IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.

Successful matched unrelated donor hematopoietic stem cell transplantation for infantile Wolman disease

Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Dupilumab as a steroid-sparing treatment option in pediatric severe asthma and chronic rhinosinusitis with nasal polyps

Case report Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe asthma in adults. Both diseases share key pathophysiological mechanisms that can involve type-2 inflammatory pathways. However, this is an uncommon presentation in pediatric patients. Dupilumab, a fully human monoclonal antibody against IL-4Ralpha, inhibits IL-4/ IL-13 signaling, which are key drivers of type-2 inflammation and interfere with both eosinophilic and allergic pathways. It is approved for patients >= 12-year- old with moderate to severe uncontrolled asthma, but its approval in CRSwNP is limited to adults. We report a case of a 12-year- old boy with severe uncontrolled asthma and highly symptomatic CRSwNP referred to our center in May 2021. He was sensitized to house dust mite and pollens, and a specific immunotherapy had been tried previously. He was treated with high dose inhaled corticosteroid, long-acting beta agonist, long-acting muscarinic antagonist, montelukast and daily intra-nasal corticosteroids. Furthermore, a bilateral endoscopic sinus surgery with polypectomy was performed in April 2021. Despite adherence to medication and surgical treatment, both diseases were uncontrolled with frequent exacerbations requiring unscheduled visits and multiple systemic corticosteroid courses. This led to failure to thrive and several missed school days. Oral corticosteroid (OCS) tapering was unachieved due to symptoms rebound and so maintenance therapy with prednisolone 10mg daily was attempted, with only a slight improvement. High levels of eosinophils (1010 cells/muL), FeNO (122 ppb) and IgE (2255 kU/L) were present. Treatment with subcutaneous dupilumab was started in July 2021. A clinical and analytical improvement was evident at the 3-month evaluation (Table 1). He was able to stop prednisolone, and no clinically relevant exacerbations occurred. He also was fully vaccinated and had an asymptomatic COVID-19 infection in December 2021. Patients with CRSwNP and comorbid asthma have a higher disease burden than patients with each disease alone. In this adolescent, dupilumab was effective as an add-on treatment, for both severe asthma and CRSwNP. It led to disease control, OCS withdrawal, reduced eosinophilic inflammation, improved lung function, smell recovery and absence of exacerbations during follow-up. Dupilumab, targeting the type 2 inflammatory process, may allow a better management of pediatric patients >=12 years old with severe CRSwNP and comorbid asthma. (Table Presented).

Novel heterozygous PLCG2 variant presenting with very early-onset perianal abscess

Case report Background: Mutations in the PLCG2 gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID) or auto-inflammation with PLCG2-associated antibody deficiency and immune dysregulation (APLAID). PLAID is characterized by urticarial eruptions triggered by evaporative cooling along with cutaneous granulomas. APLAID may present with early-onset skin inflammation and non-infectious granulomas, uveitis, and colitis. Method(s): Case report and literature review. We performed in silico analysis for variants of uncertain significance (VUS). Result(s): A 29-day-old boy presented to emergency department for failure to thrive. He was found to be SARS-CoV2 positive, had an E. coli UTI in the setting of bilateral perinephric masses which subsequently resolved. He also had a perianal soft tissue abscess measuring 4cm in diameter. Mom reported a similar infection when she was age 2. She also reported intermittent diffuse urticaria triggered following perspiration evaporation.Abscess wall histology showed diffuse neutrophil and lymphocytic infiltration, with cultures growing polymicrobial enteric flora. His serum immunoglobulins G, A, M, and E were within reference range. Naive and memory CD4, CD8, CD19 lymphocyte subsets (including NK cells) were also within age-appropriate reference range. He had a normal neutrophil oxidative burst measured using dihydrorhodamine (DHR) flow cytometry following PMA stimulation, which ruled out a diagnosis of chronic granulomatous disease. On evaporative cooling, the patient had a 2mm wheal with surrounding erythema which resolved rapidly with warming. A targeted primary immunodeficiency panel showed a heterozygous VUS in PLCG2, c.688C > G (p.Leu230Val). The variant was absent from major databases and had a calculated CADD score of 17.77. He had symptomatic resolution after completing 3 weeks of ceftriaxone and metronidazole antimicrobials. Given the concern for PLCG2-associated very early-onset inflammatory bowel disease (VEO-IBD), a fecal calprotectin was obtained at 3 months and found to be elevated (157 mcg/g [ < = 49 mcg/g]). However, he had no symptomatic or macroscopic evidence for VEO-IBD. Conclusion(s): Presence of very early onset abscesses has not been previously described in patients with heterozygous PLCG2 deficiency. This case adds to the expanding variable phenotype of PLCG-2-associated immune dysregulation.

Older Adults, the "Social Admission," and Nonspecific Complaints in the Emergency Department: Protocol for a Scoping Review.

BACKGROUND: Older adults have a higher visit rate and poorer health outcomes in the emergency department (ED) compared to their younger counterparts. Older adults are more likely to require additional resources and hospital admission. The nonspecific, atypical, and complex nature of disease presentation in older adults challenges current ED triage systems. Acute illness in older adults is often missed or commonly disguised in the ED as a social or functional issue. If diagnostic clarity is lacking or safe discharge from the ED is not feasible, then older adults may be labelled a "social admission" (or another synonymous term), often leading to negative health consequences. OBJECTIVE: This scoping review aims to describe and synthesize the available evidence on patient characteristics, adverse events, and health outcomes for older adults labelled as "social admission" (and other synonymously used terms), as well as those with nonacute or nonspecific complaints in the ED or hospital setting. METHODS: A literature search of MEDLINE, Embase, Scopus, PsycINFO, and CINAHL was completed. Relevant reference lists were screened. Data have been managed using EndNote software and the Covidence web application. Original data have been included if patients are aged ≥65 years and are considered a "social admission" (or other synonymously used term) or if they present to the ED with a nonacute or nonspecific complaint. Two review team members have reviewed titles and abstracts and will review full-text articles. Disagreements are resolved by consensus or in discussion with a third reviewer. This review does not require research ethics approval. RESULTS: As of January 2023, we have completed the title and abstract screening and have started the full-text screening. Some remaining full-text articles are being retrieved and/or translated. We are extracting data from included studies. Data will be presented in a narrative and descriptive manner, summarizing key concepts, patient characteristics, and health outcomes of patients labelled as a "social admission" (and other synonymously used terms) and of those with nonacute and nonspecific complaints. We expect the first results for publication in Spring 2023. CONCLUSIONS: Acute illness in the older adult is not always easily identified. We hope to better understand patient characteristics, adverse events, and health outcomes of older adults labelled as a "social admission," as well as those with nonacute or nonspecific complaints. We aim to identify priorities for future research and identify knowledge gaps that may inform health care providers caring for these vulnerable patients. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38246.

How Much Do Paediatricians Know About Poverty within the Paediatric Population?

Aims Poverty is an ever increasing problem with 4.2 million children living in poverty in the UK in 2019, an increase of 600,000 from 2011(1). This has been particularly exacerbated by the COVID pandemic with an estimated 200,000 more children living in poverty in the UK since the pandemic(1). Poverty can affect multiple aspects of children's health and wellbeing, putting additional strain on already stretched NHS recourses. We wanted to assess paediatricians' knowledge about poverty, particularly around prevalence, risk factors, the effect on children's health and wellbeing and how to help families if there are concerns of poverty. From this we hoped to highlight areas where more education and support is required. Methods We designed an online survey with 11 questions including a mixture of multiple choice and free text answers. The questionnaire was distributed to all doctors working in paediatrics at a tertiary paediatric hospital, over a 4 week period. Results There were 29 respondents in total, with grades ranging from FY1 to consultant. Nearly two-thirds of respondents underestimated the prevalence of poverty in the UK and 38% underestimated the prevalence by half or more. Over 80% of respondents underestimated the percentage of children living in poverty locally. All respondents recognised parental disability and unemployment as risk factors for poverty and 90% recognised child disability or serious illness as a risk factor. Only one person suggested parental drug and alcohol use as a risk factor. The respondents were able to list a wide range of health implications of poverty, the most common answers being failure to thrive/poor nutrition, obesity, tooth decay and poor mental health. Two-thirds of respondents admitted not feeling at all comfortable about asking parents about poverty and 40% felt that they never screen for poverty when assessing patients. To assess for poverty 34% would ask about employment, 24% about housing and 41% about benefits and additional supports. All respondents would like further education and support around poverty. Conclusion Overall there was good understanding of the health implications associated with poverty and the risk factors for poverty, but an under-appreciation of the scale of the problem. The majority of doctors do not feel comfortable asking patients and families about poverty, and do not regularly ask about poverty when assessing patients. In order to identify children living in poverty and be able to signpost families to resources that could be beneficial to them, we need to equip paediatricians with the knowledge and skills to assess for poverty and what resources are available for families in the local area. To aid this we have produced a poster to be used to in the local Emergency Department and outpatients to remind doctors about poverty, advice on how to approach the topic and resources available in the hospital and in the local area that be used to sign post families.

Conversion of Stuporous Catatonia to Excited Catatonia from Lorazepam Challenge

Background: Catatonia, a motor dysregulation syndrome with behavioral components, has undergone many conceptual changes since its inception as a syndrome by Kahlbaum in 1874. Prevalence of catatonia in consultation-liaison services is approximately 5.5 percent in patients aged 65 and older.1 Stuporous catatonia is most common, but catatonia may present in excited or malignant subtypes. Together, the subtypes have over 40 documented signs and symptoms, making catatonia difficult to diagnose and appropriately treat.2 Catatonia involves hyperactivation of the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex. GABA, NMDA, and dopamine have been implicated. GABA-A agonism by benzodiazepines improve catatonia by normalizing OFC activity.3 Case: A 66-year-old male with schizophrenia was admitted to a medical unit for failure to thrive after not eating for three days. He had not taken his medications for 2 weeks including chlorpromazine, quetiapine, oxcarbazepine, and clonazepam. Upon psychiatric consult, the patient exhibited staring, grimacing, echopraxia, and negativism. He was diagnosed with stuporous catatonia. 30 minutes after lorazepam challenge (2 milligram intravenous lorazepam), the patient was moving, conversing, and eating. After second dose of lorazepam, the patient became difficult to redirect, displaying stereotypy, verbigeration, and hitting. Additional doses of lorazepam were unsuccessful in breaking excited catatonia. History revealed previous catatonic episodes, including nine months prior when the patient was admitted to a gero-psychiatric unit. He initially presented in stuporous state, normalized with lorazepam, then transitioned to excited state. He received 16 milligrams of lorazepam in 24 hours without successful termination of excited catatonia. Lorazepam in combination with carbamazepine, clozapine, or valproic acid was unsuccessful. Catatonia was successfully treated with 10 sessions of electroconvulsive therapy (ECT) with lorazepam, clozapine, and valproic acid. Maintenance ECT was not continued because of the COVID pandemic, and the patient was admitted to a state facility after regression. Discussion: Catatonia is often encountered on consultation-liaison services in general hospital settings. We observed conversion of stuporous catatonia to excited catatonia after administration of lorazepam. This treatment-resistant catatonia ultimately required ECT. No reported cases of stuporous catatonia transitioning to excited catatonia were found on thorough literature review. Recognition of this conversion may be difficult and may require development of a catatonia scale that clearly identifies the presenting subtype. This is a challenge;clinical signs are not mutually exclusive among subtypes. This patient’s clinical course may provide insight into the identification of treatment-resistant catatonia, and accurate identification is necessary to allow for timely escalation of treatment. References: 1. Solmi M, et al. Prevalence of catatonia and its moderators in clinical samples: Results from a meta-analysis and meta-regression analysis. Schizophrenia Bulletin. 2017;44(5):1133–50. 2. Fink M, Taylor MA. The catatonia syndrome. Archives of General Psychiatry. 009;66(11):1173. 3. Ellul P, Choucha W. Neurobiological approach of Catatonia and Treatment Perspectives. Frontiers in Psychiatry. 2015;6.

“Dying of failure to thrive”: Caregiver Perspectives on the Impact of COVID-19 Isolation on Residents' Cognitive and Functional Status

Background: The COVID-19 pandemic has profoundly affected skilled nursing facilities (SNFs). Our objective was to understand SNF staff perspectives on the unintended effects of isolation protocols and suggestions for future outbreaks. Methods: Qualitative analysis of semi-structured interviews from caregivers (n=17) from seven SNFs. Interviews focused on the impact of isolation on caregiving, SNF residents' cognitive and physical health, and best practices. Virtual interviews were recorded and transcribed. Qualitative framework analysis using a modified care preparedness model was used to identify themes related to the impact of COVID-19 isolation. Results: Caregivers observed withdrawal, irritability, depression, and lack of motivation among residents. Staff noted increased confusion in cognitively impaired residents and observed that cognitively intact residents displayed more symptoms of depression. Most participants related residents' emotional changes to lack of family visitation and loneliness. SNFs connected residents with families using technology and modified visits. Staff also developed creative programming to engage residents while maintaining physical distancing, such as a mobile ice cream cart. Challenges included less hands-on caregiving due to fear of COVID-19 transmission, staff turnover, personal protective equipment (PPE) shortages, and COVID-19 outbreaks. Many participants also noted inadequate administrative support and hoped for more aid and flexibility. Staff reported that increasing family communication and physical and psychological therapy interventions worked well for residents. Staff who perceived early initiation of infection control measures (e.g., closing admittance, frequent testing, maintaining PPE supplies) and/or had highly involved administrators (e.g., open door policy, visible on the floor) felt better equipped to care for residents. Most also noted strong coworker camaraderie. Staff recommendations for quantifying the effects of isolation included tracking physical and cognitive measures longitudinally to identify changes in resident status. For future epidemics, staff emphasized the need for communication and preparation with ample supplies and staff. Conclusions: This analysis includes suggestions for preparation, communication, enforcement of infection control policies for future outbreaks.

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.

The dichotomy of social isolation in a global pandemic: when the power to protect actually harms

What was thought to be a short-term disease process, isolated to East Asia, has continued, with forecasts of subsequent "waves" mimicking three separate waves of the 1918 Spanish flu.106 Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, has recently warned Congress that COVID-19 cases could ultimately reach 100,000 per day.107 Further, it could be a year or more before an effective vaccine has been created, tested, proven safe, and ready for administration to the world's population.108 Or it could be never, as is the case with the Human Immunodeficiency virus, Zika virus, Hepatitis C Virus, tuberculosis, malaria, West Nile, and others.109 Developing natural immunity through exposure to an active disease is the best type of immunity because it can sometimes provide life-long immunity.110 However, according to the Chief of the World Health Organization ("WHO"), Tedros Ghebreyesus, allowing a dangerous virus, like COVID-19, which is not fully understood to progress unchecked, is simply unethical.111 Therefore, herd immunity is not a feasible option to combat COVID-19.

Fatal SARS-CoV-2 and Mycobacterium tuberculosis coinfection in an infant: insights from Botswana.

We report a fatal case of SARS-CoV-2 and Mycobacterium tuberculosis coinfection in an infant, Botswana's first paediatric COVID-19-associated fatality. The patient, a 3-month-old HIV-unexposed boy, presented with fever and respiratory distress in the setting of failure to thrive. Both the patient and his mother tested positive for rifampin-sensitive M. tuberculosis (Xpert MTB/Rif) and SARS-CoV-2 (real time-PCR). Initially stable on supplemental oxygen and antitubercular therapy, the patient experienced precipitous clinical decline 5 days after presentation and subsequently died. Autopsy identified evidence of disseminated tuberculosis (TB) as well as histopathological findings similar to those described in recent reports of SARS-CoV-2 infections, including diffuse microthrombosis. TB remains a serious public health threat in hyperendemic regions like sub-Saharan Africa, and is often diagnosed late in infants. In addition to raising the question of additive/synergistic pathophysiology and/or immune reconstitution, this case of coinfection also highlights the importance of leveraging the COVID-19 pandemic response to strengthen efforts for TB prevention, screening and detection.