Groups Of Immunocompromised Patients Research Articles

Implementation of AZD7442 (Tixagevimab/Cilgavimab) COVID-19 Pre-exposure Prophylaxis (PrEP) in the Largest Health Maintenance Organization in Israel: Real-world Uptake and Sociodemographic and Clinical Characteristics Across Immunocompromised Patient Groups.

AZD7442 is a combination of two neutralizing antibodies (tixagevimab/cilgavimab) with demonstrated efficacy in reducing the risk of symptomatic coronavirus disease 2019 (COVID-19) among individuals at high risk of severe COVID-19 ≤ 6months after administration. On February 15, 2022, the Israeli Ministry of Health (IMoH) authorized the administration of 300mg AZD7442 as pre-exposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2infection among immunocompromised individuals aged ≥ 12years. This study describes the real-world uptake of AZD7442 in Israel. This descriptive, observational study analyzed data from Israel's largest health maintenance organization, Clalit Health Services (CHS). Individuals were assessed for AZD7442 eligibility between February 13 and December 11, 2022, and were included if they were aged ≥ 12years, had ≥ 1year of continuous CHS membership, had≥ 1 moderate or severe immunocompromising condition, and were eligible for AZD7442 per IMoH recommendations during this time frame. Overall, 19,161 AZD7442-eligible individuals with immunocompromising conditions were identified during the study period; 2829 (14.8%) received AZD7442. A higher proportion of individuals receiving AZD7442 were older (aged ≥ 65years), male, not current smokers and residents in large cities; required more physician visits (> 50 visits); and had ≥ 1 COVID-19 hospitalization over 12months, while uptake was lowest among ultra-orthodox Jewish individuals. AZD7442 uptake was also higher among individuals with multiple comorbidities (Charlson Comorbidity Index ≥ 5), including hypertension, diabetes and chronic kidney disease. In specific immunocompromised types, AZD7442 uptake was highest among individuals with lung transplantation (41%), primary immunodeficiency (32%), bone marrow transplantation (29%) and multiple myeloma (25%) or those receiving anti-CD20 therapy (26%) and was lowest in individuals with lymphoma (8%). These results show AZD7442 uptake among the eligible population of Israel in 2022 was relatively low, at 14.8%. Uptake was generally higher among immunocompromised individuals who may be perceived to be frail or at highest risk of COVID-19 infection and complications, although at 25-41%, further improvements in uptake would be more impactful. These results also indicate there is opportunity to expand AZD7442 uptake across immunocompromised groups and ensure more equitable uptake among some other sociodemographic groups. Overall, this study will help inform and reassess future implementation strategies for vulnerable populations.

Increased Risk of Invasive Aspergillosis in Immunocompromised Patients With Persistent SARS-CoV-2 Viral Shedding >8 Weeks, Retrospective Case-control Study.

Immunocompromised patients now represent the population most at risk for severe coronavirus disease 2019. Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was reported in these patients ranging from several weeks up to 9 months. We conducted a bicentric retrospective case-control study to identify risk and prognostic factors associated with persistent viral shedding in immunocompromised patients. Symptomatic immunocompromised adults with persistent SARS-CoV-2 viral shedding >8 weeks were retrospectively included between 1 March 2020 and 24 April 2022 at 2 university hospitals in Paris, France, and matched with a control group consisting of symptomatic immunocompromised patients without persistent viral shedding. Twenty-nine immunocompromised patients with persistent viral shedding were compared with 40 controls. In multivariate analysis, fever and lymphocytopenia (<0.5 G/L) were associated with an increased risk of persistent viral shedding (odds ratio [OR]: 3.3; 95% confidence interval [CI], 1.01-11.09) P = .048 and OR: 4.3; 95% CI, 1.2-14.7; P = .019, respectively). Unvaccinated patients had a 6-fold increased risk of persistent viral shedding (OR, 6.6; 95% CI, 1.7-25.1; P = .006). Patients with persistent viral shedding were at risk of hospitalization (OR: 4.8; 95 CI, 1.5-15.6; P = .008), invasive aspergillosis (OR: 10.17; 95 CI, 1.15-89.8; P = .037) and death (log-rank test <0.01). Vaccine coverage was protective against SARS-CoV-2 persistent viral shedding in immunocompromised patients. This new group of immunocompromised patients with SARS-CoV-2 persistent viral shedding is at risk of developing invasive aspergillosis and death and should therefore be systematically screened for this fungal infection for as long as the viral shedding persists.

COVID-19 Related Mortality Does Not Correlate with Vaccine Availability in Leukemia Patients: 2020-2023 Analysis in the United States

Introduction: Leukemia patients have abnormal immune function due to both the innate characteristics of their disease and the treatments, which are almost invariably immunosuppressive in nature. Treatment modalities may lead to both temporary and long term immunosuppression. For these reasons, the coronavirus disease 2019 (COVID-19) pandemic has posed challenges to the management of patients with leukemia.With the approval of several types of COVID-19 vaccines, the first of which became available in December 2020, there has been a significant decrease in morality from COVID-19 among vaccinated adults compared to unvaccinated adults. It is unclear if the same trend applies to adults with leukemia who may have an impaired immune response to vaccination. To further elucidate the efficacy of COVID-19 vaccination in this inherently immunocompromised group of patients, we performed a nationwide analysis of COVID-19 mortality trends in adults over 25 years old with leukemia. Methods: Using the CDC Wonder Database, we reviewed death certificates for COVID-19 related mortality trends from March 2020 to June 2023 for all subtypes of leukemia in the United States in adults above 25 years old. We included respective ICD codes: C91 lymphoid leukemia, C92 myeloid leukemia, C93 monocytic leukemia, C94 other leukemias of specified cell types, and C95 leukemia of unspecified cell types. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people. Data was stratified by reported sex, race/ethnicity, and census region. Results: Deaths from COVID-19 in people with leukemia were reported as 1800 in 2020, 2813 in 2021, 2445 in 2022, and 481 as of June 2023 (Figure 1). There were fluctuations of COVID-19 AAMR per 100,000 people with all subtypes of leukemia from 2020 to 2023 (Table 1). The provisional and incomplete data in 2023 showed a sudden decrease of AAMR within all groups. In 2020 the overall AAMR in all groups was 0.7 which increased to 1.1 in 2021, decreased to 0.9 in 2022, and 0.2 as of June 2023. There is a difference in mortality rates between sex with male AAMR being greater than female in all 3 years. For example in 2021 the AAMR for males was 1.4 while for females it was 0.6. Analysis of racial and ethnic groups showed Asians with the lowest AAMR (0.3 AAMR, 2020) compared to Whites (1.5 AAMR, 2020), Blacks (0.9 AAMR, 2020), and Hispanics (0.6 AAMR, 2020). The trends between the census regions were also comparable. Conclusion: The data demonstrates variations in AAMRs from each year to the next. These variations can be affected by infection rates, public health measures, healthcare access, and socioeconomic factors. The 2023 data is still provisional and incomplete, however, they do offer a glimpse of the 2023 trends. The multiple subtypes of leukemia have different degrees of immunosuppression, thus not all leukemia patients have the same risk profile. Despite the type of Leukemia, it is widely accepted that these patients are in an immunocompromised state and at a higher risk to develop complications from COVID-19. It is recommended for all patients with leukemia to receive non-live, attenuated viral vaccines. Although considered safe and recommended, there is very limited data regarding efficacy of the COVID-19 vaccine in immunocompromised patients. One study showed patients with CLL about 36% of patients were seronegative after vaccination (Chatzikonstantinou et al., 2021) and seronegativity rates may be even higher in patients with acute leukemias. Certainly the absence of steady downward trend in mortality following the availability of vaccination suggests either that leukemia patients are not complying with vaccination recommendations or that vaccination is often ineffective in the setting of their inherent immunocompromise. Certainly a limitation of this analysis is the lack of data regarding COVID-related mortality in vaccinated versus unvaccinated individuals. Given the lack of improvement in AAMR among leukemic patients following the availability of a COVID 19 vaccination, it seems appropriate that physicians still recommend using additional preventative measures from COVID-19 including social distancing and mask wearing. It is important to continue studying the relationship between serology positivity, immunity, and overall outcomes.

501. Risk Factors for Persistent Active COVID-19 Among Patients Receiving B-Cell Depleting Therapy versus Non-B-Cell Immunosuppression

Abstract Background Cases of COVID-19 characterized by prolonged replication of SARS-CoV-2 (persistent active COVID [PAC]) have been reported among immunocompromised patients, particularly those receiving B-cell depleting therapy (BCDT); however, the risk has not been quantified. We aimed to identify risk factors associated with PAC, including quantifying the risk associated with receipt of BCDT vs. other types of immunosuppression. Methods We retrospectively identified four groups of immunocompromised patients who tested positive for SARS-CoV-2 between 4/01/2020 and 4/30/2021. These groups included one group of patients who received an anti-CD20 BCDT within 1 year before a positive SARS-CoV-2 PCR and three groups who received non-BCDT which included hematopoietic cell transplant (HCT) recipients, solid organ transplant (SOT) recipients, and patients receiving chemotherapy for hematologic malignancies (HM). Chart review was performed to characterize the clinical course and development of PAC, which was defined as any of the following: (1) initial clinical improvement followed by progression of illness extending beyond 14 days, characterized by persistent fevers or progressive respiratory failure; or (2) persistent symptoms with demonstration of absent seroconversion ≥ 14 days into illness. This distinction may be supported by low crossing thresholds that occurred ≥ 14 days into illness. Logistic models were performed to identify factors associated with development of PAC and other COVID outcomes. Results We identified 67 COVID-positive patients who had received BCDT as well as 30 HM, 118 SOT, and 29 HCT patients. PAC occurred in 15/67 (22%) of patients receiving BCDT vs. 3/177 (1.7%) patients (all SOT recipients) in the non-BCTD group (SOT, HCT, HM) (Odds Ratio, 16.7; 95% confidence interval [CI] 4.7 to 60.0; p=0.00005). 30-day hospitalization and 90-day mortality were similar in BCDT and non-BCDT groups (Table 1, Figure 1) (p &amp;gt; 0.05). Table 1. Risk factors for specific outcomes of COVID-19 Figure 1. Proportion of patients from each cohort of immunocompromised patients who developed persistent active COVID (1A), required hospitalization within 30 days (1B), required mechanical ventilation (1C), required ICU admission (1D), or died within 90 days after diagnosis of COVID-19 (1E) Conclusion Receipt of BCDTs was significantly associated with the development of PAC in comparison to other forms of severe immunosuppression. However, rates of severe outcomes associated with COVID-19 were similar across all groups. More research is necessary to determine effective prevention or treatment strategies for PAC. Disclosures All Authors: No reported disclosures

Abstract 18142: A Silent Heart Break: An Uncommon Case of Silent Mitral Valve Perforation Secondary to Infective Endocarditis

Introduction: Infective Endocarditis (IE) is an endocardial surface infection of the heart which may lead to valve damage and if severe, this may even lead to valve perforation which can cause significant regurgitation and cardiac function compromise. We present an uncommon case of IE complicated by mitral valve perforation. Case presentation: A 46-year old male with AIDS and polysubstance use was brought to the ED from a shelter after exhibiting erratic behavior with confusion. On exam, he was febrile and tachycardic. Lab data pertinent for lacticaemia and leukocytosis. Blood cultures grew Streptococcus Pneumoniae. MRI Brain was unremarkable. Echocardiography was unremarkable. Antibiotic was initiated leading to marked improvement in patient’s mental status. Despite clinical improvement, days into hospital course, a new holosystolic murmur was audible with left axillary radiation necessitating a repeat echocardiogram which revealed moderate-to-severe mitral eccentric jet regurgitation concerning for anterior leaflet perforation. He remained euvolemic without symptoms of heart failure and was subsequently transferred to a tertiary facility where a mitral valve surgery replacement was scheduled. Discussion: Most patients with infective endocarditis have no preceding valvular abnormality. This case is unusual as there was valvular perforation with no evidence of valvular involvement on prior imaging which could possibly be as a result of invasive streptococcus pneumonia IE potentially coexisting with bacterial meningitis which carries a high mortality rate. Invasive streptococcus pneumonia is an unusual cause of IE since wide availability of antibiotics and vaccines. This case reminds us of the need of thorough physical exam and sequential imaging in such immunocompromised patient groups. Conclusions: A high suspicion for mitral valve perforation should be maintained in patients with invasive streptococcus pneumoniae and new cardiac murmur.

Humoral and Cellular Immunity Are Significantly Affected in Renal Transplant Recipients, following Vaccination with BNT162b2.

Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Humoral immunity was assessed using anti-receptor binding domain (RBD) and neutralizing antibodies (NAb) serum levels measured by ELISA, and cellular immunity was assessed using T-, B-, NK, natural killer-like T (NKT)-cell subpopulations, and monocytes measured by flow cytometry, and also specific T-cell immunity, at predefined time points after BNT162b2 vaccination, in 57 adult RTRs. Administration of three booster doses was necessary to achieve anti-RBD and NAb protective levels in almost all patients (92.98%). Ab production, at several time points, was positively correlated with the corresponding renal function and inversely correlated with hemodialysis vintage (HDV) and treatment with mycophenolic acid (MPA). A gradual rise in several cell subpopulations, including total lymphocytes (p = 0.026), memory B cells (p = 0.028), activated CD4 (p = 0.005), and CD8 cells (p = 0.001), was observed even after the third vaccination dose, while a significant reduction in CD3+PD1+ (p = 0.002), NKT (p = 0.011), and activated NKT cells (p = 0.034) was noted during the same time interval. Moreover, SARS-CoV-2-specific T-cells were present in 41% of the patients who were unable to develop Nabs, and their positivity rates four months after the second dose were in inverse correlation with monocytes (p = 0.045) and NKT cells (p = 0.01). SARS-CoV-2-specific T-cell responses preceded the humoral ones, while two booster doses were needed for this group of immunocompromised patients to mount a protective immune response.

Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a one-year follow-up of the prospective clinical trial COVAXID.

Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection. In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARS-CoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication. The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies. The present studies were supported by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet.

SARS-CoV-2 m-RNA Vaccine Response in Immunocompromised Patients: A Monocentric Study Comparing Cancer, People Living with HIV, Hematopoietic Stem Cell Transplant Patients and Lung Transplant Recipients.

Immunocompromised patients (ICPs) have a higher risk of developing severe forms of COVID-19 and experience a higher burden of complications and mortality than the general population. However, recent studies have suggested that the antibody response to SARS-CoV-2 mRNA vaccines could be highly variable among different ICPs. Using a collaborative, monocentric, prospective cohort study, we assessed anti-SARS-CoV-2 spike protein antibody titers following two and three doses of mRNA vaccines in four groups of ICPs (cancer [n = 232]: hematopoietic stem cell transplant [HSCT; n = 126] patients; people living with HIV [PLWH; n = 131]; and lung transplant [LT; n = 39] recipients) treated at Geneva University Hospitals; and healthy individuals (n = 49). After primo-vaccination, the highest anti-S antibody geometric mean titer (IU/mL) was observed in healthy individuals (2417 IU/mL [95% CI: 2327-2500]), the PLWH group (2024 IU/mL [95% CI:1854-2209]) and patients with cancer (840 IU/mL [95% CI: 625-1129]), whereas patients in the HSCT and LT groups had weaker antibody responses (198 IU/mL [95% CI: 108-361] and 7.3 IU/mL [95% CI: 2.5-22]). The booster dose conferred a high antibody response after 1 month in both PLWH (2500 IU/mL) and cancer patients (2386 IU/mL [95% CI: 2182-2500]), a moderate response in HSCT patients (521 IU/mL [95% CI: 306-885]) and a poor response in LT recipients (84 IU/mL [95% CI: 18-389]). Contemporary treatment with immunosuppressive drugs used in transplantation or chemotherapy was associated with a poor response to vaccination. Our findings confirmed the heterogeneity of the humoral response after mRNA vaccines among different ICPs and the need for personalized recommendations for each of these different groups.

Investigation of Blastocystis hominis Frequency in Patients with Diabetes by Microscopy and Conventional PCR Methods.

We aimed to determine the frequency and subtype of B. hominis in diabetic patients. One hundred and fifty diabetic patients and 100 healthy people without any chronic disease were included in the study. Stool samples were analyzed by native-Lugol, condensation, trichrome staining and PCR methods. İn 150 patients with diabetes; B. hominis was detected in 38 (25.3%) by PCR, in 34 (22.7%) by native-Lugol and trichrome staining. In the control group, 14 (14%) out of 100 subjects were positive by PCR, and 10 (10%) were positive by native-Lugol and trichrome staining. In the statistical evaluation, a significant difference was found between gender (P=0.023), age (P=0.045; ≤35 and >35 comparison), duration of diabetes (P=0.04), the HbA1c value (P=0.023; <8 and ≥8 comparison), and B. hominis positivity. ST1 was determined in 76.9% of patients with diabetes, and ST2 was determined in 23.07%. Considering the 3 methods, B. hominis positivity was detected in 40 patients (26.7%) in diabetic group and in 14 participants (14%) in the control group (P=0.011). B. hominis is a factor to be considered in patients with diabetes. Herein, the most common subtype detected in the patients with diabetes mellitus was ST1, but this result was not considered sufficient to reveal the importance of the subtype factor in the pathogenicity of B. hominis in patients with diabetes. In this context, there is a need for more comprehensive studies in both diabetic and other immunocompromised patient groups.

Preliminary Evidence of Good Safety Profile and Outcomes of Early Treatment with Tixagevimab/Cilgavimab Compared to Previously Employed Monoclonal Antibodies for COVID-19 in Immunocompromised Patients.

Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalisation and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson's chi-square or Fisher's exact test for categorical variables, whereas the Wilcoxon rank-sum test was employed for continuous ones. Kaplan-Meier curves were produced to compare the time to nasopharyngeal swab negativity. Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups regarding clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p = 0.088) emerged. Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs.

Detection of Pneumocystis jirovecii by PCR in patients with lung cancer: A preliminary study.

Infection complications in lung cancer (LC), one of the most common cancers in the world, are still among the most important causes of death. Of them, P. jirovecii, which is as an opportunistic infection, causes a life-threatening type of pneumonia in cancer patients. This preliminary study aimed to determine the incidence and clinical status of P. jirovecii by PCR in lung cancer patients compared to the conventional method. Sixty-nine lung cancer patients and fSorty healthy individuals were included in the study. After sociodemographical and clinical features were recorded, sputum samples were collected from attenders. Firstly, microscopic examination was made with Gomori's methenamine silver stain and then PCR was performed. P. jirovecii was detected in three of 69 lung cancer patients by PCR (4.3%), but not by microscopy. However, healthy individuals were negative for P. jirovecii by both methods. Based on clinical and radiological findings, P. jirovecii was evaluated as probable infection in one patient and colonization in the other two patients. Although PCR is more sensitive than conventional staining methods, it cannot distinguish probable and proven infections from pulmonary colonization. It is important to evaluate the decision of infection together with laboratory, clinical and radiological findings. Moreover, PCR may enable to know the colonization and to take precautions such as prophylaxis, due to the risk of colonization turning into an infection in immunocompromised patient groups. Further studies involving larger populations and evaluating the colonization-infection relationship in patients with solid tumors are needed.

The Role of Anti-Sperm Antibodies in Primary, Secondary, Immunological and Idiopathic Infertility in Men

The current study aimed to conduct a statistical study to find out the numbers of men with primary and secondary infertility, immunological infertility and Idiopathic infertility in the city of Tikrit with an estimate of the levels of some sex hormones and physiological and immunological variables. The study included 400 married men who attended the Urology Department at Salah Al-Din Hospital and private clinics in the city of Tikrit and its environs for the period from April 2021 to February 2022, and their ages ranged from (20-50) years, and they were divided into two main groups as follows: It included (80) men, and it was divided into four sub-groups, namely: - The group of patients with primary infertility and included 20 individuals. The group of patients with secondary infertility included 20 individuals. And the group of immunocompromised patients included 20 individuals. And the group of patients with unexplained infertility included 20 individuals. The group of natural (fertile) individuals: It is the fifth group and represents the control group, which included (20) individuals. The results showed that the percentage of primary infertility was the highest among infertile patients, reaching 41%, while the percentage was lowest for immunological infertility, reaching 7%. While the percentage of secondary and unexplained infertility was 21% and 31%, respectively. On the other hand, the results showed that there were significant differences (P&lt;0.05) in sperm parameters between the study groups, as sperm concentrations and the percentage of mobile sperm showed a significant decrease (P&lt;0.05), especially in the secondary infertility group compared to the control group. As for the percentage of slow-moving sperms, there were no significant changes (P&lt;0.05) in all infertile groups compared with the control group. As for the percentage of non-motile sperms, it showed a significant increase (P&lt;0.05), especially in the unexplained infertility group compared with the control group. With regard to sperm shape, the percentage of deformed sperm showed a significant increase (P&lt;0.05), especially in the primary infertility group compared with the control group. The results of the current study also showed that there were significant differences (P &lt; 0.05) in the concentrations of hormones between the study groups, as the concentrations of testosterone showed a significant decrease (P &lt; 0.05), especially in the primary infertility group compared with the control group, while the least significant decrease was recorded (P&lt;0.05) in testosterone concentration in the unexplained infertility group. Regarding the prolactin hormone, a significant increase (P&lt;0.05) was recorded in the infertility groups compared with the control group, as it was significantly higher in the secondary infertility group. LH also showed significant differences (P&lt;0.05) between the study groups, and the highest significant increase was in the primary infertility group compared to the control group, while the unexplained infertility group did not show any significant differences compared to the control group. As for the FSH hormone, it showed significant differences (P&lt;0.05) between the study groups, as it recorded the highest significant increase in the primary infertility group compared to the control group, while the unexplained infertility group did not show any significant differences compared to the control group. The results of the current study also showed that there were significant differences (P&lt;0.05) in the concentrations of immunoglobulins between the study groups, as the concentrations of IgA showed a significant decrease (P&lt;0.05), especially in the secondary infertility group compared with the control group, while the least significant increase was recorded (P&lt;0.05). 0.05) in the concentration of IgA in the immunocompromised group. Regarding IgG, a significant increase (P&lt;0.05) was recorded in the infertile groups compared with the control group, if the highest significant increase was in the immunocompromised group. While the primary and secondary infertility group did not show any significant differences compared to the control group. IgM showed significant differences (P &lt; 0.05) between the study groups, and the highest significant increase was in the immunocompromised infertility group compared with the control group, while the primary and secondary infertility groups did not show any significant differences compared with the control group. Also, ASA concentrations showed a significant increase (P&lt;0.05), especially in the unexplained infertility group, while no significant change (P&lt;0.05) was recorded in the ASA concentration in the primary infertility group. With regard to white blood cells, the percentage of white blood cells showed a significant increase (P&lt;0.05), especially in the group of immunocompromised infertility, while the percentage of white blood cells was lowest in the group of primary infertility.

Safety and Immunogenicity of Covid-19 Vaccines in Patients with Cancer: A Network Meta-Analysis of 11357 Patients

Background: The COVID-19 pandemic has had a devastating impact worldwide, especially among patients with cancer as they are more likely to experience severe infection and worse outcomes than the general population. Cancer patients have been excluded from the confirmatory clinical trials which create a gap in the clinical data addressing the effectiveness and safety of the vaccines in this group of immunocompromised patients. Therefore, this study aims to evaluate the findings of all relevant individual studies about the serological response to COVID-19 vaccines in cancer patients compared with healthy participants.&#x0D; Method: We searched for published relevant studies in the following electronic databases: PubMed, Scopus, Cochrane Library, and Web of Science from inception until 1st August 2022. Data were extracted from eligible studies and pooled as a risk ratio or mean difference (MD) in the network meta-analysis model with the corresponding 95% confidence interval. We used the random effect model in case of significant heterogeneity, otherwise, a fixed-effect model was used. We analyzed the data using R version 4 for windows.&#x0D; Results: We included 42 studies (3 randomized controlled trials and 39 observational) with a total of 11357 patients in this network meta-analysis. The pooled effect estimates showed that healthy participants were better than cancer patients with solid and hematological tumors in seroconversion [(RR = 0.81; 95% CI 0.75, 0.87; P &lt; 0.00001)), (RR = 0.61; 95% CI 0.54, 0.69; P &lt; 0.00001); respectively]. However, the pooled effect estimates showed that there was no difference between healthy participants and Cancer patients with solid tumors in terms of Covid-19 antibody titer, T-cell response, and adverse events (MD = -160.82; 95% CI -3089.28, 2768.18; P = 0.91), (RR = 1.10; 95% CI 0.69,1.75; P = 0.69), (RR = 1.06; 95% CI 0.88,1.27; P= 0.54), respectively. Additionally, there was no significant difference between the different types of vaccines in terms of COVID-19 antibody titer.&#x0D; Conclusion: In conclusion, the current evidence demonstrated that the seroconversion rate in healthy participants was higher than in patients with solid and hematological cancers. Nevertheless, our network meta-analysis revealed no significant difference between the two groups in terms of Covid-19 antibody titer, T-cell response, and adverse events. Accordingly, the present evidence is not sufficient to confirm the safety and efficacy of covid-19 vaccine among cancer patients. Therefore, further studies are recommended.

Immunogenicity and Safety of SpikoGen, an Adjuvanted Recombinant SARS-CoV-2 Spike Protein, as a Heterologous Third Booster Dose in Kidney Transplant Patients: A Single-arm Clinical Trial

PurposeStudies have found that immunocompromised patients have suboptimal responses to COVID-19 vaccines, leading to approval of a need for booster doses in this population. SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2™ adjuvant to protect against COVID-19. Previous clinical trials found this vaccine to be tolerable, immunogenic, and efficacious in reducing the risk of COVID-19, including severe disease. However, the effects of this vaccine have not been assessed in immunocompromised patients. This study sought to assess the immunogenicity and safety of the SpikoGen vaccine as a third booster dose in patients undergoing kidney transplant who were receiving immunosuppressive therapy and had received their primary vaccination based on an inactivated whole virus platform (Sinopharm). MethodsThis single-arm trial was performed with 43 patients undergoing kidney transplant. The participants received a single booster dose of the SpikoGen vaccine 1 to 3 months after primary vaccination with 2 doses of the Sinopharm vaccine. Immunogenicity assessments were performed at baseline and 30 days after the booster dose. The primary outcomes were seroconversion rates of anti-S1 and surrogate virus neutralizing antibodies. Safety outcomes included the incidence of solicited and unsolicited adverse events in the 7 days and 1 month after the booster dose, respectively. FindingsThe SpikoGen vaccine induced positive humoral and cellular responses 30 days after the booster dose in those patients who were seropositive or seronegative after 2 primary doses of the Sinopharm vaccine. Thirty days after the SpikoGen vaccine booster, seroconversion rates were 35.29% (95% CI, 19.75%–53.51%) to anti-S1 and 29.41% (95% CI, 13.27%–46.57%) to surrogate neutralizing antibodies. The most common local and systemic reported solicited adverse events were injection site pain and fatigue, which were largely mild and transient. No serious adverse events were reported. ImplicationsA single booster dose of SpikoGen vaccine given 1 to 3 months after primary vaccination with 2 doses of Sinopharm vaccine induced positive humoral and cellular immune responses in immunosuppressed patients undergoing renal transplant, thereby achieving spike antibody levels predictive of protection. This study was performed as a single-center study, and it will be important for future large multicenter studies to extend these results to other immunocompromised patient groups.

Molecular investigation of Blastocystis sp. and its subtypes in cancer patients under chemotherapy in Aegean region, Turkey

Blastocystis sp. is a common enteric protist found in humans and many other animals. Although the clinical relevance of Blastocystis sp. is currently fully unknown for humans, the prevalence of Blastocystis and subtypes are investigated in immunocompetent individuals presenting with symptoms like diarrhea or immunocompromised individuals including cancer patients. In this comprehensive study, the prevalence of Blastocystis sp. and subtypes were investigated in patients (n=94) with different types of malignant solid tumors using PCR targeting SSU rDNA gene and sequencing. All patients were undergoing chemotherapy and had diarrhea. According to obtained results, 46 patients were found to be Blastocystis positive and the molecular prevalence was detected as 48.9%. Among the positive specimens, 43 (43/46; 93.5%) of them were successfully subtyped. ST4 was the most predominant subtype and detected in 24 (55.8%) patients, followed by ST1 (11 patients, 25.6%) and ST3 (8 patients, 18.6%). In the colon cancer group, which had the highest number of patients, Blastocystis sp. was detected with a higher prevalence rate of 61.5% compared with the prevalence rate (48.9%) of all patients. Interestingly, ST3 was not detected in any of this patient group in contrast to ST4 and ST1. In conclusion, high prevalence of the Blastocystis in the immunocompromised patient groups shows the susceptibility of this patient group against any other infectious agents.

Evaluation of Humoral and Cellular Responses in SARS-CoV-2 mRNA Vaccinated Immunocompromised Patients.

BackgroundImmunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.MethodsFive clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination.ResultsAll healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens.ConclusionPatients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

Commentary: Effectiveness of two-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults—nine states, January–September 2021

Embi PJ, Levy ME, Naleway AL, et al. Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults — Nine States, January–September 2021. MMWR Morb Mortal Wkly Rep 2021;70:1553–1559. doi:http://dx.doi.org/10.15585/mmwr.mm7044e3external icon. This month’s selection presents the results of a multicenter study led by the Centers for Disease Control and Prevention evaluating the effectiveness of mRNA COVID-19 vaccines in immunosuppressed adults, including solid organ transplant recipients.1Embi PJ Levy ME Naleway AL et al.Effectiveness of 2-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults - Nine States, January-September 2021.MMWR Morb Mortal Wkly Rep. 2021; 70: 1553-1559Crossref PubMed Google Scholar This study was performed due to several prior reports documenting reduced antibody titers following COVID-19 vaccination in immunosuppressed persons.2Deepak P Kim W Paley MA et al.Effect of Immunosuppression on the Immunogenicity of mRNA vaccines to SARS-CoV-2: a prospective cohort study.Ann Intern Med. 2021; 174: 1572-1585Crossref PubMed Scopus (150) Google Scholar,3Boyarsky BJ Werbel WA Avery RK et al.Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients.JAMA. 2021; 325: 2204-2206Crossref PubMed Scopus (591) Google Scholar The linked report evaluated immunocompetent and immunocompromised adults who were hospitalized with COVID-19 infection at 187 hospitals in nine US states between January and September 2021. Of note, the study only evaluated the effectiveness of a two-dose mRNA vaccine regimen; patients who received only 1 mRNA vaccine dose, ≥3 mRNA vaccine doses, or the Janssen (Johnson & Johnson [Ad26.COV2]) vaccine were excluded. Vaccine effectiveness was determined using a test-negative design, comparing the odds of a positive test result for SARS-CoV-2 between fully vaccinated and unvaccinated patients, after adjusting for patient age, geographic region, calendar time, local virus circulation, and weighting for the inverse propensity to be vaccinated or unvaccinated. The study included 1416 recipients of solid organ or stem cell transplantation, of which 809 (57%) were fully vaccinated with a two-dose mRNA vaccine series. COVID-19-associated hospitalizations were identified among 92 (15%) of the unvaccinated transplant recipients, and 80 (10%) of the fully vaccinated transplant recipients, resulting in an estimated vaccine effectiveness of 59% (95% confidence interval, 38%–73%). The vaccine effectiveness was higher among those who received two Moderna vaccine doses (70%) compared to two Pfizer vaccine doses (45%), although their 95% confidence intervals overlapped, suggesting this difference was not statistically significant. Notably, transplant recipients had the single lowest vaccine effectiveness of all of the immunocompromised patient groups evaluated. The vaccine effectiveness was significantly lower for transplant recipients (compared to immunocompetent individuals) regardless of patient age, mRNA vaccine product, or timing relative to the Delta variant predominance. There are several important limitations of this study, including (1) solid organ transplant recipients and stem cell transplant recipients were evaluated together as a single group, while vaccine effectiveness may be different in these two patient populations, and (2) transplant recipient status was identified by discharge diagnosis codes, rather than manual medical record review or evaluation of medication data. Importantly, however, the study did include a large cohort of transplant recipients across nine different states, and the authors were able to evaluate the impact of mRNA vaccination on an important clinical outcome (namely, COVID-19-associated hospitalization), rather than solely measuring antibody or T cell responses following vaccination. In summary, this report suggests that immunocompromised persons, including solid organ transplant recipients, benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than immunocompetent persons. Transplant recipients, in particular, may be even less protected than other immunocompromised individuals following vaccination. This report underscores the urgent need for further study of the optimal prevention and management of COVID-19 infection focused in the solid organ transplant population.

An initiative to improve pneumococcal immunization counseling in children with nephrotic syndrome.

BackgroundImmunization is essential in preventing life-threatening pneumococcal infections in children with nephrotic syndrome. An additional 23-valent pneumococcal polysaccharide vaccine (PPSV23) series is required for children with nephrotic syndrome. Despite current practice guidelines, many children with nephrotic syndrome do not receive PPSV23.MethodsOur nephrology clinic conducted a quality improvement project to improve the overall rate of PPSV23 counseling to more than 70% within a 12-month period by applying several targeted interventions to raise providers’ awareness, improve communication with primary care providers, and increase provider adherence. Data was collected from the electronic health record (EHR), and monthly performance was tracked via monthly control charts and overall immunization counseling rate charts.ResultsWe increased adherence to PPSV23 vaccination counseling from a baseline of 12 to 86%. The first intervention that effectively increased the vaccine counseling rate from 12 to 30% was improving a provider’s awareness of the PPSV23 literature and vaccine guidelines. Other interventions included regular performance reviews at division meetings, creating an immunization protocol, posting performance charts on the office bulletin board, and unifying vaccine recommendation templates. Lastly, specific and timely EHR reminders improved the total counseling rate from 52 to 86% and maintained adherence until the completion of the project.ConclusionBridging the knowledge gap in provider awareness and using specific EHR reminders can improve adherence to PPSV23 counseling in children with nephrotic syndrome. Such interventions could be applied to similar groups of immunocompromised patients in whom additional vaccines are indicated.Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information. Supplementary InformationThe online version contains supplementary material available at 10.1007/s00467-021-05305-3.

Low Circulating Concentrations of Very Long Chain Saturated Fatty Acids Are Associated with High Risk of Mortality in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2–6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64–0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35–0.82), 0.48 (0.30–0.75), and 0.51 (0.33–0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

The mycological and molecular study of Pneumocystis jiroveci pneumonia among HIV and non-HIV immunocompromised patients hospitalized in pulmonary units in Guilan, Northern Iran

Background and Objectives:Pneumocystis jirovecii pneumonia (PJP) is a serious infection that usually affects those with a weak immune system. Since the prevalence of this infection in Iran and in the world is not clearly defined, the present study aimed to evaluate the incidence, clinical spectrum, and demographic characteristics of PJP among HIV and non-HIV immunocompromised patients.Materials and Methods:Bronchoalveolar Lavage (BAL) specimens were obtained from 3 groups of immunocompromised patients, including acquired immunodeficiency syndrome (AIDS) patients, diabetic patients, and patients receiving immunosuppressive therapies. All were hospitalized in pulmonary units. The specimens were examined using microscopic methods (Giemsa and calcofluor white staining) and the nested-PCR technique based on mtLSU-rRNA gene.Results:A total of 120 BAL samples were collected. From 12.5% (5 from 40) of HIV-infected patients, 5% (2 from 40) of patients receiving immunosuppressive therapies, and 2.5% (1 from 40) of diabetic patients Pneumocystis jiroveci was isolated. There was not any association between the prevalence of PJP and the patient’s gender (p= 0.557) and age (p= 0.681). Fever and dyspnea (n=7, 87.5%), nonproductive cough and abnormal auscultation sound (n=5, 62.5%), and also chills and weight loss (n=2, 25%) were the documented clinical symptoms of PJP. Also, the results showed that none of the samples had positive results for P. jiroveci with microscopic tests while using the nested-PCR method 8 samples had positive results.Conclusion:Since PJP often causes symptoms that are similar to other illnesses, such as the flu or tuberculosis, clinical and laboratory findings should be used simultaneously for making the final decision on drug administration.