A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Evaluation of COVID-19 Vaccines in Primary Prevention Against Infections and Reduction in Severity of Illness Following the Outbreak of Sars-Cov-2 Omicron Variant in Shanghai

Objectives: To evaluate COVID-19 vaccines in primary prevention against infections and lessening the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai. Method(s): To investigate whether inactivated vaccines were effective in protecting against COVID-19 infections, we estimated the odds ratio (OR) of the vaccination in COVID-19 cases vs. matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied the multivariate stepwise Logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors. Result(s): Out of the 153,544 COVID-19 patients included in the analysis, 118,124 (76.9%) patients had been vaccinated and 143,225(93.3%) were asymptomatic patients. Of the 10,319 symptomatic patients, 10,031(97.2%), 281(2.7%) and 7(0.1%) experienced mild, moderate, and severe infections, respectively. There is no evidence that the vaccination helped protect from infections (OR=0.82, p=0.613). The vaccination, however, offered a small but significant protection against symptomatic infections (RR=0.92, p < 0.001) and halved the risk of moderate/severe infections (OR=0.48, 95% CI: 0.37 - 0.61). Older age (> 60 years) and malignant tumors were significantly associated with moderate/severe infections. Gender also appeared to be a risk factor for symptomatic infections, with females being associated with a lower risk for moderate/severe illness. Conclusion(s): Inactivated COVID-19 vaccines helped provide a small but significant protection against symptomatic infections and halved risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking COVID-19 Omicron variant community spread.Copyright © 2023

A New Registry for Genetic Diagnosis of Inborn Errors of Immunity within the Military Health System

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Uptake of vaccination in older Indian patients with cancer: A cross-sectional observational study

Background: Older patients with cancer are at a higher risk of invasive infections. Vaccination is an effective approach to decrease the mortality and morbidity associated with infections. Objective(s): Our primary objective was to evaluate the proportion of older patients with cancer who had received routine vaccinations against pneumococcal, influenza, and coronavirus disease 2019 (COVID-19). Our secondary objective was to identify the factors associated with vaccine uptake such as age, sex, education, marital status, comorbidities, and place of residence. Material(s) and Method(s): This cross-sectional observational study was conducted in the geriatric oncology outpatient clinic of the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary care cancer hospital in Mumbai, India, from February 2020 to January 2023. We included all patients aged >=60 years who were evaluated in the geriatric oncology clinic during the study period and for whom the immunization details were available. The uptake of COVID-19 vaccine was calculated from March 2021 onwards, which was when the COVID-19 vaccine became available to patients aged >=60 years in India. Result(s): We enrolled 1762 patients;1342 (76.2%) were male. The mean age was 68.4 (SD, 5.8) years;795 (45%) patients were from the west zone of India. Only 12 (0.68%) patients had received the pneumococcal vaccine, and 13 (0.7%) had received the influenza vaccine. At least one dose of the COVID-19 vaccine had been taken by 1302 of 1562 patients (83.3%). On univariate logistic regression, education, marital status, geographic zone of residence, and primary tumor site were correlated with the uptake of COVID-19 vaccine. Factors associated with a greater COVID-19 vaccine uptake included education (up to Std 10 and higher vs. less than Std 10: Odds Ratio [OR], 1.46;95% confidence interval [CI], 1.07-1.99;P = 0.018, and illiterate vs. less than Std 10: OR, 0.70;95% CI, 0.50-0.99;P = 0.041), marital status (unmarried vs. married: OR, 0.27;95% CI, 0.08-1.08;P = 0.046, and widow/widower vs. married: OR, 0.67;95% CI, 0.48-0.94;P = 0.017), lung and gastrointestinal vs. head-and-neck primary tumors (lung cancer vs. head-and-neck cancer: OR, 1.60;95% CI, 1.02-2.47;P = 0.038, and gastrointestinal vs.head-and-neck cancer: OR, 2.18;95% CI, 1.37-3.42;P < 0.001), and place of residence (west zone vs. central India: OR, 0.34;95% CI, 0.13-0.75;P = 0.015). Conclusion(s): Fewer than 1 in 100 older Indian patients with cancer receive routine immunization with influenza and pneumococcal vaccines. Hearteningly, the uptake of COVID-19 vaccination in older Indian patients with cancer is over 80%, possibly due to the global recognition of its importance during the pandemic. Similar measures as those used to increase the uptake of COVID-19 vaccines during the pandemic may be beneficial to increase the uptake of routine vaccinations.Copyright © 2023 Cancer Research, Statistics, and Treatment.

ID: 218414 Queen Mary University London Postgraduate Certification in Neuromodulation- Accreditation in Neuromodulation

Introduction: There is a distinct unmet need in structured, curriculum based, unbiased education in neuromodulation. Current teaching is through sporadic industry workshops, cadaver courses and peer proctorship. The COVID pandemic has created a unique opportunity where online platforms have enabled education to be delivered remotely in both synchronous and asynchronously. The William Harvey Research Institute, Queen Mary University, London, UK have initiated University based accreditation- Post Graduate Certificate in neuromodulation (PGCert) that provides candidate a qualification in one academic year through part-time study. Method(s): The program underwent rigorous staged university approval process (figure 1). To ensure market feasibility, two short proof of concept CPD programs "Executive Education in Neuromodulation (EEPIN)" were delivered in 2021. These courses attracted 87 candidates across Australia, Singapore, India, Germany, Poland, Czech Republic, Ireland, and UK. The faculty includes key opinion leaders that will deliver the program ensuring the candidates gain academic background and specialist skills to understand safe practice of neuromodulation. The PGCert advisory board has been established to ensure strict governance in terms of content and unbiased delivery confirming ACCME guidance. In order to obtain PGCert, candidates are required to complete 4 x 15 credit modules (60 credits). The four modules include Anatomy & Neurophysiology;Patient care and Procedurals skills;Devices and available technology;Intrathecal drug delivery for cancer and non-cancer pain. The modular nature of the program is designed to provide cumulative knowledge, from basic science to clinical application in line with the best available evidence. The modules comprise nine lectures, spreading over three consecutive days, followed by a written assignment with 40 direct contact hours in each module. The webpage can be accessed at Results: The anonymous data from EEPIN reported on Likert scale 1-5: Objectives defined 30.6% - 4 and 69.4% -5;Relevance of topics 10.2%- 4 and 89.8% -5;Content of presentations 22.4%- 4 and 77.6% -5;Organization 24.5% -4 and 69.4% -5;Candidate faculty interaction 14.3% -4 and 81.6% -5. 97% of the EEPIN candidates recommended the program to others whilst 81.8% expressed their strong interest to enroll for university-based post graduate qualification if offered. Conclusion(s): This PGcert Neuromodulation is a unique, university accredited program that provides qualification in neuromodulation with access to a flexible online e-learning platform to discuss and exchange ideas, share knowledge in candidate's own time. This will support the ongoing need for formal curriculum-based education in neuromodulation. Disclosure: Kavita Poply, PHD: None, Phillippe Rigoard: None, Jan Kallewaard, MD/PhD: None, FRANK J.P.M. HUYGEN, MD PhD: ABBOTT: Speakers Bureau:, Saluda: Consulting Fee:, Boston Scientific: Consulting Fee:, Grunenthal: Speakers Bureau:, Pfizer: Speakers Bureau:, Ashish Gulve, FRCA, FFPMRCA, FFPMCAI, DPMed, FCARCSI, MD, MBBS: None, Ganesan Baranidharan, FRCA: None, Sam ELDABE, MD, FRCA, FFPMRCA: Medtronic: Consulting Fee:, Medtronic: Contracted Research:, Mainstay Medical: Consulting Fee:, Saluda Medical: Consulting Fee:, Boston Scientific: Contracted Research:, Saluda Medical: Contracted Research:, James Fitzgerald, MA,PhD: St Jude Medical: Consultant: Self, Medtronic: Consulting Fee:, UCB: Contracted Research:, Merck: Contracted Research:, Serge Nikolic, MD: None, Stana Bojanic, BSc MBBS FRCS (SN): Abbott: Contracted Research:, Habib Ellamushi: None, Paresh Doshi, MS MCh: None, Preeti Doshi, MBBS, MD, FRCA: None, Babita Ghai, MBBS, MD, DNB: None, Marc Russo, MD: Presidio Medical: Ownership Interest:, Saluda Medical: Ownership Interest:, Boston Scientific: Contracted Research: Self, Mainstay Medical: Contracted Research: Self, Medtronic: Contracted Research: Self, Nevro: Contracted Research: Self, Saluda Medical: Contracted Research: Self, Presidio Medical: Contracted Research: Self, Freedom Ne ro: Ownership Interest - Own Stocks: Self, Lungpacer: Ownership Interest - Own Stocks: Self, SPR Therapeutics: Ownership Interest - Own Stocks: Self, Lawrence Poree, MD,MPH,PHD: Medtronic: Consulting Fee: Self, Saluda Medical: Contracted Research: Family, Nalu Medical: Contracted Research: Family, Gimer Medical: Consulting Fee: Self, Nalu Medical: Consulting Fee: Self, Saluda Medical: Consulting Fee: Self, Nalu: Ownership Interest:, Saluda Inc: Ownership Interest:, Alia Ahmad: None, Alaa Abd Sayed, MD: Medtronic, Abbott, SPR and StimWave: Consulting Fee:, Salim Hayek, MD,PhD: None, CHRISTOPHER GILLIGAN, MD MBA: Persica: Consulting Fee: Self, Saluda: Consulting Fee: Self, Mainstay Medical: Contracted Research: Self, Sollis Therapeutics: Contracted Research: Self, Iliad Lifesciences, LLC: Owner: individuals with legal ownership in a company:, Vivek Mehta: NoneCopyright © 2023

Management of lung cancer in the COVID-19 pandemic: A review

Since its inception, the COVID-19 pandemic has affected health care as a whole. Cancer patients in general and those suffering from lung cancer in particular are a vulnerable group because of their many intrinsic characteristics and care needs. How SARS-CoV-2 (COVID-19) infection affects these patients regarding their risk of infection and outcome in this patient cohort is still to be determined. In this review, we tried to summarize our main concerns regarding COVID-19 in the context of cancer patients from a clinical and multidisciplinary approach. Different types of lung cancer treatments (chemotherapy, radiation therapy and immunotherapy) may also influence the risk of infection and condition the patient's risk of having a worse outcome. Lung cancer patients require frequent radiologic study follow-ups, which may be affected by COVID-19 pandemic. COVID-19 related incidental radiologic findings can appear in routinely scheduled radiology tests, which may be difficult to interpret. Also cancer treatment induced pneumonitis may have similar radiologic features similar to those in acute SARS-CoV-2 pneumonia and lead to a wrong diagnosis. The different health care needs, the requirement for continuous health care access and follow-ups, and the clinical traials in which this patient population might be enrrolled are all being affected by the current COVID-19 health crisis. The COVID-19 pandemic has put health care providers and institutions in difficult situations and obliged them to face challenging ethical scenarios. These issues, in turn, have also affected the psychological well-being of health care workers.Copyright © The Author(s) 2021.

Unmasking the Diagnosis of Acromegaly

The diagnosis of acromegaly is still a difficult task, as the disease has a slow onset and progression, and some of its symptoms may resemble those of other common conditions. Delays in diagnosis are common. Moreover, due to the continuous requirement for mask-wearing in many healthcare settings to prevent the spread of COVID-19, it is crucial to conduct a comprehensive examination of each patient without a face mask.Copyright © The Author(s). 2022.

Navigating the iodinated contrast media shortage: A review

The current COVID-19 climate has caused an unforeseen supply shortage of iodinated contrast media (ICM) worldwide, disrupting global distribution.1 In addition, the scarcity has resulted in a ripple effect in healthcare facilities such as radiology departments where ICM is required to perform contrast-enhanced examinations. ICM plays a significant part in contrast-enhanced CT, angiography and fluoroscopic procedures within the radiology department, holding a primary role in the differentiation and diagnosis of pathologies which range from pulmonary emboli to tumours.1 Its use extends beyond radiology, where ICM is heavily relied on in cardiology, urology and gastrointestinal studies, further highlighting the heavy dependence on the critical agent.2 With the global increase in the number of CT examinations requested, where approximately 60% of studies require ICM, optimal usage of ICM must be considered to meet heightened demand.3 The shortage has represented an opportunity for imaging providers to re-examine current imaging protocols and identify whether non-contrast imaging, alternative contrast agents and other imaging modalities could be viable options moving forward.1,2 Additionally, current literature has discussed volume-reduction strategies and dual-energy use in newer-generation CT scanners to conserve ICM.1,4 This review will explore currently proposed solutions that can be implemented in the radiology department to maximise ICM supply with minimal impact on patient care.

Enoxaparin Sodium Biosimilar in the Prophylactic Treatment of Veinous Thromboembolism and Thromboembolic Disease: Prophyvar Study

Objectives: Varenox is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE). Method(s): This is an observational, prospective, multicenter study, conducted between April 2021 and May 2022. The primary safety outcome was the incidence of Adverse Events (AEs) related to the study drug. A sample size of 500 patients was calculated to estimate the proportion of patients with AEs. Assuming that approximately 10% will be lost to follow-up or not evaluable, 550 patients were needed to describe the impact of Varenox use. Result(s): The study was conducted in 25 different sites in Algeria, in 4 therapeutic areas: ICU, orthopedic surgery, obstetrics and nephrology;550 patients were included and received at least one injection of Varenox. The mean age was 47 years, women in majority (62.5%). The patients were overweight or obese (53%), with a history of arterial hypertension (25%), diabetes (7.5%) and renal failure (6.4%). Reasons for hospitalization were mainly fracture (15.5%), pregnancy (8.3%), COVID-19 (7%) or cancer (7%). The majority of patients were treated at prophylactic dose of 0.4ml (80%) or 0.6ml (10%). The median duration of follow-up was 24 days. A total of 38 patients experienced at least one AE (6.9%, CI95=[4.9%;9.4%]). Related AEs were reported in 10 patients (1.8%), mainly in nephrology (N=7 arterio-venous fistula). VTE events were reported in 6 patients (1.1%, CI95=[0.2%;2%]). Conclusion(s): This study suggests that Varenox is safe in the prophylaxis of VTE. To our knowledge this is the first large study describing the use of ES in current medical practice in Algeria.Copyright © 2023

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.

Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

T-cell mediated response to emerging COVID19 strains in patients with cancer studied via deep learning

Cancer patients, particularly those receiving B cell-depleting therapy for lymphoid malignancies, are at risk of prolonged SARS-CoV-2 infection, poorer clinical outcomes, and delayed initiation or disruption of cancer-directed therapy (Lee at al., 2022, Clark et al., 2021). We first studied T-cell mediated response to the Wuhan strain of SARS-CoV-2 in a cohort of 69 patients with hematologic and solid cancers, including 18 patients who received prior B-cell depleting therapy. Patients with prolonged COVID-19 clearance, defined by a positive PCR test for longer than 30 days, had a broad but poorly converged CD8+ dominant response and a lacking CD4+ response. To conduct this analysis, we performed bulk T-cell receptor (TCR) sequencing of 121 blood samples and tracked over time TCR repertoire statistics such as clonality, convergence, breadth, and depth of COVID-19-associated TCRs during the active and convalescent periods of COVID-19 infection. These SARS-CoV-2-associated TCRs were identified leveraging immunoSEQ T-MAP database (Snyder et al., 2020), a set of TCR sequences derived from COVID-19 patients and experimentally identified as responsive to MHC Class I and II epitopes from the Wuhan SARS-CoV-2 strain using the multiplex identification of TCR antigen assay (Klinger et al., 2015). To extend our TCR repertoire analysis to other SARS-CoV-2 variants, including Omicron, we developed a deep learning (DL) method to predict TCR specificities for new SARS-CoV-2 epitopes. This DL approach also permits the identification of SARS-CoV2-responsive TCRs private to an individual. Combining this DL approach with our TCR statistics methodology, we studied the dynamics of T-cell response to COVID-19 vaccinations in a cohort of 50 patients with cancer and analyzed TCR repertoire characteristics associated with different degrees of COVID-19 severity in a cohort of 42 cancer patients who contracted the Omicron. Understanding cellular response to novel infections is critical for patient care in the context of cancer, and our novel DL-based approach can leverage existing datasets to analyze and track response to emerging viral strains.