Re-vaccination against SARS-COV2 in allogeneic HSCT patients: Repeated primary vaccines doses increases seroconversion rates

Patients undergoing treatment for haematological malignancies have been shown to have reduced antibody responses to vaccination against SARS-COV2. This is particularly important in patients who have undergone allogeneic haemopoietic stem cell transplantation (HSCT), in whom there is limited data about vaccine efficacy. In this retrospective single-centre analysis, we present data on serologic responses following one, two, three or four doses of either Pfizer-BioNTech (PB), AstraZeneca (AZ) or Moderna (MU) SARS-CoV- 2 vaccines from a series of 75 patients who have undergone allogeneic HSCT within 2 years from the time they were revaccinated. The seroconversion rates following post-HSCT vaccination were found to be 50.7%, 78%, 79% and 83% following the first, second, third and fourth primary post -HSCT vaccine doses, respectively. The median time from allograft to first revaccination was 145 days (range 79-700). Our findings suggest that failure to respond to the first SARS-CoV- 2 vaccine post-HSCT was associated with the presence of acute GVHD (p = 0.042) and treatment with rituximab within 12 months of vaccination (p = 0.019). A statistical trend was observed with the presence of chronic GVHD and failure to seroconvert following the second (p = 0.07) and third (p = 0.09) post-HSCT vaccine doses. Patients who had received one or more SARS-CoV- 2 vaccines prior to having an allogeneic stem cell transplant were more likely to demonstrate a positive antibody response following the first dose of revaccination against Sars-CoV- 2 (p = 0.019) and retained this seropositivity following subsequent doses. The incidence of confirmed COVID-19 diagnosis among this cohort at the time of analysis was 16%. 17% of these were hospitalised and there was one recorded death (8%) secondary to COVID-19 in a patient who was 15.7 months post allogeneic transplant. In summary, this study suggests that despite the initial low seroconversion rates observed postallogeneic transplant, increasing levels of antibody response are seen post the second primary vaccine dose. In addition, there seems to be lower risk of mortality secondary to COVID-19 in this vaccinated population, compared to what was reported in the earlier phases of the pandemic prior to use of SARS-COV2 vaccination. This adds support to the widely adopted policy of early full revaccination with repeat of primary vaccine doses and boosters post-HSCT to reduce mortality in this population. Finally, we have identified rituximab use and active GVHD as potential risk factors influencing serological responses to SARS-COV2 vaccination and further work should focus on further characterising this risk and optimum dosing schedule both pre-and post-transplant.

The evolution of a charity support services team

Our charity's mission is dedicated to beating blood cancer by funding research and supporting those affected. Since 1960, we have invested over 500 million in blood cancer research, transforming treatments and saving lives. Since 2015 there has been a Support Services team within the charity. This service was established to provide information that the blood cancer community can trust, in a language they can understand. By connecting and listening to our community they deepen our understanding and help shape our work. Research suggests that blood cancer patients are more likely than any other patients to leave their diagnosis appointment feeling they do not fully understand their condition. Our service can often consolidate the information given by clinicians. Patients also need advice and support on how to adapt to day-to- day life after their diagnosis. There are challenges that are unique to blood cancer, such as living with cancer as a chronic condition, being on 'watch and wait' or fluctuating remissions and relapses. In 2023 the Support Services team have a 7 day presence on our phone line, email and social media platform where people can communicate with one of our trained blood cancer support officers, or one of three Registered Nurses, all who can provide information about blood cancer diagnosis and help with emotional and practical support. We also run an online community forum where people affected by blood cancer can connect, share experiences and provide peer support. The highly experienced haematology nurses provide a clinical aspect to the support of the Blood Cancer Community that enhances the established patient centred support given historically by the charity. The nurses advanced knowledge and experience of haematological cancers, treatments, side effects, holistic care and NHS process can further guide the community. This is in addition to the invaluable information from their treatment teams. In 2023 the Support Services team are now reaching thousands of the blood cancer community. We understand that in the past 3 years the COVID-19 pandemic and the work of our charity around this will have influenced the significant increase in contacts but equally the robust and trusted services provided through this charity has contributed too.

Association of SARS-COV-2 viral RNAemia, IL- 6 gene polymorphism, serum IL-6 and peripheral blood lymphocytes and monocytes with disease severity in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.

Identification Symptoms and Underlying Diseases Related to COVID-19 And Prediction of Death Status Using Artificial Neural Network and Logistic Regression: A Data Mining Approach.

Background and Objectives: Due to the high prevalence of COVID-19 disease and its high mortality rate, it is necessary to identify the symptoms, demographic information and underlying diseases that effectively predict COVID-19 death. Therefore, in this study, we aimed to predict the mortality behavior due to COVID-19 in Khorasan Razavi province. Method(s): This study collected data from 51, 460 patients admitted to the hospitals of Khorasan Razavi province from 25 March 2017 to 12 September 2014. Logistic regression and Neural network methods, including machine learning methods, were used to identify survivors and non-survivors caused by COVID-19. Result(s): Decreased consciousness, cough, PO2 level less than 93%, age, cancer, chronic kidney diseases, fever, headache, smoking status, and chronic blood diseases are the most important predictors of death. The accuracy of the artificial neural network model was 89.90% in the test phase. Also, the sensitivity, specificity and area under the rock curve in this model are equal to 76.14%, 91.99% and 77.65%, respectively. Conclusion(s): Our findings highlight the importance of some demographic information, underlying diseases, and clinical signs in predicting survivors and non-survivors of COVID-19. Also, the neural network model provided high accuracy in prediction. However, medical research in this field will lead to complementary results by using other methods of machine learning and their high power.Copyright © 2022 The Authors.

The temporal evolution in disease phenotype of COVID-19 hospitalisation, intensive care and case fatality rates in cancer patients across the United Kingdom (UKCCP)

Background: People living with cancer are reported to be at increased risk of hospitalization and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is proposed to be dependent on a combination of intrinsic patient and cancer factors such as cancer subtype, and emerging SARS-CoV-2 variants with differing pathogenicity. However, COVID-19 phenotype evolution across the pandemic from 2020 has not yet been systematically evaluated in cancer patients. Method(s): This study is a population-scale real-world evaluation of Coronavirus outcomes in the United Kingdom for cancer patients from 1st November 2020-31st August 2022. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years old. Case-outcome rates, including hospitalization, intensive care and casefatality rates were used to assess the evolution in disease phenotype of COVID-19 in cancer patients. Multivariable logistic regression models were fitted to compare risk of Coronavirus outcomes in the cancer cohort relative to the non-cancer population during the Omicron wave in 2022. Result(s): The cancer cohort comprised of 198,819 positive SARS-CoV-2 tests from 127,322 individual infections. Coronavirus case-outcome rates were evaluated by reference to 18,188,573 positive tests from 15,801,004 individual infections in the non-cancer population. From 2020 to 2022, the SARS-CoV-2 disease phenotype became less severe in both patients with cancer and the non-cancer population, though cancer patients remain at higher risk. In 2022, the relative risk of Coronavirus hospital admission, inpatient hospitalization, intensive care admission and mortality in cancer patients was 3.02x, 2.10x, 2.53x and 2.54x compared to the non-cancer population following multivariable adjustment, respectively. Higher risk of hospital admission and inpatient hospitalization were associated with receipt of B/T cell antibody and/or targeted therapy which also corresponded with an increased risk of Coronavirus mortality. Conclusion(s): The disease phenotype of SARS-CoV-2 in cancer patients in 2022 has evolved significantly from the disease phenotype in 2020. Direct effects of the virus in terms of SARS-CoV-2 hospitalization, intensive care and case fatality rates have fallen significantly over time. However, relative to the general population, people living with cancer and hematological malignancies remain at elevated risk. In order to mitigate the indirect effects of the SARS-CoV-2 pandemic in terms of disruption to cancer care, there should be increased focus on preventative measures. Used in conjunction with vaccination and early treatment programs, this will maximize quality of life for those with cancer during the ongoing pandemic and ensure the best cancer outcomes.

Parameters of coagulation in COVID-19 patients: a correlation with clinical severity

Introduction: COVID-19 infection can be complicated by coagulation derangement and a high risk of thromboembolic episodes. Our study aimedto investigate coagulation parameters in COVID-19 patients and their correlation with clinical severity. Methods: We analyzed coagulation parameters PT, APTT, D-Dimer, and Fibrinogen in 98 RT-PCR-confirmed COVID-19 patients admitted to the Government Institute of Medical Sciences, Gautam Buddha Nagar, Uttar Pradesh, India. Results: This study involved 69 males (70.50%), and 29 (29.5%) were females. The mortality rate was 6.12% (n= 06). Forty-six patients (46.94%) had comorbidities. Thirty-four patients had elevated PT, and 7 had high APTT, whereas D-dimer and fibrinogen levels were raised in 68 and 61 patients, respectively. Among all four parameters, D-Dimer levels were significantly associated with disease severity. Conclusion: Derangement of D-dimer levels is significantly associated with disease severity in COVID-19 infection.

Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Blood derivative therapy

There are three main components manufactured from whole blood: red blood cells (RBCs), plasma, and platelets. Plasma contains a multitude of different proteins, peptides, and biologic substances. Approximately 53 million liters of plasma was collected in the United States in 2019. Following collection, plasma is frozen and manufactured into plasma-derived medicinal products (PDMPs). During the manufacture process, several thousand plasma units are pooled for Cohn fractionation, which is based upon cold ethanol precipitation of proteins. The PDMPs are further prepared using ion exchange or affinity chromatography and additional steps to inactivate and remove infectious diseases such as viruses. Almost 20 different therapeutic plasma proteins are purified from plasma via these multi-step manufacturing processes. Interestingly, the demand for pharmaceutical plasma products, particularly intravenous immunoglobulin (IVIG) products, has been increasing. The manufacture and therapeutic role of blood derivatives particularly immunoglobulin therapy, Rh immunoglobulin (RhIG), COVID-19 convalescent plasma (CCP) and hyperimmune globulins, albumin, clotting factors, fibrin sealants, and platelet rich plasma will be described.Copyright © 2022 AME Publishing Company. All Rights Reserved.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

Burden of respiratory coinfections in haematology patients with COVID-19

Introduction: Following the lifting of generalised restrictions and universal masking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2)- infected patients, especially the clinically extremely vulnerable (CEV) haematology patients, are at an increased risk for other respiratory viral coinfections;therefore, physicians need to be cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV- 2 and other respiratory pathogens in patients with haematological cancers presenting to a large tertiary care hospital. Method(s): From July 2022-December 2022, patients with haematological disorders were screened for SARS-CoV- 2 and other 10 common respiratory pathogens by PCR. We performed a retrospective analysis of patients with concurrent respiratory viruses and will prospectively evaluate the same from Jan 2023 to March 2023. Result(s): During this period a total of 322 inpatients had routine screening and additional 6213 swabs were done in the outpatient/ambulatory setting, of which 294 were positive in 221 patients. We excluded all patients who had a single positive PCR swab result and specifically analysed only patients with coinfections. We identified 30 patients (14%) who had respiratory coinfections with 73 viral infections/reactivations over 6 months period, which represented 25% of all positive swabs: 25 inpatients (19 symptomatic/6 asymptomatic) and 48 in outpatients (32 symptomatic/16 asymptomatic). The median age of the cohort was 47.3 years (21-77). Patients were post allograft (n = 15), autograft (n = 7), post CART (n = 5) and postchemotherapy (n = 4). Of the 30 cases, 13 patients had concurrent infections: 5 SARS-CoV2, 10 Respiratory syncytial virus (RSV), 7 Rhino and 4 Influenza A, with all patients having dual viral infection. The remaining 17 patients had multiple viral infections but separated by a median of 54 days (range 27-137 days): 16 SARS-CoV2, 5 RSV, 6 Rhino, 2 Parainfluenza, 2 Adeno and one each of Influenza A, Influenza B, and metapneumovirus. Of the treatable infections (n = 46), 22% were detected on routine asymptomatic swabbing, with 50% of SARS-CoV2 detected on routine swabs. All 8 patients with Influenza were treated with oseltamivir, of 16 RSV cases one was treated with oral ribavirin and of the 22 SARS-CoV2 patients, 5 were treated (4 Paxlovid and 1 Remdesivir). No patients needed intensive care support and no deaths were reported. Conclusion(s): The burden of respiratory coinfections in CEV cohort has a significant impact on respiratory isolation and management, including appropriate & timely initiation of therapy for treatable viral infections. Although mortality was not increased secondary to respiratory coinfections and none needed intensive care, larger prospective cohorts are needed to assess the exact impact.

COVID-19 pre-exposure prophylaxis with tixagevimab/cilgavimab in patients with haematological malignancy: A single-centre experience

Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

SeroNet Pooling Project of immunocompromised populations

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.

Evusheld prophylaxis increases social interactions and improves anxiety, depression, agoraphobia and quality of life scores

Evusheld is a combination injection of tixagevimab/cilgavimab for pre-exposure COVID-19 prophylaxis and was made available to UK private clinics from October 2022. NICE review is ongoing. Whilst efficacy analysis of Evusheld has focused on the risk-reduction of contracting COVID-19, anecdotal reports suggest additional psychological benefits from Evusheld, although supportive objective data are lacking. In this study, we used 4 well-established psychological health questionnaires to assess different psychological parameters (EQ5D-3 L quality of life (QoL) score, DSM5 Agoraphobia score, Duke's Social Support Index (DSSI) and the hospital anxiety and depression score (HADS)) in blood cancer patients treated with Evusheld at the Genesis Care (GC) Clinic, Cambridge. Patient data (pre-and post-Evusheld) were compared with a control group of GC blood cancer patients who had not received Evusheld. The study was approved by GC and all patients had consented to email contact. Questionnaire replies were anonymised and free-text comments were invited. Questionnaires were completed by 29/40 Evusheld and 54/100 control patients. With EQ5D, Evusheld did not impact mobility, self-care and pain/discomfort scores and patient/ control groups scored at similar levels. EQ5D scores for 'usual activities' and 'anxiety/depression' improved post-Evusheld (patients reporting 'normal activities' increased from 52% to 76% (control = 78%);patients reporting 'no anxiety/ depression' increased from 45% to 66% (control = 65%)). The mean global EQ5D QoL score improved post-Evusheld [69.4% to 72.9% (control = 75.7%)]. With the DSM5 agoraphobia score, Evusheld treatment improved agoraphobia parameters, reducing the mean score from 15.7 to 5.1 (control = 3.7;max = 40) with certain striking changes;72% of pretreatment patients avoided crowded situations all of/most of the time, reducing to 14% post-Evusheld (control = 11%). The DSSI score assessed social/work interactions with external household contacts and post-Evusheld the mean number of interactions over 3 weeks increased from 1.48 to 3.37 (control = 3.77). Pre-Evusheld, 52% of patients had no interactions outside their household, dropping to 20% in the 3 weeks post-Evusheld (control = 17%). Using the HADS 14-point analysis of depression and anxiety revealed on average that each parameter was 25.3% 'significantly improved' and 25.4% 'a little improved' post-Evusheld. Accepting limitations of a small study and potential biases associated with a self-funding patient cohort, Evusheld treatment broadly improved all psychological scores assessed. Free-text comments clearly indicate that Evusheld had a major positive impact on QoL/social mobility for specific patients. The Evusheld patients had higher baseline scores for social isolation, anxiety, depression and agoraphobia compared with control patients, yet Evusheld treatment appeared to improve these parameters to a level similar to control patients.

Evusheld Prophylaxis Improves Social Interactions, Anxiety, Depression, Agoraphobia, and Quality of Life in Blood Cancer Patients

Evusheld is a combination injection of tixagevimab and cilgavimab and is indicated for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older. Its use has been advocated for immunosuppressed individuals, such as blood cancer patients, although uptake varies significantly between countries. Despite extensive use internationally, there has been limited analysis of potential psychological benefits that vulnerable patients might gain from receiving this prophylactic medication. In this study we have quantified four key psychological health parameters in blood cancer patients who received Evusheld (EQ5D-3L quality of life score, DSM5 Agoraphobia score, Duke's Social Support Index and the hospital anxiety and depression score) and compared their responses with a control group of patients who did not receive Evusheld. We show that patients who opted for treatment had higher baseline markers of psychological stress and ill-health compared with non-treated individuals but that treatment with Evusheld significantly improved the psychological health of recipients and increased the level of physical social/work interactions over that of control patients. Although there are limitations with this small study, the findings strongly suggest that Evusheld prophylaxis can provide significant psychological benefits for vulnerable blood cancer patients who have significant anxiety about COVID-19 infection. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Outcomes of cancer patients with Covid-19 admitted to the Intensive Care Unit: A retrospective study

Introduction: Active cancer increases the odds of death among patients with COVID-19.1 Cancer patients may be at increased risk of complications and mortality from COVID-19 owing to the systemic effects of malignancy, immune suppression after chemotherapy, treatment-related complications and presence of co-morbidities.2 They may develop serious complications necessitating ICU admission. In a meta-analysis, the pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2%.3 Our hospital is a tertiary referral cancer centre, and the ICU admitted cancer patients with Covid-19 throughout the pandemic. Objective(s): To determine the 30-day in-hospital mortality of adult cancer patients with Covid-19 admitted to the ICU. We also aimed to determine the factors associated with mortality in cancer patients with Covid-19. Method(s): After approval from the Institutional Ethics Committee, data of all cancer patients (age = 16 years) with Covid-19 admitted to the ICU between March 2020 and March 2021 were retrieved from the hospital records. In case of multiple ICU admissions, data from the first admission was recorded. Data recorded included demographic details, type of cancer (solid, haematological), surgical status, APACHE-II and SOFA scores, C-reactive protein, and interventions in ICU. The primary outcome was 30-day in-hospital mortality. Data were analysed using Man-Whitney test and chi-square test. A multivariable regression analysis was carried out to determine factors associated with mortality. Result(s): Data of 127 cancer patients with Covid-19 was analysed. The median [interquartile range, IQR] age was 55 (43-62) years, and there were 50 females (39.3%). Comorbidities were present in 46 (36%) patients, the commonest being diabetes (29 patients) and hypertension (31 patients). The median [IQR] APACHE-II and SOFA scores were 15[8-20] and 4[2-7], respectively. Overall, 62/127 patients died, and 30-day hospital mortality was 49%. There were 30 patients with haematological malignancy and 97 with solid tumours with 30-day in-hospital mortality rates of 46.7% and 49.5%, respectively;p = 0.84). Amongst patients with solid tumours, there was no difference in mortality in surgical patients compared to non-surgical patients (43.3% vs. 52.2%;p = 0.42). Table 1 summarises the parameters and interventions in survivors and non-survivors. On multivariable analysis, only the change in SOFA score from Day 1 to Day 3 was independently associated with outcome (Odds ratio 1.36 (95% confidence interval 1.01-1.84, p-0.04). Conclusion(s): In patients with cancer and Covid-19 and age =16 years admitted to our ICU, the crude 30-day hospital mortality was 47%. There was no association of mortality with cancer type or surgical status. The only independent predictor of mortality was progression of organ failure. Cancer patients with Covid-19 have a reasonable outcome and should be given a trial of intensive care.

Experiences of patients from minority ethnic backgrounds in the stem cell transplant pathway during COVID-19

Background: Stem cell transplantation is a potentially life-saving intervention for patients with blood cancer. Research suggests that there are existing disparities in access, care and treatment experiences, with patients identifying with a minority ethnic heritage reporting greater disadvantage compared to patients from white British, Irish or Northern European backgrounds. Although we know that the COVID-19 pandemic has been challenging for patients, less is known about the experiences of patients from specific ethnic communities. Method(s): In this research, we undertook 1-1, semi-structured interviews with eight patients within the stem cell transplant pathway who identify with a minority ethnic background. Interviews took place online, between May and November 2021. The interview questions explored views on aspects of the pandemic, including access and experience of care delivery, intervention, mental health and financial impact. Interviews were transcribed verbatim and analysed using reflexive thematic analysis. Result(s): The majority of patient participants were female (75%), and identified with a Black African or Caribbean heritage (75%). Four themes were identified from the data: (1) 'Lack of suitable donors' described the challenges of finding a stem cell donor and the importance of raising awareness of stem cell donation specifically within minority ethnic communities;(2) 'Experiences of care' explored patients' experiences of the healthcare system from pre-diagnosis to post-treatment, including how the COVID-19 pandemic had made some aspects of care easier but acted to disrupt others;(3) 'Intense and unpredictable process' described the nature of living with blood cancer and how this has impacted upon patients' lives including the extent to which they had been able to access and make use of advice to help keep them safe during the pandemic;and (4) 'Coping mechanisms' identified the factors which helped patients' to understand and adjust to living with their diagnosis and the treatment process. Conclusion(s): Patients in the stem cell transplant pathway often experience intense treatment regimens, debilitating symptoms and long hospital stays, which has a significant impact on their lives. Minority ethnic patients describe facing additional challenges in relation to health inequalities both within and outside of the pandemic. Seeking support from family, peers or community organisations can help buffer the negative impacts of living with blood cancer and multiple disadvantages, but such support was more difficult to access during the pandemic. This had psychological consequences for patients who are already within an intense emotional journey. Pandemic recovery plans should address mental health support as a priority.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Expansion of human T cells using xenogeneic free and gamma irradiated human platelet lysate

Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumorassociated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells.