalities and 150 million cases worldwide are attributed to fungal infections annually, that are in rise due to immunocompromised patient population. The challenges posed by traditional treatments can be addressed with the help of nanotechnology advancements. In this study, Co, Cu, and Ag—were doped into silica nanoparticles. Then the synthesized monometallic silica nanohybrids were combined to formulate heterometallic silica nanohybrids, characterized structurally and morphologically, compared, and evaluated for antifungal activity based on their individual and synergistic activity. The antifungal assays were conducted by using ATCC cultures of Candida albicans and QC samples of Trichophyton rubrum, Microsporum gypseum, and Aspergillus niger. The MIC (ranging from 49.00 to 1560.00 μg/mL), MFC (ranging from 197.00 to 3125.00 μg/mL), IC50 values (ranging from 31.10 to 400.80 μg/mL), and FICI of nanohybrids were determined and compared. Moreover, well diffusion assay was performed. ABTS assay and DPPH assay were conducted to investigate the radical scavenging activity (RSA) of nanohybrids. SEM analysis clearly evidenced the structural deformations of each fungal cells and spores due to the treatment with trimetallic nanohybrid. According to the results, the trimetallic silica nanohybrids exhibited the most powerful synergistic RSA and the most effective antifungal activity, compared to the bimetallic silica nanohybrids.

Human Herpes Virus-6 (HHV-6) Reactivation after Hematopoietic Cell Transplant and Chimeric Antigen Receptor (CAR)- T Cell Therapy: A Shifting Landscape.

HHV-6B reactivation affects approximately half of all allogeneic hematopoietic cell transplant (HCT) recipients. HHV-6B is the most frequent infectious cause of encephalitis following HCT and is associated with pleiotropic manifestations in this setting, including graft-versus-host disease, myelosuppression, pneumonitis, and CMV reactivation, although the causal link is not always clear. When the virus inserts its genome in chromosomes of germ cells, the chromosomally integrated form (ciHHV6) is inherited by offspring. The condition of ciHHV6 is characterized by the persistent detection of HHV-6 DNA, often confounding diagnosis of reactivation and disease-this has also been associated with adverse outcomes. Recent changes in clinical practice in the field of cellular therapies, including a wider use of post-HCT cyclophosphamide, the advent of letermovir for CMV prophylaxis, and the rapid expansion of novel cellular therapies require contemporary epidemiological studies to determine the pathogenic role and spectrum of disease of HHV-6B in the current era. Research into the epidemiology and clinical significance of HHV-6B in chimeric antigen receptor T cell (CAR-T cell) therapy recipients is in its infancy. No controlled trials have determined the optimal treatment for HHV-6B. Treatment is reserved for end-organ disease, and the choice of antiviral agent is influenced by expected toxicities. Virus-specific T cells may provide a novel, less toxic therapeutic modality but is more logistically challenging. Preventive strategies are hindered by the high toxicity of current antivirals. Ongoing study is needed to keep up with the evolving epidemiology and impact of HHV-6 in diverse and expanding immunocompromised patient populations.

Patient perspectives on cancer care during COVID-19: A qualitative study.

The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time. We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022. Interviews from fifteen participants were analyzed. Two major themes emerged including COVID Impact on Care, and COVID Impact on Mental Health. Subthemes under COVID Impact on Care include Staffing Shortages, Hospital Regulations, Visitation, Importance of Advocacy, and Telehealth Utilization, and subthemes under COVID Impact on Mental Health include Loneliness, Support Networks, and Perceptions of COVID and Personal Protection. Overall, participants described positive care experiences despite notable delays, disruptions to continuity of care, difficult transitions to telemedicine, visitation policies that limited patient support, increased mental health struggles related to social distancing measures, and greater desire for patient advocacy. Our findings reveal significant impacts of the COVID-19 pandemic on experiences of cancer treatment and survivorship in a more vulnerable, rural patient population with lower healthcare access and income level. Our findings suggest areas for targeted interventions to limit disruptions to quality care in future public health emergencies.

Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys

Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. The P4J15 mAb shows <20ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.

The burden of COVID-19 in a heterogeneous population of immunocompromised patients - realities of the postpandemic

On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies.

Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term "on-target off-tumor" effects. All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion. Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination. Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. 4 Laryngoscope, 134:1642-1647, 2024.

Burkholderia vietnamiensis causing bacteremia in patients suffering from B-cell acute lymphocytic leukemia: A case series and review of literature

Burkholderia cepacia complex consists of 24 species of microorganisms that include B. cepacia, B. multivorans, B. cenocepacia, B. vietnamiensis, B. ambifaria, and many more. It is a ubiquitous microorganism found in the soil and aquatic milieu. The probability of infections in immunocompetent individuals is rare, but an increase in the population of immunocompromised patients in the past decade has attributed to increasing incidence of infections caused by these microorganisms. The most common infections caused by these isolates include bacteremia, pneumonia, genital tract infections, and surgical wound infections. Their potential to cause nosocomial outbreaks in wards of immunocompromised patients is well known. In this case series, we describe three cases of community-acquired Burkholderia vietnamiensis bacteremia in patients suffering from B-cell acute lymphocytic leukemia and their antibiotic sensitivity pattern to guide the treatment of these individuals.

Approach to patient reported outcome measures selection and implementation in a chronic norovirus clinical efficacy trial for patients after solid organ transplant.

Norovirus is the second most common cause of diarrhea among solid organ transplant recipients. There are currently no approved therapies for Norovirus, which can substantially impact quality of life, particularly in an immunocompromised patient population. In order to establish clinical efficacy and support any medication claims related to a patient's symptoms or function, the Food and Drug Administration requires that a trial's primary endpoints be derived from patient reported outcome measures- an outcome that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else. In this paper, we describe our study team's approach to the definition, selection, measurement and evaluation of patient reported outcome measures as part of establishing clinical efficacy of Nitazoxanide for acute and chronic Norovirus in solid organ transplant recipients. We specifically describe our approach to measuring the primary efficacy endpoint- days to cessation of vomiting and diarrhea after randomization through 160 days, measured through daily symptom diaries as well as the impact of treatment on exploratory efficacy endpoints, particularly change in the impact of norovirus on psychological function and quality of life.

Performance of Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening for Ruling Out MRSA Pneumonia in Hospitalized, Immunocompromised Patients.

Background: Recent literature demonstrates support for using methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (NaPCR) screening as an antimicrobial stewardship tool aiding early de-escalation of anti-MRSA antimicrobials. However, immunocompromised patients have been underrepresented in previous studies despite increased risk of morbidity and mortality from multidrug-resistant organisms (MDRO). Objective: The purpose of this study was to determine the negative predictive value (NPV) of the MRSA NaPCR in hospitalized, immunocompromised adult patients with suspected pneumonia. Methods: A single-center, retrospective, observational review was conducted of hospitalized, immunocompromised adult patients that had an MRSA NaPCR obtained between March 1, 2020 and January 10, 2021. For inclusion, bacterial cultures must have been collected within 2 weeks after MRSA NaPCR. The primary outcome was the NPV of MRSA NaPCR in hospitalized, immunocompromised patients with suspected pneumonia. Secondary outcomes include NPV in other infections. Results: Between March 1, 2020 and January 10, 2021, 59 patients with 78 unique cultures, including 28 respiratory cultures, were included in the study. The NPV of the MRSA NaPCR for pneumonia was 91.7%. The NPV for bloodstream infections was 100% and for urinary tract infections was 100%, but interpretation of these results should be cautioned due to the small sample sizes. Conclusion: The NPV of MRSA NaPCR in pneumonia remains high in this study. The MRSA NaPCR has utility as a de-escalation tool in hospitalized, immunocompromised adult patients, but larger studies are warranted to evaluate all immunocompromised patient populations.

Increasing COVID-19 vaccine adherence within an immunocompromised patient population in a community practice.

e18714 Background: Patients receiving antineoplastic therapy are at increased risk of severe illness and death from COVID-19. Vaccination against COVID-19 is an effective strategy to prevent serious complications of the disease. Because immunocompromised patients may have a blunted immune response to COVID-19 vaccinations, the CDC recommends these patients receive an additional vaccine dose. CDC recommendations serve as a guideline for optimal care of hematology/oncology patients, and within which we demonstrate a quality improvement project to promote community education and assess vaccination rates. Methods: Through Epic electronic medical record (EMR) reporting, we identified 250 immunocompromised patients who had not completed their primary COVID-19 vaccination series or booster and initiated antineoplastic therapy between 12/1/2020- 12/1/2021 at a community-based oncology practice in Michigan. Patients were provided an electronic patient portal letter detailing vaccination recommendations, information on how to obtain vaccination, and a survey inquiring if patients were more likely to become vaccinated after the educational intervention. 204 patients received electronic letters and 46 patients (without portal access) were sent a letter via the US postal service. Three months post intervention, we evaluated for change in COVID vaccination status, hospitalization, death rates, and patient preferences regarding vaccination. Results: Three months post intervention, a total of 44 patients responded to the survey (39 electronically and 5 via mail). The overall improvement in vaccination rate was 10.4%. Using Fisher’s exact test, we found a statistically significant difference (p = 0.002) in vaccination rates between survey responders compared to non-responders. Vaccination rates increased by 25.0% in survey responders, compared to 7.3% in patients who did not respond. During the study period, 13 patients contracted COVID-19 (1/13 vaccinated), and one patient required hospitalization due to COVID-19 (unvaccinated). No deaths due to COVID-19 were reported. Patients’ most cited reasons for declining vaccination were concerns regarding vaccination safety and lack of understanding of the CDC recommendations. Conclusions: Our study highlights the EMR as an effective means to provide community education about COVID-19 vaccination. Limitations include delayed outreach to patients without electronic patient portal access or with infrequent patient portal use. Nonetheless, our quality study design serves as a model for other implementations of electronic community outreach in oncology patients. Future directions will assess long-term vaccination rates and outcomes in these immunocompromised patients.

MT3 Delphi Panel on the Recommended Use of the Cue COVID-19 at Home Diagnostic Test

The Cue COVID-19 test is an at-home molecular nucleic acid amplification test (NAAT) that detects the RNA of SARS-CoV-2 using a nasal swab sample, with an accuracy rate of 98.9%. This study aims to understand how clinicians who treat immunocompromised (IC) patients view the Cue COVID-19 test, how the Cue COVID-19 test compares to other COVID-19 tests, and the types of IC patients who would benefit from access to Cue COVID-19 tests. Data for the study were collected using a modified Delphi panel methodology. Two sets of electronic surveys were administered in fall 2022 eliciting the opinions of expert panelists on the value of the Cue COVID-19 test, the IC patient population who should be regularly tested for COVID-19, and recommendations on when and how these patients may be tested. Consensus rules were defined a priori; consensus was defined as agreement by ≥ 75% of the panelists. Expert opinions were anonymously collected from eight oncologists/ hematologists/ immunologists with extensive experience treating IC patients in the US. Consensus was achieved that the Cue COVID-19 test would provide value to all IC patients, and that they would benefit from access to this at-home test. Particularly, the panelists agreed that patients would benefit if they were symptomatic, exposed to COVID-19, undergoing chemotherapy, or have HIV with low CD4 count. Panelists recommended that patients should have access to between 1 and 6 Cue COVID-19 tests per month (average of 2.5 tests/month). The study aims to understand the value of the Cue COVID-19 test for IC patients. Clinicians included on this panel agreed that the Cue COVID-19 test would provide value to IC patients, and that IC patients should have access to between 1 and 6 tests per month (average of 2.5 tests/month), for particular use when symptomatic, exposed to COVID-19, or while undergoing chemotherapy.

Economic Evaluation of Evusheld for Preexposure Prevention of COVID-19 in High-Risk Populations: Early Evidence from Thailand.

The introduction of Coronavirus disease 2019 (COVID-19) vaccines urged all Thais to seek prevention of serious illness and death from COVID-19. However, immunocompromised individuals might not be able to achieve an efficient immune response from these vaccines. This study aimed to evaluate the cost-effectiveness and budget impact of introducing Evusheld (tixagevimab plus cilgavimab) for three patient groups-organ transplant, autoimmune disease, and dialysis patients, from the Thai government perspective. A Markov decision model was developed to compare the use of Evusheld plus COVID-19 vaccines versus COVID-19 vaccines alone. The methodology followed the National HTA Guidelines of Thailand. Model input parameters were collected locally from retrospective data and from a literature review. Evusheld helped prevent COVID-19 infection, severe infection, and death in all three patient groups. Using the Thai threshold of 160,000 Thai Baht (THB) per quality-adjusted life year (QALY) gained, the only scenario found to be cost-effective was that of dialysis patients with inadequate immune response, with an incremental cost-effectiveness ratio (ICER) of 54,700 THB per QALY gained. To make a policy of Evusheld provision cost-effective in other groups, the price of Evusheld had to be lower (a reduction of 44-88% of its current price). The results of one-way sensitivity analysis indicated that the cost-effectiveness of Evusheld was sensitive to changes in the rate of infection, cost and efficacy of Evusheld, proportion of inadequate immune responses, and the probability of moving from a 'recovered' to 'susceptible' status. Among three COVID-19-vaccinated immunocompromised patient populations, this study concluded that Evusheld was cost-effective for dialysis patients with inadequate immune response to the COVID-19 vaccine.

Fungal Whole-Genome Sequencing for Species Identification: From Test Development to Clinical Utilization.

Using next-generation sequencing (NGS), we developed and validated a whole-genome sequencing (WGS)-based clinical test for fungal species identification on clinical isolates. The identification is mainly based on the fungal ribosomal internal transcribed spacer (ITS) region as the primary marker, and additional marker and genomic analysis applied for species within the Mucorales family (using the 28S rRNA gene) and Aspergillus genus (using the beta-tubulin gene and k-mer tree-based phylogenetic clustering). The validation study involving 74 unique fungal isolates (22 yeasts, 51 molds, and 1 mushroom-forming fungus) showed high accuracy, with 100% (74/74) concordance on the genus-level identifications and 89.2% (66/74) concordance on the species level. The 8 discrepant results were due to either the limitation of conventional morphology-based methodology or taxonomic changes. After one year of implementation in our clinical laboratory, this fungal NGS test was utilized in 29 cases; the majority of them were transplant and cancer patients. We demonstrated the utility of this test by detailing five case studies, in which accurate fungal species identification led to correct diagnosis, treatment adjustment or was ruled out for hospital acquired infection. This study provides a model for validation and implementation of WGS for fungal identification in a complex health system that serves a large immunocompromised patient population.

Seroconversion following Heplisav-B, hepatitis B vaccine (recombinant), adjuvanted, in patients with end-stage renal disease at an urban safety net hospital.

Heplisav-B is a novel recombinant adjuvanted vaccine for hepatitis B virus (HBV) that has been approved as a 2-dose regimen and shown to have similar seroconversion rates in healthy adults as single-antigen HBV vaccines. More data are needed to determine whether similarly high rates of seroconversion and immunity are observed in immunocompromised patient populations such as in patients with end-stage renal disease (ESRD) on hemodialysis. Patients with ESRD who presented for emergency-only hemodialysis and either were HBV vaccine naive or had a hepatitis B surface antibody (anti-HBs) titer of less than 10 IU/mL received 3 standard 20-μg doses of Heplisav-B at week 0, week 4 (±2 weeks), and week 24 (±2 weeks), with anti-HBs titer measured at week 28 (±2 weeks). Thirty-two patients received at least one dose in the study timeframe, with 24 patients completing the vaccine series and measurement of anti-HBs titer. The mean age of the patients was 46 years, and 58% of patients were male. Of the 24 patients who completed the vaccine series, 20 (83%) seroconverted after the third dose. Three of the 4 patients who did not seroconvert after 3 doses were revaccinated with an additional 20-μg dose, and 2 of the 3 patients had an anti-HBs titer of greater than 10 IU/mL 4 weeks after this dose. Patients with ESRD who received three 20-μg doses of recombinant HBV vaccine had a seroconversion rate of 83%, representing a similar seroconversion rate and fewer doses of vaccine as compared to the standard HBV vaccine regimen for patients with ESRD.

Subnormal Immunity to Inactivated Poliovirus Vaccine (IPV) in Previously Vaccinated Human Immunodeficiency Virus (HIV) - Infected Children

Introduction: Minimal data exists regarding prevalence of immunity to inactivated poliovirus vaccine (IPV) in previously vaccinated HIV-infected children. Methods: Antibody titers to IPV against serotypes (ST) 1, 2 and 3 following 3-doses (primary series) and 4th and 5th doses (booster) were examined in 59 children who were born to HIV-infected mothers. Eight of those children tested negative for HIV by DNA PCR and served as the controls for the 3rd and 4th dose recipients. Anti-polio 1, 2, 3 antibody titers (1/dil) was measured by neutralization assay at Specialty Laboratory in New Jersey. Correlate of protective immunity (PI) was defined as antibody titer &gt;1:8 for all serotypes. ST specific PI was correlated with the T cell counts and clinical disease categories within the HIV-infected children. PI status was compared between the HIV- infected and HIV- uninfected children and between the numbers of vaccine dose recipients within the HIV-infected children. Results: Mean age of children at the time of vaccination was 6.6, 18.6 and 66.5 months in the 3rd, 4th and 5th dose recipients, respectively. The mean age of the HIV-infected and HIV- uninfected children was comparable in the 3-dose group. Among the 3rd and 4th dose recipients, prevalence of PI to all 3 ST was significantly (p= 0.002/ST1, 0.002/ST2 and 0.01/ST3) lower in the HIV-infected, compared to their uninfected counterparts; Within the HIVinfected children, prevalence of PI to ST 1 and 2 was around 7-10 percent for all dose recipients; and 28 percent to ST3 for the 5th dose vaccine recipients. The CD4 count was found to be significantly (p=0.009) lower (362/mm3) in the 5th dose compared to the 3rd dose vaccine recipients (1072 /mm3). Conclusion: A significantly high proportion of HIV- infected children may remain unprotected against all ST of IPV even after their booster doses and thus may remain at risk for infection with all 3 ST of poliovirus when exposed to recipients of the live oral polio vaccine worldwide. Global implementation of IPV over OPV may be considered to prevent resurgence of poliovirus disease in the growing population of immunocompromised patients. Extra vigilance in the maintenance of protective immunity to poliovirus serotypes and surveillance of disease in the immunocompromised host may be deemed necessary for prevention of disease occurrence and timely diagnosis and treatment.

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer.

S3034 Histoplasmosis Infection Presented as Cholestatic Liver Disease

Introduction: Histoplasmosis is the most common mycosis in the United States with peak incidence in the Midwest region. In ∼21% of patients with systemic histoplasmosis hyperbilirubinemia can be detected. However, cholestatic presentation of histoplasmosis infection is very rare. Here we present a case of immunocompromised patient with predominant cholestatic liver disease caused by Histoplasma Capsulatum. Case Description/Methods: This is the case of 56- years- old female who presented with– sided abdominal pain, shortness of breath, chills, hot flushes, nausea, vomiting and diarrhea. She is suffering from rheumatoid arthritis. Her medications are adalimumab, celecoxib, hydroxychloroquine. She denied alcohol intake. Her initial workup including liver function tests (LFTs) was positive for a total bilirubin 3.5 mg/dl, conjugated bilirubin 2.7 mg/dl, alkaline phosphatase – 547 U/L, AST – 152 U/L, ALT-142 U/L, and platelet count – 55 k/ul. During hospitalization her abdominal pain was getting progressively worse, and her LFTs continued to trend up. Eventually liver biopsy was performed. The results showed multiple granulomas with central necrosis, and associated portal and lobular inflammation. The fungal stain highlighted yeasts suggestive of histoplasma. Her urinary histoplasma Ag Quantitative EIA eventually came back positive -8.87 ng/ml. Viewing the normal chest x-ray and ongoing hypoxia, chest CT scan with IV contrast was performed showing 1.1 cm lung nodule in the left lower lobe. A subsequent bronchoscopy revealed budding yeasts. Patient was started on liposomal amphotericin B, and her LFTs trended down. The patient was treated with amphotericin B for 21days subsequently changed to twice-daily oral Itraconazole 200mg. At the outpatient follow up visit, patient admitted a complete resolution of her abdominal pain and improvement of her breathing status. Discussion: Liver histoplasmosis is a rare cause for cholestatic liver disease. Over the past two decades, a limited number of cases with similar clinical scenario were described. Despite of the rarity of this condition, hepatic histoplasmosis should be considered in a selected population of immunocompromised patients living in an endemic area (ex: Ohio). Inclusion of urine antigen testing for histoplasma in early workup can potentially prevent diagnostic delay.