Immunosuppressed Population Research Articles

Immunogenicity and Safety According to Immunosuppressive Drugs and Different COVID-19 Vaccine Platforms in Immune-Mediated Disease: Data from SAFER Cohort

Background/Objectives: The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. Methods: The SAFER study: “Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease”, is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer–BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). Results: 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41–7.24), T2: 73.01 (61.53–86.62), T3: 200.0 (174.36–229.41) and T4: 904.92 (800.49–1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. Conclusions: All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies.

Tumor characteristics in immunosuppressed and renal dysfunction populations

PurposeRenal transplantation and end-stage renal disease are increasingly common. Renal dysfunction and immunosuppression are two risk factors in the development of renal cell carcinoma. Carcinomas in these patients are thought to be more indolent, however data are limited and mixed. Our objective was to describe the histology of resected tumors from the transplant and renal dysfunction population and compare them to a control population. Materials and MethodsThis was a single-center retrospective cohort study of all patients who had a nephrectomy for a renal mass from 2009 to 2019. All transplant status and end-stage renal disease diagnoses were identified by diagnostic or procedural coding and confirmed by chart review. Our primary endpoint was the pathology for each patient's tumor. Tumors were classified into aggressive or nonaggressive categories based on their histology and grade. ResultsWe identified 1,150 radical and partial nephrectomies, of which 1,057 met inclusion criteria. Of these, 68 patients (6.4%) had renal dysfunction or a kidney transplant on immunosuppression at time of nephrectomy. After pathologic review, 270 (25%) tumors were classified as aggressive, and 673 (64%) tumors were pT1a or pT1b. On multivariable logistic regression controlling for age and gender, renal dysfunction was not associated with having an aggressive tumor (OR 1.24, 95%CI 0.72–2.15; P = 0.44). ConclusionsWe did not observe a relationship between renal dysfunction status and aggressive pathology. These data suggest that renal dysfunction and transplant patients are at similar risk for aggressive pathology as the general population and should be managed according to the same clinical guidelines.

5-fluorouracil 5% cream for squamous cell carcinoma in situ: Factors impacting treatment response

Complete clinical response (CCR) rates for squamous cell carcinoma in situ (SCCis) treated with 5-fluorouracil (5-FU) 5% cream range from 27-85%. Factors associated with CCR are not well-established. Retrospective review of biopsy-proven primary SCCis diagnosed between 5/1/2019-4/30/2020 and treated with 5-FU 5% cream. Disease status at follow-up was recorded, with treatment failure defined as persistent or recurrent disease. The study included 149 SCCis cases, including 33.6% (50/149) arising in the context of immunosuppression. Eighteen cases failed treatment (10 persistent disease, 8 recurrent disease). By tumor size, CCR was noted in 128/144 (88.9%) tumors measuring <2 centimeters in diameter and 3/5 tumors ≥2 centimeters (60.0%, p=0.051). By treatment duration, CCR was observed in 4/7 (57.1%) tumors treated for <2 weeks, 72/83 (86.7%), tumors treated for 2 to <4 weeks, and 55/59 (93.2%) tumors treated for ≥4 weeks (p=0.019). On multivariate analysis, treatment failure was significantly associated with shorter treatment durations (OR 0.26; p=0.007) and increasing tumor size (OR 2.40; p=0.037). Shorter treatment duration and larger lesion size were significantly associated with failure of 5-FU in SCCis. Immunosuppression and anatomic location were not significant factors, supporting 5-FU use for SCCis in the immunosuppressed population and highlighting its versatility irrespective of anatomic location.

Evaluating the Efficacy of a Polymerase Chain Reaction Assay for Pneumocystis carinii Detection in Respiratory Samples

Abstract Introduction: Accurately identifying patients with pneumocystis pneumonia (PCP) presents considerable challenges, primarily relying on clinical suspicion. The manifestations of PCP lack specificity, encompassing symptoms such as cough, dyspnoea, fever, hypoxaemia, malaise and weight loss. Therefore, this study assesses the efficacy of a polymerase chain reaction (PCR) assay intended for use in clinical microbiology laboratories for the identification of Pneumocystis carinii from respiratory specimens. Materials and Methods: In this retrospective study, the medical records of patients aged 18 years and above were examined, focusing on those assessed using pneumocystis PCR-based tests. The study spanned from 2019 to 2022 in our tertiary care centre at Max Hospital, Saket. In this study, sputum and bronchoalveolar lavage (BAL) samples were proceeded for both staining and PCR for multi-copy mtLSU gene and single-copy dihydropteroate synthase polymorphisms (DHPS) fas gene of P. jirovecii. Results: In the analysis of 112 BAL specimens, 17 were identified as positive for P. carinii through both Grocott-Gomori’s Methenamine Silver Staining (GMS) staining and PCR. In addition, two BAL specimens were negative through GMS staining but showed positive results with PCR. On reviewing the clinical details of the patients associated with these two specimens, it was discovered that both individuals were under systemic steroid treatment, yet neither exhibited clinical signs of pneumocystis pneumonia (PCP). Consequently, these instances were classified as false positives by PCR. In comparison to GMS, the PCR assay demonstrated a sensitivity of 100% and specificity of 98% for detecting P. carinii in BAL specimens. Conclusions: The study underscores the necessity for individualised approaches, with each laboratory assessing the positive and negative predictive values based on their specific prevalence rates. In the ongoing pursuit of improving PCP diagnosis, PCR emerges as a promising screening tool that when used judiciously in conjunction with confirmatory measures, can enhance diagnostic precision in immunosuppressed populations.

Current Advances and Challenges in the Management of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group.

A Third COVID-19 Vaccine Dose in Kidney Transplant Recipients Induces Antibody Response to Vaccine and Omicron Variants but Shows Limited Ig Subclass Switching.

This study addresses the challenges faced by kidney transplant recipients (KTRs) in mounting effective immune responses against COVID-19. By evaluating the antibody responses to a third dose of monovalent mRNA COVID-19 vaccine and its effectiveness against Omicron subvariants (BA.1 and BA.5), this study reveals significant reductions in both binding and neutralizing antibodies in KTRs compared to healthy controls. The research highlights altered IgG subclass switching and heterogeneous responses within the KTR population. Reduced recognition of variants, coupled with differences in IgG subclasses, decreases both the quality and quantity of protective antibodies after vaccination in KTRs. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.

Adopting prospective antimicrobial stewardship (AMS) practice in high-risk immunosuppressed groups: an urgent call to action in the era of antimicrobial resistance (AMR).

Life-saving immunosuppressive treatments including intensive chemotherapy and bone marrow transplantation expose patients to a considerable risk of death from infection globally. With evolving AMR and transmission, this could spell disaster for patients across the world and society at large. Antimicrobial stewardship (AMS) and prompt appropriate management of potentially fatal, emergent infections are essential. It is now apparent that antibacterial prophylaxis in patients with haematological cancer may not provide survival benefit while simultaneously increasing risks for AMR carriage. With evolving AMR and increasing immunosuppressed populations across the world, we must institute robust AMS practices. Significant resources are used to combat the impact of AMR on immunosuppressed patients. For lower-middle income countries (LMICs) these resources may not be available and as such the impact caused by AMR is greater. By considering the patient journey holistically we consider risk of infection presented to patients temporally and geographically. A short-term and easy to implement approach of multi-disciplinary team (MDT)-style advance care planning for infection is advocated. Antimicrobials, when used appropriately, enable healthcare procedures to occur and exist. Indeed, the very future of clinical medicine will rely on this yet to be realized value of enablement. Proactive effort and change must occur across all sectors with holism; hence our impetus for convening a joint industry and clinical working group. With at-risk immunosuppressed groups being a sentinel for change, awareness and implementation of patient-centric actions for infection are essential and our recommendations serve as an urgent call to action.

Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States.

Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population. We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively). Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.

Prevalence and Risk Factors of Postacute Sequelae of COVID-19 in Adults With Systemic Autoimmune Rheumatic Diseases.

Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

#3080 Response to mRNA SARS-CoV-2 vaccination in kidney transplant recipients with HIV

Abstract Background and Aims No data exists on humoral or cellular responses to mRNA vaccines in kidney transplant recipients (KTR) with HIV. We compared these responses in HIV-positive and negative KTR, as well as in people living with HIV (PLWH) without kidney transplantation. Method In a cross-sectional study of 33 patients receiving two (n=13) or three (n=20) doses of mRNA SARS-CoV-2 vaccination, we evaluated the humoral response to mRNA SARS-CoV-2 vaccination using a Luminex platform for IgG and IgM, and assessed cellular response with specific T cell response with S- and N- protein by ELISpot. We used logistic regression models to assess associated factors. Results The study comprised 11 HIV-negative KTRs (HIV-KTR+), 11 HIV-positive KTRs (HIV+KTR+), and 11 PLWH without kidney transplantation (HIV+KTR−). PLWH had suppressed viral load on ART. Seroconversion rates after two or three vaccine doses were 72.7% among KTRs, with no significant difference between HIV-KTR+ (81.8%) and HIV+KTR+ (63.6%) (P=0.338). In HIV+KTR−, seroconversion was 100%, higher than HIV+KTR+ (P=0.027). Cellular response against protein S occurred in 63.6% cases, irrespective of HIV or transplantation status or number of doses. Protein N reactivity was observed in 27.3% KTRs (HIV-KTR+ and HIV+KTR+), versus 9.1% HIV+KTR− (P=0.378). Higher age negatively influenced cellular response in PLWH (OR 0.77, 95% CI 0.60-0.99). Conclusion Although cellular immune response was similar across all groups, we found a reduced humoral response in HIV+KTR+. In PLWH, higher age reduced cellular response. These findings contribute to our understanding of vaccine response in immunosuppressed populations and provide valuable insights for optimizing vaccination strategies.

Prognostic factors in Kaposi sarcoma, single centre experience.

Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV-8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. During the follow-up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer.

Incidence, Risk Factors, and Outcomes of De Novo Malignancy following Kidney Transplantation.

Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.

A systemic infection involved in lung, brain and spine caused by Scedosporium apiospermum species complex after near-drowning: a case report and literature review

Scedosporium apiospermum species complex are widely distributed fungi that can be found in a variety of polluted environments, including soil, sewage, and decaying vegetation. Those opportunistic pathogens with strong potential of invasion commonly affect immunosuppressed populations However, few cases of scedosporiosis are reported in immunocompetent individuals, who might be misdiagnosed, leading to a high mortality rate. Here, we reported an immunocompetent case of systemtic infection involved in lung, brain and spine, caused by S. apiospermum species complex (S. apiospermum and S. boydii). The patient was an elderly male with persistent fever and systemtic infection after near-drowning. In the two tertiary hospitals he visited, definite diagnosis was extremely difficult. After being admitted to our hospital, he was misdiagnosed as tuberculosis infection, before diagnosis of S. apiospermum species complex infection by the metagenomic next-generation sequencing. His symptoms were alleviated after voriconazole treatment. In the present case, the details associated with its course were reported and published studies on Scedosporium spp. infection were also reviewed, for a better understanding of this disease and reducing the misdiagnosis rate.

Non-O1/non-O139 Vibrio cholerae bacteraemia and cholangitis: An unusual case in an oncological patient in Lecco Hospital, Italy

Vibrio species are curved, motile, aerobic and facultative anaerobic, Gram-negative bacilli that are widely distributed in aquatic environments, especially marine and estuarine waters. Vibrios of primary concern in human pathology are essentially represented by the species Vibrio cholerae. Classification of Vibrio cholerae is based on the O-antigen polysaccharide type, with over 200 serogroups described. Historically, only toxigenic serogroups O1 and O139 have been associated with widespread cholera epidemics. Other serogroups can cause small outbreaks that spread via contaminated raw seafood (primarily shellfish and molluscs) and seawater exposure, and they are collectively termed Non-O1/Non-O139 Vibrio Cholerae (NOVC). NOVC, occasionally detected also in the Mediterranean Sea, most often causes sporadic gastrointestinal manifestations requiring supportive therapy. However, rarely the V. cholerae non-O1/ non-O139 serotype can result in extraintestinal manifestations such as severe wound infections, soft tissue infections and sepsis in immunocompromised patients that represent a therapeutic challenge. In particular, NOVC bacteraemia is a rare event but has the highest mortality rates among NOVC infections (almost 33%) and usually occurs in certain immunosuppressed populations, such as patients with haematologic and solid malignancies, and those with underlying liver disease.

The Burden of Invasive Fungal Disease Following Chimeric Antigen Receptor T-Cell Therapy and Strategies for Prevention.

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy approved for the treatment of hematologic malignancies. This therapy leads to a variety of immunologic deficits that could place patients at risk for invasive fungal disease (IFD). Studies assessing IFD in this setting are limited by inconsistent definitions and heterogeneity in prophylaxis use, although the incidence of IFD after CAR T-cell therapy, particularly for lymphoma and myeloma, appears to be low. This review evaluates the incidence of IFD after CAR T-cell therapy, and discusses optimal approaches to prevention, highlighting areas that require further study as well as future applications of cellular therapy that may impact IFD risk. As the use of CAR T-cell therapy continues to expand for hematologic malignancies, solid tumors, and most recently to include non-oncologic diseases, understanding the risk for IFD in this uniquely immunosuppressed population is imperative to prevent morbidity and mortality.

Underrecognized cause diarrhea in solid organ transplant: a report of astroviridae enteritis in liver transplant.

We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery diarrhea. He was found to have Astrovirus via PCR testing in a comprehensive stool panel. The patient's home mycophenolic acid was held upon admission, while cyclosporine was continued through his hospital stay. Generally, Astroviridae infection is a rarely identified cause of enteritis and even less so in the transplant population. Although reports have been published regarding devastating cases of encephalitis in immunocompromised patients, our patient did not exhibit these symptoms and draws into question the danger of this virus in other immunosuppressed populations. This case helps to better elucidate which patient populations should be approached with caution in the setting of Astroviridae infection.

Dissecting the genome sequence of a clinical isolated Cunninghamella bertholletiae Z2 strain with rich cytochrome P450 enzymes (Article)

Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14 year, 9 months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30.9 Mb with 9213 genes. Mucoral specific virulence factor genes found are ARF, CalN, and CoTH, while no gliotoxin biosynthesis gene cluster was found, which is a known virulence factor in Aspergillus fumigatus adapted to the environment. The Z2 strain was found to have 69 cytochrome P450 enzymes, which are potential drug resistant targets. Sensitivity testing of Z2 showed it was only inhibited by amphotericin B and posaconazole. Detailed genomic information of the C. bertholletiae Z2 strain may provide useful data for treatment.

Efficacy of SARS-CoV-2 Vaccine Doses in Allogeneic Hemopoietic Stem Cell Recipients: A Systematic Review and Meta-Analysis.

Recipients of allogeneic hematopoietic cell transplantation (alloHCT) are at increased risk of morbidity and mortality due to COVID-19. Immune responses to SARS-CoV-2 vaccines are blunted in these profoundly immunocompromised patients. As a result, novel strategies for protection, such as additional vaccine doses (boosters), are being explored. However, data regarding the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients are limited and conflicting. In this systematic review and meta-analysis, we investigated the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients. The review was conducted following PRISMA guidelines, and 7 studies with 385 alloHCT recipients who received 3 vaccine doses were included. The primary outcomes assessed were the rate of seroconversion following the third dose of vaccine and the rate of seroconversion in patients who did not respond to the initial 2-dose vaccination series. The pooled humoral response rate after 3 doses of SARS-CoV-2 vaccine in alloHCT recipients was 74%. In a subgroup analysis of patients who did not respond to the initial 2-dose series, the seroconversion rate following the third vaccine dose was 49%. Notably, male patients and those with a shorter interval between alloHCT and the first vaccine dose were more likely to not respond to the third dose. In conclusion, the pooled humoral response rate of 74% following three doses of SARS-CoV-2 vaccine in alloHCT recipients highlights the potential for protection in this immunosuppressed population. Additionally, encouraging responses in nearly half of the patients who did not seroconvert with the initial 2-dose series suggest the continued utilization of additional vaccine doses until results from large prospective studies become available. These findings are critical for informing vaccination strategies in alloHCT recipients to mitigate the high mortality risk associated with COVID-19.

Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls.

Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population. Clinical Trials Registration. NCT04969263.

2475. Admissions Screening for Influenza and RSV Among a Highly Immunosuppressed Patient Population

Abstract Background During the Fall/Winter 2022-23, the U.S. experienced an early surge of Influenza and RSV cases, while SARS-CoV-2 cases persisted. With concerns of a potential “tripledemic” on the horizon, the NIH Clinical Center, a clinical research hospital with a heavily immunosuppressed patient population, implemented Influenza and RSV testing, in addition to SARS-CoV-2, for all patients on admission to facilitate early detection and prompt isolation of infected patients. Methods Nasopharyngeal (NP) swabs (n=1213) were collected on admission from 11/2022 to 4/2023 and tested for Influenza and RSV by PCR. 1213 NP swabs from 985 unique patients were tested (some patients had multiple admissions); 1100 were tested on the Panther Fusion® SARS-CoV-2 Assay (Hologic, Inc.) and 113 using the SARS-CoV-2 RT-PCR Xpert® Xpress test. Medical chart reviews and discussions with patient care providers elucidated whether cases identified on admission were asymptomatic. Results Of 1213 NP swabs collected from patients admitted to our hospital, 5 (0.41%) were identified with Influenza A infection, 4 (0.33%) RSV infection and no patients were identified with Influenza B. Two (0.16%) had a known history of RSV infection, 3 (0.25%) screened negative for symptoms but subsequently disclosed symptoms, 1 (0.08%) was asymptomatic on admission but disclosed a recent history of an upper respiratory infection, and 3 were asymptomatic. All infections were detected between late November 2022 to mid-January 2023, when community transmission was high, yielding a 2-month positivity rate of 2.3% during this time of peak community spread. Conclusion Admission surveillance for Influenza and RSV during a respiratory virus surge in our community allowed us to isolate nine patients on admission who would likely not have been appropriately isolated, as symptom screening alone is not reliable. Surveillance is important to be able to identify infected patients promptly when respiratory infections are rampant in the community, and especially for institutions serving immunosuppressed patients. Disclosures All Authors: No reported disclosures