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.

Remdesivir Reduces Mortality in Immunocompromised Patients Hospitalized for Covid-19

Background: There is limited information on effectiveness of COVID-19 therapies in immunocompromised patients, who are at higher risk of hospitalizations, complications, and mortality due to COVID-19. We examined hospital all-cause mortality for early RDV use vs. no RDV use among immunocompromised COVID-19 patients across several distinct dominant variants of concern (VOC) periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we identified adults with an immunocompromised condition (cancer, solid organ and hematopoietic stem cell transplant, hematologic malignancies, primary immunodeficiencies, asplenia, bone marrow failure/aplastic anemia, severe combined immunodeficiencies or HIV), hospitalized with a primary diagnosis of COVID-19. Patients treated with RDV in first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using 1:1 preferential withinhospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Cox Proportional Hazards Model was used to examine time to 14-and 28-day mortality. Result(s): Overall (Dec'20-Apr'22), 14,169 RDV-treated patients were matched to 5,341 unique non-RDV patients. Post-matching balance was achieved with 59% being 65+ years, 40.5% with no supplementary oxygen charges, 39% received low-flow oxygen, 19% on high-flow oxygen/non-invasive ventilation and 1.5% on invasive mechanical ventilation/ECMO at baseline. During the study period, unadjusted mortality rate was significantly lower for RDV patients at 14 days (11% [95% CI: 11%-12%] vs 15% [15%-16%];p< .0001) and 28 days (18% [17%-18%];p< .0001 vs 22% [22%-23%];p< .0001) as compared to patients that did not receive RDV. After adjusting for baseline and clinical covariates, 14-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (30% lower risk), pre-delta (41%), Delta (23%), Omicron (25%)]. Similarly, 28-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (25%), pre-delta (35%), Delta (21%), Omicron (16%)] (Fig). Conclusion(s): Timely initiation of RDV in first two days of hospital admission demonstrated significant mortality reduction in immunocompromised patients hospitalized with primary diagnosis of COVID-19. RDV demonstrated consistent benefit in an immunocompromised cohort across all variant periods of the pandemic.

TCR Alpha Beta and CD19+ Depleted Haploidentical Peripheral Stem Cell Transplantation Using Reduced Toxicity Conditioning Regimen with Pharmacokinetics Guided Busulfan, Fludarabine, Thiotepa and Thymoglobulin Offers Durable Donor Engraftment in Children with Primary Immune Deficiency Disorders

Background: Allogeneic hematopoietic cell transplantation (HCT) with ex vivo T cell receptor (TCR) alphabeta+ T cell and CD19+ B cell depletion is an effective approach for children with primary immune deficiency disorders (PIDD) as it combines advantages of high CD34+ cell dose facilitating rapid engraftment with low risk of Graft Versus Host Disease (GVHD). The ideal pre-conditioning regimen that facilitates robust donor engraftment without increasing risk of transplant related mortality has not been well defined with this approach. Method(s): We report the outcomes of 4 pediatric subjects: Chronic Granulomatous Disease (CGD) (2), Wiskott Aldrich Syndrome (WAS) (1), and RAC2 deficient Severe Combined Immunodeficiency (1) who underwent haploidentical HCT with TCRalphabeta+ T cell/CD19+ depletion at Johns Hopkins All Children's Hospital/Moffitt Cancer Center from 2020-2022 (NCT04414046). Pre-conditioning regimen consisted of distal thymoglobulin (7.5 mg/kg), fludarabine (175 mg/m2), thiotepa (10 mg/kg) and pharmacokinetic guided busulfan targeting a cumulative area under curve (cAUC) (65-75 mgxhr/L). Rituximab (200 mg/m2) was administered on day +1. Result(s): The median age at HCT was 51 months (range 10-163 months). All patients received mobilized peripheral blood stem cells from HLA- haploidentical donors (paternal=1, maternal=1 sibling=2). Median busulfan cAUC for all patients was 69 mgxhr/L (range 65-76). Median CD34 and TCR alphabeta T cell dose was 9.13x106 cells/kg (range 7.0-18.9x106) and 0.7x105 cells/kg (range 0.09-1.0x105). Median times to neutrophil and platelet engraftment were 11 days (9-12) and 11 days (range 8-15), respectively. All 4 patients are alive with median follow-up of 19.5 months (range 7-24). One patient developed late VOD without organ dysfunction that resolved with defibrotide. At last follow up, peripheral T and myeloid chimerisms exceeded 90% in all 4 patients. Average time to CD4 recovery (> 200x106/L) was 142 days. Pre-existing inflammatory bowel disease in CGD (n=1) and WAS (n=1) patients resolved immediately following transplant. There was no graft failure, and none developed Grade III-IV acute or extensive chronic GVHD. Patient with WAS developed recurrent autoimmune cytopenias requiring corticosteroids, rituximab, sirolimus and daratumumab, and ultimately resolved. Viral reactivations included EBV (n= 1), adeno (n= 1), HHV6 (n= 2), BK (n=1), norovirus (n=1), and late HSV (n=1), all responded to antivirals without disease. All patients acquired SARS-Cov-2 after transplant and recovered without sequelae. Conclusion(s): TCR alphabeta+ and CD19+ depleted haploidentical transplantation using a reduced toxicity conditioning regimen with pharmacokinetic guided busulfan, fludarabine, thiotepa and thymoglobulin is well-tolerated in young children with PIDD that results in rapid, durable engraftment with low likelihood of GVHD and graft rejection.Copyright © 2023 American Society for Transplantation and Cellular Therapy

A clinical case of combined immunodeficiency diagnosed by TREC assay

Early diagnosis and timely treatment of combined immunodeficiency (CID) is extremely important for the child's future life. At birth, children often have no specific signs of the disease, Put from the first months of life CID manifests Py severe infections that can impact on the results of further treatment. Detection of T-cell lymphopenia by determining the number of T-cell receptor excision circles (TRECs) in a dry spot after the birth of a child formed the basis for newborn screening for severe CID. KREC (kappa-deleting recombination excision circle) assay is used for detection of B-cell lymphopenia. Clinical case. We report the first case of CID (T-B+NK+) suspected by detection of TREC in Ukraine in a 2.5-month-old child. Immunodeficiency was manifested by severe complicated pneumonia at the age of 2 months, which had an atypical course and was resistant to treatment. A screening study to detect T- and B-lymphopenia using the TREC/KREC assay twice showed a zero TREC value and a KREC number of 3.12×105per 106cells, indicating severe CID. Subsequent immunological studies confirmed the deficiency of T-cell immunity. Venous thrombosis and increasing multiorgan failure led to the death of the child. Thus, newborn screening using TREC assay will allow the timely detection of severe combined immunodeficiencies with further adequate therapy and measures to prevent life-threatening infections, including SARS-CoV-2. The research carried out in accordance with the principle of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. © 2022 by the Author(s).

Advances and Challenges of the Decade: The Ever-Changing Clinical and Genetic Landscape of Immunodeficiency.

In the past 10 years, we have witnessed major advances in clinical immunology. Newborn screening for severe combined immunodeficiency has become universal in the United States and screening programs are being extended to severe combined immunodeficiency and other inborn errors of immunity globally. Early genetic testing is becoming the norm for many of our patients and allows for informed selection of targeted therapies including biologics repurposed from other specialties. During the COVID-19 pandemic, our understanding of essential immune responses expanded and the discovery of immune gene defects continued. Immunoglobulin products, the backbone of protection for antibody deficiency syndromes, came into use to minimize side effects. New polyclonal and monoclonal antibody products emerged with increasing options to manage respiratory viral agents such as SARS-CoV-2 and respiratory syncytial virus. Against these advances, we still face major challenges. Atypical is becoming typical as phenotypes of distinct genetic disease overlap whereas the clinical spectrum of the same genetic defect widens. Therefore, clinical judgment needs to be paired with repeated deep immune phenotyping and upfront genetic testing, as technologies rapidly evolve, and clinical disease often progresses with age. Managing patients with organ damage resulting from immune dysregulation poses a special major clinical challenge and management often lacks standardization, from autoimmune cytopenias, granulomatous interstitial lung disease, enteropathy, and liver disease to endocrine, rheumatologic, and neurologic complications. Clinical, translational, and basic science networks will continue to advance the field; however, cross-talk and education with practicing allergists/immunologists are essential to keep up with the ever-changing clinical and genetic landscape of inborn errors of immunity.

VALIDITY OF THE CHINESE LANGUAGE VERSION OF THE PATIENT HEALTH QUESTIONNAIRE-9 (PHQ-9) FOR DEPRESSION SCREENING: A SYSTEMATIC REVIEW

BACKGROUND: Depression is a major public health issue, yet Chinese Americans are less likely to be diagnosed and have their symptoms treated. Chinese Americans with Limited English Proficiency (LEP) have higher mental health needs than their English-proficient counterparts but have significantly lower rates of mental health service utilization. Furthermore, the increase in anti-Asian hate crimes during the COVID-19 pandemic has increased the urgency to accurately detect depression in this community. This systematic review examines the validity of the PHQ-9 for depression screening in Chinese-speaking populations. METHODS: We conducted a systematic review of English and Chinese articles in PubMed, Web of Science, Embase, and the PsycINFO databases examining studies through September 2021. Studies were included if they: evaluated the Chinese language PHQ-9, conducted a clinical interview (gold standard) to diagnose depression and depressive symptoms, and included measures of validity and efficacy of the PHQ-9. We included studies conducted in the US and abroad, regardless of the Chinese language spoken, as most relied on the same written Chinese PHQ-9. Three investigators independently reviewed titles and s for all citations to identify studies that met inclusion criteria, which advanced to full-text review. Using a standardized data extraction form, we ed: country and setting, participant characteristics, sample size, study design, years of study, gold standard utilized, and outcome measures. Two investigators independently assessed the study quality using the QUADAS-2 (which is specific for assessing potential for bias in studies of diagnostic accuracy). RESULTS: Our search identified 424 articles;44 articles received a full text review. Of those, 14 articles (N= 10,813 participants), conducted in Mainland China (N=12), Hong Kong (N=1), and the United States (N=1), met inclusion criteria and were included in the review. Studies were diverse in terms of participant age, comorbidities, and setting. Gold standards used included: MINI (N=7), SCID (N=6), and DSM-V (N=1). Overall, Cronbach's alpha ranged from 0.80-0.94 for included studies and optimal cutoff scores ranged from 6-15. Studies had an overall low risk for bias. CONCLUSIONS: While there were limited studies and variable reference standards used, the Chinese language version of the PHQ-9 appears to be a valid depression screening tool among Chinese-speaking populations in multiple countries and various clinical settings. Further research should explore the optimal cut-off score for this population.

SARS-2 related HUPRA syndrome presenting with neonatal lactic acidosis

Introduction: Mitochondria are organelles that fulfill the energy requirements for cells, which is essential for their survival and function. Mitochondria function is dependent on both mitochondrial (mtDNA) and nuclear genes (Tucker, 2010). SARS2 is a nuclear gene that encodes the mitochondria seryl-tRNA synthetase precursor. It catalyzes the attachment of serine to tRNA and in the biosynthesis of selenocysteinyl-tRNA in the mitochondria. Pathogenic variation in the gene is associated with HUPRA syndrome, which is characterized by hyperuricemia, pulmonary hypertension, renal failure, and metabolic alkalosis (Rivera, 2013). It is important to recognize this autosomal recessive condition as it presents in infancy, can lead to death, and has recurrence implications for carrier couples. Case Description: We present a term neonate male who experienced tachypnea at birth requiring respiratory support;echocardiogram concerning for pulmonary hypertension and right ventricular hypertrophy requiring ionized nitric oxide. During his hospitalization, he developed lactic acidosis (consistently 10–12 mmol/L, reaching 26 mmol/L), seizures, and his newborn screen results flagged as abnormal for severe combined immunodeficiency (SCID) due to low Tcell count. He was transferred to a tertiary medical center due to continued elevated lactate levels. During admission to the tertiary medical center, he was found to have hyperkalemia, elevated BUN/Cr, and elevated lactate levels. Additionally, pre-prandial and postprandial lactate and pyruvate levels were obtained. It was found that hyperlactatemia was persistent and not related to feedings. The patient developed a presumed pulmonary hypertensive crisis at 8 weeks of age, and in the setting of chronic intrinsic renal dysfunction and chronic lactic acidosis, the family elected to transfer him to the home hospital for compassionate extubation where he died. Notable genetics evaluation findings included urine organic acid results showing markedly and persistently elevated levels of fumaric acid and lactic acid concerning for fumarase deficiency or a mitochondrial oxidative phosphorylation disorder and plasma amino acids showing elevated alanine and proline indicative of lactic acidosis. An array CGH showed 2% areas of homozygosity, consistent with known shared parental ancestry. The results of combined mitochondrial genome and Mitochondrial Nuclear Gene Panel was ordered. The results revealed two SARS2 variants: (c.988C>T,p.R330W and c.173T>A, p.L58Q). Both variants were classified as variants of uncertain significance (VUS) based on ACMG-AMP criteria (Richards, 2015) and parental testing to determine phase is ongoing. Discussion: Pathogenic variants in SARS2 lead to dysfunction of seryltRNA synthetase and is associated with HUPRA syndrome. Our patient harbors two variants in SARS2 classified as VUSes but based on clinical presentation the phenotype is consistent with HUPRA syndrome. The condition was first described in 2011 (Belostotsky, 2011) with 6 reported patients from 3 families (Belostotsky, 2011 and Rivera, 2013). Further study into pathogenic mechanism is important as no treatment exists, and the disease leads to death of the infants affected. Although the disease is very rare, it must be considered in infants with who present with symptoms of failure to thrive, hyperuricemia, pulmonary hypertension, renal failure, and metabolic alkalosis.

Health disparities stemming from race and ethnicity differences: best practices for reporting demographics in newborn screening research

he recent and persistent COVID-19 pandemic highlights the mounting published data on health disparities in the United States, including higher mortality in minority communities due to systemic racism embedded in our society. Throughout history, “race” has been supposition as a biological variable instead of a social and political construct that has changed throughout history. Using race and ethnicity as variables in human genomic research has had negative consequences for how the research is translated into clinical practice, incorporated into public health programs, and implemented in public policy. Newborn screening (NBS) is one of few public health programs that does not target a particular population and is available to every infant born in the United States regardless of race or socioeconomic status. Each year during the process of screening 4 million newborns for over 80 disorders, state-based public health programs collect a variety of demographic and birth-related data. The potential to leverage the data collected could improve our understanding of diseases and interventions, and in time, could transform healthcare by reducing the health disparity gap. However, inaccuracies or misuse of non-biological variables such as race or ethnicity can lead to social harms and unvalidated conclusions. NBS disorders are screened using a combination of biological and physiological assessments and are conducted either in the birthing hospital or in a state public health laboratory. The laboratory measurements are performed using a blood sample collected on filter paper card. These dried blood spot (DBS) cards also list demographic and birth data that is vital to interpreting test results. Although the list of data collected varies across state programs, most programs collect sex, birth weight, gestational age, the use of antibiotics, feeding type, and/or transfusion status. Residual DBS are a valuable resource and state programs store them for use in program improvement activities and research. Over two-thirds of state programs store residual DBS for longer than one year, and at least 18 include consent for research as one of the collected data points. While NBS research studies often rely on data collected on the DBS card for reliable variables, some of the data represents demographic information provided by the parents and collected at the birthing center. It is not uncommon for healthcare professionals who collect the DBS specimen to infer the newborn’s ascriptive race and/or ethnicity. This leads to potentially inaccurate data that has been used in NBS research studies to characterize study populations and provide conclusions about rare mendelian disorders in specific racial and ethnic populations. The accurate representation of race and ethnicity is always important, especially when a condition is added to nationwide screening. In 2010, NBS for severe combined immunodeficiency (SCID), a life-threating disorder caused by the lack of T-cells, was recommended for nationwide screening. Prior to screening, diagnosed patients that were followed long-term were predominately white (81%). However, a recent publication of screening results from 3.25 million California infants reported that SCID did not occur more frequently in any ethnic group, and found no predominant founder mutation. SCID frequently occurred because of homozygous autosomal recessive inheritance, and 80% of cases have no family history. Accurate representation of race and ethnicity could be used to assess health outcomes and disparities across all racial groups and other biological variables such as genetic ancestry should be considered to help advance the understanding of etiology of SCID.This presentation will exam how race and ethnicity is collected from NBS programs in the United States and how race is used in published NBS literature. Additionally, we will explore the lack of standardized language used to collect information on race and ethnicity in NBS and the incorrect assumption that race and ethnic information is based on parent report. We wil discuss the impact of these practices on NBS research, propose best practices for reporting race and/or ethnicity to ensure accurate evaluation of health outcomes and disparities, and recommend that NBS researchers use other biological variables such as genetic ancestry in research to assess true disease risk

Highlights from this issue

Correspondence to Dr Nick Brown, Department of Women’s and Children’s Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden;nickjwbrown@gmail.com What the brochure says The WHO top ten list of threats to global health feature many directly relevant to children: climate change, pollution;vaccine hesitancy;dengue;COVID-19;influenza;antimicrobial resistance – all ‘deserving members’ of this unenviable top table, though the non-inclusion of female literacy baffles me. Melody Redman’s systematic review of the use of low level laser prophylaxis to the oral mucosa suggests doors might be opening: pain free periods after chemotherapy, enjoyment of food, independence of parenteral nutrition and nasogastric tubes. Sam Oddie discusses the downsides to the proposed delay to routine BCG vaccination in high risk babies while waiting for the result of the newly introduced screening programme for severe combined immunodeficiency (SCID), the principles being on the one hand that vaccination will leave a small number of babies exposed to disseminated BCG and on the other that the remainder (many times more) will be unprotected during an early life window of vulnerability particularly if surrounded by household contacts.

SOCS1 Haploinsufficiency Presenting As Incidental Refractory Thrombocytopenia in a Pediatric Patient with Inflammatory Symptoms and History of Sars Cov-2 Infection

BACKGROUND: Immune thrombocytopenia purpura (ITP) has a complex pathogenesis and may be a primary diagnosis or secondary to an underlying condition 1. Evaluation for underlying diagnoses in patients presenting with atypical features of classic ITP is key, as this can impact treatment decisions, therapy response, and prognosis. Genetic variants that predispose patients to ITP are especially important to investigate as patients may be at risk for additional autoimmune phenomenon or malignancy. The SARS CoV-2 pandemic has added further complexity as reports suggest the infection can lead to autoimmunity in those with genetic predispositions 2,3. Loss of the suppressor of cytokine signaling 1 (SOCS1) function has been described to manifest with autoinflammatory syndrome, with or without immunodeficiency 4,5. Reports of autoimmunity developing in patients with SOCS1 haploinsufficiency after SARS CoV-2 infection are documented, including multi-system inflammatory syndrome (MIS-C) 2. A proposed mechanism of this virus-triggered autoimmunity includes a transient innate and adaptive immunodeficiency 3. This raises the question whether patients harboring genetic variants with risk of autoimmunity are placed at an even higher risk for ITP in the wake of SARS-CoV2 infection. CASE PRESENTATION: We present a 6-year-old female with isolated thrombocytopenia of 4,000/uL identified during evaluation for severe arthralgias unresponsive to corticosteroid treatment (maximum dose 1mg/kg/day) over a 6-month period. Laboratory results at presentation were consistent with ITP, including presence of platelet autoantibodies. Evaluation revealed hypocellularity for age (~50%) on bone marrow evaluation as well as elevated IgE (2080 kU/L), with IgA, IgM, and IgG levels within reference range. She had a remote history of SARS CoV-2-like illness and SARS CoV-2 antibodies were found present in serologic assay, without a history of vaccination. Genetic testing, including chromosomal microarray from peripheral blood and marrow, was included in the diagnostic workup given concern for a history of developmental delays with macrocephaly and necessity to rule-out malignancy with the patient noted to have a 5 mega-base deletion at 16p13.2p13.11, which includes the SOCS1 gene. Comprehensive next generation sequencing for additional immune dysregulation/primary immunodeficiency associated variants was unremarkable. Functional studies of surface expression of interferon-inducible genes (CD169 (SIGLEC-1)) and STAT1 phosphorylation via analysis of CD14+ monocytes revealed excess interferon signaling previously described in patients with SOCS1 haploinsufficiency (Figure 1). Measurements of B-cell-activating factor were also found to be extremely elevated at 6432 pg/mL. The patient's ITP course was complicated by hematuria, melena and refractory platelet response to first line therapy consisting of intravenous immunoglobulin 1 g/kg x2 doses and 2 mg/kg/day prednisolone. She required escalation to high dose methylprednisolone (30mg/kg), rituximab 375 mg/m 2/weekly x4 doses, and concurrent romiplostim (2 doses) for control of thrombocytopenia and bleeding manifestations. Her rheumatologic symptoms subsided with initiation of corticosteroids, and she has subsequently completed a prolonged corticosteroid taper. She currently has a normal platelet count with non-steroidal anti-inflammatory therapy utilized for arthralgia management with plan to transition to JAK inhibition for maintenance therapy. CONCLUSION: This case highlights the potential impact of investigating for susceptibility genes for ITP with consideration for broader testing including targeted next generation sequencing panels or microarray analysis in patients with atypical ITP presentations or response to therapy, as knowledge of this patient's underlying genetics led to earlier treatment and use of alternative agents. Additionally, the case adds the novel finding of bone marrow hypocellularity to the clinical phenotype of SOCS1 haploinsufficiency, as this has not yet been reported and contributes to the literature on the relationship of autoimmunity and SARS CoV-2 infections in patients with predisposing genetic variants. [Formula presented] Disclosures: Walkovich: Horizon Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pharming: Honoraria, Membership on an entity's Board of Directors or advisory committees;Swedish Orphan Biovitrum AB (Sobi): Consultancy, Honoraria;X4 Pharmaceuticals: Other: Local PI for clinical trial involving mavorixafor and patients with neutropenia.

COVID-19 pandemic and immunoglobulin shortages in Brazil

Background: Immunoglobulin replacement has been revolutionized the treatment of inborn errors of immunity (IEI), ensuring greater survival and quality of life for these patients. Most IEI patients need to receive continuous and regular immunoglobulin replacement. In Brazil, unfortunately, there is no production of this biological or policies for plasma reuse and its importation becomes necessary. Immunoglobulin is distributed monthly by the Brazilian Public Health System (SUS), free of charge. Apart from the difficulty in importing, we had to face the worldwide decrease in blood donations related to COVID-19 pandemic. The aim of this study was to report the rate of lack of immunoglobulins and complications related to this event. Method: This is a cross-sectional, retrospective study, based on the analysis of patient's medical charts at an IEI reference center in Brazil, from January to December 2020. Results: During this period, 124 patients received intravenous immunoglobulin (IVIG) replacement, 62 patients are female (50%), 70 adults (18 to 84 years, median age: 38y) and 54 children (0 to 17 years, median 11y). The most prevalent diagnostic were Common Variable Immunodeficiency-CVID (28.2%), Hypogammaglobulinemia (19.3%), Specific Antibody Deficiency-SAD (11.2%), Ataxia-Telangiectasia (8.8%) and other diagnostics (32,5%: SCIDS, leaky SCID, XLP2, XHIGM, VEO-IBD). Indeed, 70 patients (56.4%) were affected by the lack of distribution of IVIG (56.4%) related to COVID-19 pandemic, remaining without IVIG from one to 12 months, 2.9 months on average. Of these, 48 patients (68.5%) had at least one infection (total 125), all of whom needed to use antibiotics for the treatment of infections and 12 patients required hospitalization. Conclusion: In 2020, 70 (56.4%) patients were affected by the lack of distribution of IVIG. It was possible to identify shortage of immunoglobulin replacement in Brazil due to COVID-19 pandemic led to more infections and increase of antibiotics use.

Case Report: Convalescent Plasma Achieves SARS-CoV-2 Viral Clearance in a Patient With Persistently High Viral Replication Over 8 Weeks Due to Severe Combined Immunodeficiency (SCID) and Graft Failure.

We describe the unique disease course and cure of SARS-CoV-2 infection in a patient with SCID and graft failure. In absence of a humoral immune response, viral clearance was only achieved after transfusion of convalescent plasma. This observation underscores the necessity of the humoral immune response for SARS-CoV-2 clearance.

SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency.

X-linked severe combined immunodeficiency (X-SCID) is a disorder of adaptive immunity caused by mutations in the IL-2 receptor common gamma chain gene resulting in deficiencies of T and natural killer cells, coupled with severe dysfunction in B cells. X-SCID is lethal without allogeneic stem cell transplant or gene therapy due to opportunistic infections. An infant with X-SCID became infected with SARS-CoV-2 while awaiting transplant. The patient developed severe hepatitis without the respiratory symptoms typical of COVID-19. He was treated with convalescent plasma, and thereafter was confirmed to have SARS-CoV-2 specific antibodies, as detected with a microfluidic antigen array. After resolution of the hepatitis, he received a haploidentical CD34 selected stem cell transplant, without conditioning, from his father who had recovered from COVID-19. SARS CoV-2 was detected via RT-PCR on nasopharyngeal swabs until 61 days post transplantation. He successfully engrafted donor T and NK cells, and continues to do well clinically.