COVID-19 Antibody Seroconversion in Cancer Patients: Impact of Therapy Cessation-A Single-Center Study.

BACKGROUND: The effective development of COVID-19 vaccination has mitigated its harm. Using two laboratory methods, we investigated the efficacy of the BNT162b2 mRNA and BBIBP-CorV COVID-19 vaccines on seroconversion rates in cancer patients undergoing active cancer treatment. METHODS: SARS-CoV-2 vaccines were scheduled for 134 individuals. The consenting participants submitted three venous blood samples. Three samples: T0, T1, and T2. The ABBOTT-SARS-CoV-2 IgG II Quant and Elecsys® Anti-SARS-CoV-2 assays were used to evaluate the samples and convert the antibody titers to WHO (BAU)/mL units. RESULTS: Cancer patients exhibited a higher seroconversion rate at T2, regardless of vaccination type, and the mean antibody titers at T1 and T2 were higher than those at T0. BBIBP-CorV patients required a booster because BNT162b2 showed a higher seroconversion rate between T0 and T1. Statistics indicate that comparing Abbott and Roche quantitative antibody results without considering the sample collection time is inaccurate. CONCLUSIONS: COVID-19 vaccines can still induce a humoral immune response in patients undergoing cancer-targeted therapy. The strength of this study is the long-term monitoring of antibody levels after vaccination in cancer patients on active therapy using two different immunoassays. Further multicenter studies with a larger number of patients are required to validate these findings.

QuantiFERON-CMV and monitor predict cytomegalovirus, mortality, and graft-versus-host disease in transplant recipients.

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

Comparative Assessment of the Kinetics of Cellular and Humoral Immune Responses to COVID-19 Vaccination in Cancer Patients.

OBJECTIVE: The kinetics of immune responses to various SARS-CoV-2 vaccines in cancer patients were investigated. METHODS: In total, 57 cancer patients who received BNT162b2-RNA or BBIBP-CorV vaccines were enrolled. Cellular and humoral immunity were assessed at three-time points, before the first vaccine dose and 14-21 days after the first and second doses. Chemiluminescent microparticle immunoassay was used to evaluate SARS-CoV-2 anti-spike IgG response, and QuantiFERON® SARS-CoV-2 kit assessed T-cell response. RESULTS: Data showed that cancer patients' CD4+ and CD8+ T cell-median IFN-γ secretion of SARS-CoV-2 antigens increased after the first and second vaccine doses (p = 0.027 and p = 0.042). BNT162b2 vaccinees had significantly higher IFN-γ levels to CD4+ and CD8+ T cell epitopes than BBIBP-CorV vaccinees (p = 0.028). There was a positive correlation between IgG antibody titer and T cell response regardless of vaccine type (p < 0.05). CONCLUSIONS: This study is one of the first to investigate cellular and humoral immune responses to SARS-CoV-2 immunization in cancer patients on active therapy after each vaccine dose. COVID-19 immunizations helped cancer patients develop an effective immune response. Understanding the cellular and humoral immune response to COVID-19 in cancer patients undergoing active treatment is necessary to improve vaccines and avoid future SARS pandemics.

Non-Dexamethasone Corticosteroid Therapy's Effect on COVID-19 Prognosis in Cancer Patients: A Retrospective Study.

BACKGROUND: Anti-inflammatory corticosteroids are used in cancer treatment and COVID-19 infections. Data on the impact of non-dexamethasone corticosteroids on COVID-19 infection severity in cancer patients are minimal. This study investigates if corticosteroid treatment affects the disease severity in adult cancer patients. METHODS: A total of 116 COVID-19-infected cancer patients on hydrocortisone (H) or prednisone (P) were compared to 343 untreated patients. The study included patients who received corticosteroids before (B), after (A), or both before and after (B and A) COVID-19 infections. Ventilation support, hospitalization and mortality were investigated. RESULTS: Our data showed that a significantly greater number of patients taking H or P required ventilation support and hospitalization and that mortality rates were higher than the control group. Patients who received H or P after COVID-19 infection had a significantly worse prognosis than the other sub-groups and the control group. CONCLUSION: Corticosteroids impacted cancer patients' COVID-19 prognosis. Despite the limited sample size, H- and P-treated patients' corticosteroids performed worse than the control, especially if treatments were received after COVID-19 infection. Hence, when a cancer patient already on H or P treatment is diagnosed with COVID-19, we recommend switching to a steroid treatment as suggested by international guidelines.

The Effect of Dexamethasone Treatment on COVID-19 Prognosis in Cancer Patients.

Background: Dexamethasone is used to treat cancer, relieve chemotherapy-induced nausea and vomiting, enhance cancer patients' appetites, and treat COVID-19 patients. There is little evidence of the impact of a dexamethasone treatment plan on the severity of COVID-19 infections in cancer patients. This study explores whether dexamethasone treatment plan influences the severity of COVID-19 in dexamethasone-treated cancer patients. Methods: The medical records of 108 cancer patients receiving dexamethasone at King Hussein Cancer Center with a COVID-19 infection and 343 without corticosteroid treatment were reviewed. Patients on dexamethasone within seven days before infection, after infection, or both were included. Ventilation support, hospitalization, and mortality within 28 days of a COVID-19 diagnosis were key severity factors. Results: We found that dexamethasone before a COVID-19 infection increased the risk of requiring ventilation assistance and mortality within 28 days by a factor of 5.8 (2.8−12.0) relative to control (p < 0.005). Continuing dexamethasone treatment after a COVID-19 infection, or starting it after infection, had a risk factor equivalent to control. Conclusion: Our data showed that dexamethasone therapy protocol affected COVID-19 prognoses in cancer patients, and it is preferable to not discontinue therapy after infection. A rigorous prospective comparison between early and late dexamethasone dosing is needed to determine the best protocol for treatment.

An update on the impact of SARS-CoV-2 pandemic public awareness on cancer patients' COVID-19 vaccine compliance: Outcomes and recommendations.

Background: Aside from the pandemic's negative health effects, the world was confronted with public confusion since proper communication and favorable decisions became an ongoing challenge. As a result, the public's perceptions were influenced by what they knew, the many sources of COVID-19 information, and how they interpreted it. With cancer patients continuing to oppose COVID-19 vaccines, we sought to investigate the COVID-19 pandemic and vaccine sources of this information in adult cancer patients, which either helped or prevented them from taking the vaccine. We also assessed the relevance and impact of their oncologists' recommendations in encouraging them to take the vaccine. Methods: From June to October 2021, an online survey was conducted at King Hussein Cancer Center. A total of 441 adult cancer patients took part in the study. Patients who had granted their consent were requested to complete an online questionnaire, which was collected using the SurveyMonkey questionnaire online platform. Descriptive analysis was done for all variables. The association between categorical and continuous variables was assessed using the Pearson Chi-square and Fisher Exact. Results: Our results showed that 75% of the patients registered for the COVID-19 vaccine, while 12% refused vaccination. The majority of participants acquired their information from news and television shows, whereas (138/441) got their information through World Health Organization websites. Because the SARS-CoV-2 vaccines were made in such a short period, 54.7 % assumed the vaccines were unsafe. Only 49% of the patients said their oncologists had informed them about the benefits of SARS-CoV-2 vaccines. Conclusions: We found that SARS-CoV-2 vaccine hesitancy in cancer patients might be related to misinformation obtained from social media despite the availability of supportive scientific information on the vaccine's benefits from the physicians. To combat misleading and unreliable social media news, we recommend that physicians use telehealth technology to reach out to their patients in addition to their face-to-face consultation, which delivers comprehensive, clear, and high-quality digital services that guide and help patients to better understand the advantages of COVID-19 vaccines.

Establishing the First COVID-19 Convalescent Plasma Biobank in Jordan.

Background: Antibodies with the specialized ability to fight infection can be found in the blood of individuals who have recovered from or have been vaccinated against COVID-19. As a result, plasma from these individuals could be used to treat critically ill patients. This treatment is known as convalescent plasma (CCP) therapy. Methods: Plasma units from 1555 consented healthy blood bank donors were collected from February to September 2021. Blood units were tested for the quantitative determination of Immunoglobulin G (IgG) antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus using one of the following assays based on the availability of the kits: The LIAISON® SARS-CoV-2 TrimericS IgG assay or the Abbott SARS-CoV-2 IgG II Quant assay. Results: Among the tested donors, 1027 participants tested positive for neutralizing anti-SARS-CoV-2 IgG antibodies (66.04%). There were 484 donors whose plasma qualified to be used for CCP therapy (47.13%) and 214 CCP units were stored in the COVID-19 convalescent biobank. Conclusion: We were able to identify and store 214 fresh frozen plasma units qualified for CCP-plasma therapy for COVID-19 patients according to World Health Organization standards. Hence, we established the first COVID-19-convalescent plasma data and plasma biobank for treating COVID-19-infected cancer patients in Jordan and the region.

Comparison of the Immunogenicity and Protective Efficacy of Various SARS-CoV-2 Vaccines among Healthcare Workers: Are Our White Coat Armies Protected?

Background: The effective immunization of healthcare workers (HCWs) plays a vital role in preventing the spread of SARS-CoV-2 infection during the coronavirus disease 2019 (COVID-19) pandemic. There is limited data on the immune response to vaccination among HCWs. We aim to determine seroprevalence rates and neutralizing IgG antibody response to various immunizations among HCWs. Methods: This study was conducted between July and September 2021, in which blood samples were obtained from HCWs and SARS-CoV-2 IgG neutralizing antibodies were measured. Data regarding vaccination status with Pfizer/BioNTech, Sinopharm, or AstraZeneca vaccines, occupation, and prior COVID-19 infection were analyzed. Results: COVID-19 infection post-vaccination was associated with higher mean antibody titers, regardless of vaccine type. Pfizer/BioNTech vaccination produced higher mean antibody titers for HCWs with prior COVID-19 infection (p < 0.00001) than other types of vaccines. Although 96% of HCWs were vaccinated, 3% were seronegative. For HCWs who were seropositive, there were no significant differences between the mean antibody titers when comparing occupations and blood indices. Conclusion: Awareness of the immunity status of HCWs is key to protecting this important group against SARS-CoV-2, especially those without prior COVID-19 infection. Further public health efforts regarding booster vaccination for HCWs are crucial to provide necessary antibody protection.

Changing trends in seroprevalence rates of transfusion-transmitted diseases among blood donors in Jordan.

BACKGROUND: Hepatitis B and C infections and transmission are a serious challenge to all healthcare systems. We studied seroprevalence rates of Transfusion Transmitted Diseases (TTD) among blood bank donors in Jordan from 2014 to 2019 as a follow-up study of our previously published work. In addition, we wanted to explore the efficacy of the mandatory vaccination of infants against hepatitis B virus (HBV) which was implemented by the Ministry of Health since 1995 for the eradication of HBV infection in Jordan. METHODS: We reviewed blood bank donors' records at King Hussein Cancer Center (KHCC) from January 1st, 2014, until December 31st, 2019. Results of seropositivity prevalence rates for HBsAg, anti-HBcore, and anti-HCV, using Enzyme-Linked ImmunoSorbent Assay (ELISA) were compared to seropositivity rates from our previously published data. In addition, our results were compared to data obtained from other blood banks in Jordan, as well as compared to published information from blood banks in neighboring countries. RESULTS: The prevalence rates (%) of seropositive blood donors for viral hepatitis for the years 2014, 2015, 2016, 2017, 2018, and 2019, were as follows: HBsAg rates were 0.3386, 0.2108, 0.1801, 0.1898, 0.2068, and 0.2741; anti-HBcore rates were 4.1112, 3.2271, 2.9748, 2.8405, 2.6879 and 3.0986; and anti-HCV rates were 0.1129, 0.0486, 0.0548, 0.0654, 0.0782, and 0.0839, respectively. There was a significant increase in the prevalence of HBsAg, Anti-HBcore and Anti-HCV antibodies in 2019 (one sample z-score test, p < 0.00001). CONCLUSIONS: Prevalence rates of hepatitis B and C infections among Jordanian blood bank donors showed a steady decline between 2009 and 2017, and these rates were much lower in Jordan than in neighboring countries. However, an increase in the prevalence rates of hepatitis B and C infections among blood bank donors was documented in 2019. While the reasons for this increase are not clear yet, these findings highlight the importance of renewed efforts to increase public health awareness of HBV and implement effective measures to prevent the transmission and infection with HBV, including national vaccination programs.

Dramatic rise in seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors: The evolution of a pandemic.

BACKGROUND: Seroprevalence studies of SARS-CoV-2 antibodies are useful in assessing the epidemiological status in the community, and the degree of spread. OBJECTIVE: To study the seroprevalence rates of SARS-CoV-2 antibodies among healthy blood donors in Jordan, at various points of time and as the pandemic evolves in the community. METHODS: In total, 1374 blood donor samples, from three groups, were tested for SARS-CoV-2 total immunoglobulin antibodies. In the first group, samples from 734 individuals (from donations made between January and June 2020) were tested in June. In the second group, 348 individuals were tested in September 2020. The third group of 292 individuals was tested in February 2021. A qualitative assay was used for testing (specificity 99.8%, sensitivity 100%). RESULTS: The first two groups, from January-June and September 2020, when confirmed Covid-19 cases numbered between several hundred and 3000, showed a seroprevalence rate of 0% (95% CI 0.00-0.51%). The third group (early February 2021), when the number of confirmed cases had reached 100 times that of September 2020, revealed a seroprevalence of 27.4% (95% CI 22.5-32.9%). CONCLUSIONS: A dramatic rise in seroprevalence of SARS-CoV-2 antibodies was seen among healthy blood donors in Jordan, in parallel with widespread intracommunity transmission of the disease. This information is useful for assessing the degree of herd immunity, and provides for better understanding of the pandemic.

Seroprevalence rates of transfusion-transmitted infections among blood donors in Jordan.

INTRODUCTION: Statistics on the prevalence of donor screening for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in Jordan are outdated. There are no studies on the prevalence of anti-HIV I/II, anti-human T-cell lymphotropic virus type I and II (anti-HTLV-I/II), or anti-syphilis. Data are also lacking on the prevalence and significance of using anti-HBc screening in Jordan. This study aimed to evaluate the prevalence of transfusion-transmissible infections (TTI) among donors at King Hussein Cancer Center and compare it with neighboring countries and to evaluate the significance of screening for anti-HB core total (anti-HBc) antibodies. METHODOLOGY: A retrospective analysis covering the period from 2009 to 2013 was conducted on records of healthy donors. The number of donors was 10,101, 12,694, 13,387, 14,256, and 12,495, respectively. Donors were screened for HBsAg, anti-HBc, anti-HIV I/II, anti-HCV, and anti-HTLV-I/II using ELISA technique, while syphilis antibodies were detected using rapid chromatographic immunoassay. RESULTS: Among 62,933 donors, the prevalence of HBsAg was 0.52%, of anti-HBc was 6.04%, and of anti-HCV was 0.16%. None of the donors were positive for anti-HIV I/II, anti-HTLV I/II, or anti-TP. CONCLUSIONS: This study demonstrates that the seroprevalence for HBsAg, anti-HBc, and anti-HCV in Jordan was low compared to neighboring countries. None of the donors were confirmed positive for anti-HIV I/II, anti-HTLV I/II, or anti-TP during the studied period. This study demonstrates the importance of screening for anti-HBc to improve blood and platelet safety and stresses the need to complement it with an algorithm that qualifies reentry of anti-HBc false-positive donors.

Establishing an Iso-Compliant Modern Cancer-Biobank in a Developing Country: A Model for International Cooperation.

King Hussein Cancer (KHCC) is a specialized cancer center that treats both adult and pediatric cancer patients from Jordan and the neighboring countries. KHCC is acknowledged as a leader in cancer treatment in the Middle East and its vision is to maintain its leading position in cancer therapy and research. Hence, KHCC embarked on establishing the first ISO compliant cancer biobank (KHCCBIO) in Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC wanted to change this situation by establishing an ISO-compliant cancer biobank which would incorporate all current international guidelines and best-in class practices under an approved quality management system for the benefit of researchers in Jordan, its neighboring countries, and throughout the world. The established biobank would follow the highest ethical standards in collecting, processing, storing and distributing high-quality, clinically annotated biospecimens.The strategy used in establishing KHCCBIO was based on taking advantage of international networking and collaboration. This in essence led to knowledge transfer between well established organizations, institutions and individuals from Europe and Jordan, in existing technological innovation and internationally recognized quality standards. KHCC efforts were facilitated by a grant from the European Union under the seventh frame work program.Future aims of KHCCBIO are to develop KHCC's research infrastructure, increase its scope and visibility and improve its competitiveness throughout the biomedical science arena. Moreover, KHCCBIO is aiming to establish a platform for future knowledge transfer and collaborative research; develop partnerships between European and Middle Eastern organizations.

The establishment of an ISO compliant cancer biobank for Jordan and its neighboring countries through knowledge transfer and training.

Research studies aimed at advancing cancer prevention, diagnosis, and treatment depend on a number of key resources, including a ready supply of high-quality annotated biospecimens from diverse ethnic populations that can be used to test new drugs, assess the validity of prognostic biomarkers, and develop tailor-made therapies. In November 2011, KHCCBIO was established at the King Hussein Cancer Center (KHCC) with the support of Seventh Framework Programme (FP7) funding from the European Union (khccbio.khcc.jo). KHCCBIO was developed for the purpose of achieving an ISO accredited cancer biobank through the collection, processing, and preservation of high-quality, clinically annotated biospecimens from consenting cancer patients, making it the first cancer biobank of its kind in Jordan. The establishment of a state-of-the-art, standardized biospecimen repository of matched normal and lung tumor tissue, in addition to blood components such as serum, plasma, and white blood cells, was achieved through the support and experience of its European partners, Trinity College Dublin, Biostór Ireland, and accelopment AG. To date, KHCCBIO along with its partners, have worked closely in establishing an ISO Quality Management System (QMS) under which the biobank will operate. A Quality Policy Manual, Validation, and Training plan have been developed in addition to the development of standard operating procedures (SOPs) for consenting policies on ethical issues, data privacy, confidentiality, and biobanking bylaws. SOPs have also been drafted according to best international practices and implemented for the donation, procurement, processing, testing, preservation, storage, and distribution of tissues and blood samples from lung cancer patients, which will form the basis for the procurement of other cancer types. KHCCBIO will be the first ISO accredited cancer biobank from a diverse ethnic Middle Eastern and North African population. It will provide a unique and valuable resource of high-quality human biospecimens and anonymized clinicopathological data to the cancer research communities world-wide.

A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo.

A major goal of treatment strategies for cancer is the development of agents which can block primary tumor growth and development as well as the progression of tumor metastasis without any treatment associated side effects. Using mini peptide display (MPD) technology, we generated peptides that can bind to the human vascular endothelial growth factor (VEGF) receptor KDR. These peptides were evaluated for their ability to block angiogenesis, tumor growth and metastasis in vitro and in vivo. A D-amino acid peptide with high serum stability (ST100,059) was found to have the most potent activity in vitro as indicated by inhibition of VEGF stimulation of endothelial cells. It was also found to be the most active of the series in blocking VEGF-mediated activity in vivo, as measured in Matrigel-filled angioreactors implanted in mice. ST100,059 blocks VEGF-induced MAPK phosphorylation, as well as inhibits VEGF-induced changes in gene expression in HUVEC cells. In in vivo studies, treatment of female C57BL/6 mice inoculated with B16 mouse melanoma cells with ST100,059 resulted in a dose-dependent decrease in tumor volume and lung metastasis as compared to control groups of animals receiving vehicle alone. These studies demonstrate that by using MPD, peptides can be identified with enhanced affinity relative to those discovered using phage display. Based on these studies we have identified one such peptide ST100,059 which can effectively block tumor growth and metastasis due to its anti-angiogenic effects and ability to block intracellular signaling pathways involved in tumor progression.

Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo.

Imatinib mesylate (STI571, imatinib) inhibited DNA synthesis in primary human T cells stimulated with allogeneic mature dendritic cells or phytohemagglutinin (PHA) but did not induce apoptosis. The values for the concentration that inhibits 50% (IC50) of T-cell proliferation stimulated by dendritic cells and PHA were 3.9 microM and 2.9 microM, respectively, that is, within the concentration range found in patients treated with imatinib mesylate. Interestingly, imatinib mesylate did not inhibit expression of T-cell activation markers CD25 and CD69, although it reduced the levels of activated nuclear factor-kappaB (NF-kappaB) and changed phosphorylation or protein levels of Lck, ERK1/2, retinoblastoma protein, and cyclin D3. When T cells were washed free of imatinib mesylate, they proliferated in response to PHA, demonstrating that inhibition is reversible. Treatment with imatinib mesylate led to accumulation of the cells in G0/G1 phase of the cell cycle. The in vitro observations were confirmed in vivo in a murine model of delayed-type hypersensitivity (DTH). In mice treated with imatinib mesylate, DTH was reduced in comparison to sham-injected controls. However, the number of splenic T cells was not reduced showing that, similarly to in vitro observations, imatinib mesylate inhibited T-cell response, but did not cause apoptosis. These findings indicate that long-term administration of high-dose imatinib mesylate might affect immunity.

Complete Freund's adjuvant immunization prolongs survival in experimental prion disease in mice.

We recently reported that immunization of mice with certain self-prion protein peptides induced specific T-cell and B-cell immune responses; importantly, this immunization was associated with a decrease in the number of protease-resistant PrP(Sc) particles recoverable in a transplanted, scrapie-infected syngeneic tumor. The present study was carried out to determine whether immunization with the immunogenic PrP peptides might influence the natural history of experimental scrapie in mice. We immunized C57BL/6 mice with self-prion peptides in complete Freund's adjuvant (CFA) or with CFA alone as a control and then infected the mice with mouse-adapted scrapie by injection either intraperitoneally or intracerebrally. We report here that immunization with CFA, irrespective of whether prion peptides were present in the inoculum, resulted in marked prolongation of survival of the mice, whether the challenge was intracerebral or intraperitoneal. Mice in the immunized and control groups that died contained equivalent amounts of PrP(Sc). Thus, CFA immunization has a therapeutic effect in experimental scrapie in mice, possibly by reducing the rate of PrP(Sc) accumulation in the brain.