PEDIATRIC ASTHMA AND COVID-19

PEDIATRIC ASTHMA AND COVID-19

Pediatric Asthma And Covid-19 – Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory.

I. DEFINITION Of ASTHMA

Asthma is the most prevalent chronic respiratory disease worldwide, affected people all ethnic groups throughout all ages. Asthma also the most common chronic disease in children. Asthma can’t go away, but it can be reduced to become more severe. But its still become significant public health problem. Furthermore, asthma disproportionately affects minorities and socioeconomically disadvantages children.2

II. EPIDEMIOLOGICAL AND PREVALENCE

From epidemiological and experimental studies shows that there is relationship between environmental factors and allergic r4espiratory disease such as rhinitis and asthma.3 Air pollution could be the reason of each asthma cases in the Asia Pacific especially in urban cities with rapid developing economics, increasing infrastructure, numbers of vehicles, and reduced green spaces. Fossil fuel and transportation are the main sources of air pollution (e.g., sulfur oxide and nitrous) released into the atmosphere leading to health problems. A global study that 9–23 million and 5–10 million annual asthma emergency room visits globally in 2015 could be attributable to O3 and particulate matter (PM) with a diameter of 2.5 μm or less (PM2.5), respectively, representing 8%–20% and 4%–9% of the annual number of global visits, respectively.3

The top 3 countries for both asthma incidence and prevalence in Asia were India, China, and Indonesia, driven largely by population size nearly half (48%) of estimated O3-attributable and over half (56%) of PM2.5-attributable asthma emergency room visits were estimated in Southeast Asia (includes India), and western Pacific regions (includes China). Of all countries globally, India and China had the most estimated asthma emergency room visits attributable to total air pollution concentrations, respectively contributing 23% and 10% of global asthma emergency room visits estimated to be associated with O3, 30% and 12% for PM2.5, and 15% and 17% for nitrogen dioxide (NO2). In this global study,16 million new pediatric asthma cases could occur globally each year due to anthropogenic PM2.5 concentrations, translating to 33% of global pediatric asthma incidence. The percentage of national pediatric asthma incidence that may be attributable to anthropogenic PM2.5 was estimated to be 57% in India, 51% in China, and over 70% in Bangladesh.3

Asthma affects 1 in 12 US children aged 0 through 17 years. After decades of increases, the prevalence of asthma in this group plateaued between 2010 and 2012, decreased in 2013 from 9.3% in 2012 to 8.3%, and remained stable through 2016. In contrast, pediatric asthma prevalence in black children increased between 2001 and 2009, leveling off by 2013. In 2016, asthma prevalence in black children rose sharply to 15.7% (a 2.3% increase from 2014 and 2015), twice that of white children. This rate surpassed that of Puerto Rican children, who previously had the highest prevalence of asthma of all US children. The prevalence of asthma in children in poverty did not decrease between 2001 and 2013 and remained high in 2016 (10.5%).2

pediatric asthma and covid
Picture 1. Asthma Prevalence in Indonesia in all ages, 2013-20184

Percentages asthma more higher  in the city than villagers

Asthma has become an issue of international development as its economic and social cost have been recognized. Asthma is one of the chronic respiratory diseases (CRDs), CRD’s ) including asthma cause 15% of world deaths. Strangely we still didn’t understand exactly what can cause number of asthma increasing each year.

III. RISK FACTORS ASTHMA IN CHILDHOOD

  1. Microbial Exposure

Hygiene and environment have been suggested to become cause problem increasing the risk of asthma. Accordingly, children raised in modern environment with a scanty natural microbial burden may be prone to develop allergic diseases in view of an under stimulation of the immune system. Indeed, recent evidences showed that exposure to some microbes can protect from atopy, whereas others seem to promote allergic diseases. The timing of exposure to as well as the properties of the infectious agent, in addition to the genetic susceptibility of the host, may influence the future development of asthma.5

Data from the Copenhagen birth cohort first showed that infants carrying 3 major pathogenic bacteria in their nasopharynx (ie, Streptococcus pneumoniae, Moraxella catharralis, and Haemophilus influenzae) were more likely to develop asthma by the age of 6 years than those not carrying these microbes.6

2. Atopy

Word atopy originally from the Greek “atopos” meaning out of place.(William C. Shiel Jr., MD, FACP, FACR, Medical Definition of Atopy. Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens. ATOPY DEFINITION, American Academy of Allergy Asthma & Immunology). Data from epidemiological studies showed the strong link between asthma and atopy. Indeed, the family history of atopy is considered one of the most relevant risk factors for developing asthma.5Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma, atopic dermatitis (eczema) .

From a study showed that children who were sensitized to 1 or more aeroallergens by age 1 year had the highest rate of asthma at year 13. Children who were not sensitized at year 1 but sensitized to 1 or more aeroallergens by age 5 years had a 40% rate of asthma at age 13 years.7

3. Environmental Exposure

The increasing case of asthma in metropolitan areas was possibly because of their air pollution. An evidence from a study showed evidence that increased childhood exposure to PM2,5 and black carbon was associated with increased risk of asthma at age 12 years.5 According to the WHO, nearly one million of the 3.7 million people who died from ambient air pollution in 2021 lived in South-East Asia. Several areas in Indonesia such as Sumatra and Borneo island resulted in spikes of increased pollution and health hazard by produced smoke haze.3 Several studies have linked the smoke and haze produced by the fires to chronic respiratory problems.

Living in an environment where the number of smokers are high mainly can cause lung damage eventually when it happens near of children area or even to a pregnancy. Several negative effects of nicotine exposure on structural and functional development of the fetal lung were established, such as alteration of the alveolar phase, damage of the epithelial cells of type I, inhibition of fibroblast proliferation, reduction of the small airways caliber, increase of the muscular tone, and reduction of lung compliance. Exposure during pregnancy may be responsible for permanent modifications of the respiratory tract that can persist into adulthood and might culminate in chronic obstructive pulmonary disease.7

IV. COVID-19 IN CHILDREN WITH ASTHMA

In fact, there is still no reported cases of asthma in pediatric can be the risk factor of covid-19. Children are less commonly symptomatic with coronavirus disease-2019 (COVID-19) than adults. Those who are symptomatic less commonly require hospitalization. Among 96% of cases where age was known, only 8,1% was among children less than 18 years of age. A report of 12.055 COVID-19 patients in Italy also supports a lower risk in children, although noting that COVID-19 can affect children of any age, including infants.8

Multiple international organizations including the CDC list asthma as a prognostic factor for COVID-19 outcomes such as morbidity and mortality. There is also a theoretical risk that COVID-19 could trigger viral-induced asthma exacerbations but still no data to support.   

The clinical course of COVID-19 in children is usually milder than in adults. A study stated that 23% of children with severe form of the disease have an underlying condition.9

  • PEDIATRIC ASTHMA AND COVID-19 DIAGNOSIS

Diagnosis of pediatric asthma and covid -19 during COVID-19 Pandemic may be complicated by a similarity in symptoms between COVID-19 (dry cough, shortness of breath) and worsening asthma. As a result, even if cough history is consistent with asthma, screening protocols for COVID-19 should be applied to all children who have worsening cough or shortness of breath, and appropriate personal protective equipment worn.8

lung function test such as spirometry is specific test for diagnosing a asthma, but in terms of COVID-19 pandemic The North American guidance on passed resumption of allergy care during COVID-19 notes that for Phase 2 rollout (community infection risk declining/stable) “spirometry is still contraindicated in most scenarios because of the aerosolization risk, except in highly individualized situations in which it would be essential for immediate treatment decision that could not otherwise be made without such information and where it can be performed with appropriate precautions and room/equipment disinfection.8

  • What is parents have to know if their kids develop an asthma during this Corona Virus pandemic?

Differentiating COVID-19 from worsening asthma, or an asthma exacerbation, is challenging. As a result, pediatricians and families have an essential role in ensuring that children with asthma maintain good asthma control during this time.10

Multiple international guidelines support children with asthma remaining on their maintenance asthma medications, such as inhaled corticosteroids or antileukotrienes, during COVID-19 if they are well controlled. A statement from the European Academy of Allergy Asthma and Clinical Immunology (EAACI) notes that “since asthma itself may be a risk factor for the severity of COVID‐19 disease and since the use of ICS does not pose an increased risk for pulmonary or systemic infections in children with asthma, their regular use is unlikely to increase the risk of acquiring the infection or increasing the severity of the present infection.8

Children and adolescents with asthma should remain on their current asthma medications and still practice social distancing and make sure to avoid aeroallergen also exposure to second-hand cigarette smoking10, because it can increase the expression of the ACE2 receptors in the lower respiratory tract, which is the coronavirus receptor. Which ACE2 as the receptor for Sars-CoV-2 means it will increase susceptibility to contract the COVID-19 infection and potentially to develop a more severe form.8

pediatric asthma and covid

REFERRENCES

  1. GINA committees. POCKET GUIDE FOR ASTHMA MANAGEMENT AND PREVENTION for adults and children older than 5 years.2019. Access : https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf
  2. Shilpa J. Patel, MD,MPH, Stephen J. Teach, MD, MPH. Asthma. Pediatrics in Review, An Official Journal of the American Academy of Pediatrics. Vol 40 No II November 2019. Division of Emergency Medicine, Children’s National Medical Center, Washington, DC. Access : http://pedsinreview.aappublications.org/
  3. Ruby Pawankar, Jiu-Yao Wang, I-Jen Wang, Francis Thien. White Paper 2020 on Climate Change, Air Pollution, and Biodiversity in Asia-Pacific and Impact on Allergic Disease. Asia Pacific Association of Allergy, Asthma and Clinical Immunology. 2020. Jan;10(1):e11. Access :  https://doi.org/10.5415/apallergy.2020.10.e11
  4. Kementerian Kesehatan RI. Hasil Utama RISKESDAS 2018. Penyakit Tidak Menular, Prevalensi Asma. Access : https://kesmas.kemkes.go.id/assets/upload/dir_519d41d8cd98f00/files/Hasil-riskesdas-2018_1274.pdf
  5. Giuliana Ferrante and Stefania La Grutta. The Burden of Pediatric Asthma. Frontiers in Pediatric. June 2018. Volume 6. Article 186. Access : Frontiers | The Burden of Pediatric Asthma | Pediatrics (frontiersin.org)  
  6. Fernando D. Martinez, MD. Childhood Asthma Inception and Progression Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization. Elsevier Ltd. Volume 39, Issue 2. 2019. P 141-150. Access : Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization – ScienceDirect
  7. Frederick J. Rubner, MD, Daniel J. Jackson, MD, Michael D. Evans, MS. Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence. 2017. The Journal of Allergy and Clinical Immunology. Asthma and Lower Airway Disease. Volume 139, issue 2, P501-507. Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence – Journal of Allergy and Clinical Immunology (jacionline.org)
  8. Elissa M.Abrams MD, FRCPC. Ian Sinha MBBS, FRCPCH, PhD. Pediatric Asthma and COVID-19: The known, the unknown, and the controversial. Wiley Periodicals LLC: Pediatric Pulmonology. 2020; 55:3573-3578. DOI: 10.1002/ppul.25117
  9. M. Kamali Aghdam, M. Sadeghzadeh, S. Sadeghzadeh and K. Namakin. Challenges in A Child with Asthma and COVId-19. Elsevier Ltd. 2020. New Microbe and new Infections, Vol 37 Number C. Access : Challenges in a child with asthma and COVID-19 – ScienceDirect
  10. Elissa M. Abrams, MD, MPH, and Stanley J. Szefler, MD. Managing Asthma during Coronavirus Disease-2019: An Example for Other Chronic Conditions in Children and Adolescents. The Journal of Pediatrics. Vol 222. July 2020. Access: https://www.jpeds.com/article/S0022-3476(20)30528-X/fulltext
COVID-19 and DIABETES

COVID-19 and DIABETES

I have Diabetes, should I go for COVID-19 vaccination?

Covid-19 and Diabetes – In December 2019, a novel coronavirus, SARS-CoV-2, was identified as the pathogen  causing coronavirus disease (COVID-19) in Wuhan, China (11, 51, 55). On March 11, 2020, COVID-19 was declared a pandemic  by the World Health Organization. As of March 27, 2020, there have been a total of 103,942 confirmed cases with 1689 deaths in the United States. Globally, 27,324 deaths have been reported among 595,800 confirmed cases.

On 21st January 2021 there have been 95,612,831 confirmed cases of COVID-19, including 2,066,176 deaths, reported to WHO. As of January 2021, there have been 24.037.236 confirmed cases in the United States, 3.505.758 confirmed cases in the United Kingdom, 951.651 confirmed cases in Indonesia.

In 2019, approximately 463 million adults (20-79 years) were living with diabetes; by 2045 this will rise to 700 million. The proportion of people with type 2 diabetes is increasing in most countries 79% of adults with diabetes were living in low- and middle-income countries. 1 in 5 of the people who are above 65 years old have diabetes. 1 in 2 (232 million) people with diabetes were undiagnosed. Diabetes caused 4.2 million deaths. Diabetes caused at least USD 760 billion dollars in health expenditure in 2019 – 10% of total spending on adults. More than 1.1 million children and adolescents are living with type 1 diabetes. More than 20 million live births (1 in 6 live births) are affected by diabetes during pregnancy, 374 million people are at increased risk of developing type 2 diabetes.

Also Read Things People With Diabetes Must Know About the COVID-19 Vaccines

Diabetes is a serious threat to global health that respects neither socioeconomic status nor national boundaries. People living with diabetes are at risk of developing a number of serious and life-threatening complications, leading to an increased need for medical care, a reduced quality of life, and undue stress on families. Diabetes and its complications, if not well managed, can lead to frequent hospital admissions and premature death. Globally, diabetes is among the top 10 causes of death.

Source : Pusdatin Figure 1. Prevalence of Diabetes age 20-79 in 2019
covid-19 and diabetes
Source Pusdatin Figure 2. Top 10 countries with highest Diabetes in 2019

The genetic sequence of SARS-CoV-2 showed more than 80% shared identity to SARS-CoV and 50% to the MERS-CoV, and both SARS-CoV and MERS-CoV originate in bats and infect humans and wild animals. CoV is made up of four structural proteins: spike (S), membrane (M), nucleocapsid (N), and envelope (E) proteins. The S protein mediates receptor binding on the host cell membrane through the receptor-binding domain (RBD) in the S1 domain and membrane fusion through the S2 subunit. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV and SARSCoV-2, in contrast to MERS-CoV, which utilizes dipeptidyl peptidase 4 (DPP4) as its cellular receptor. This interaction thus determines host tropism and ultimately clearance of the virus. ACE2 is expressed in the upper respiratory system, type I and II alveolar epithelial cells in the lungs, the heart, endothelial cells, kidney tubular epithelium, enterocytes, and the pancreas. After binding to ACE2, proximal serine proteases such as TMPRSS2 are involved in S protein priming and cleavage of the spike. Proteases such as Furin subsequently release the spike fusion peptide, and the cellular virus enters through an endosomal pathway . The low pH and presence of proteases such as cathepsin-L  characteristic of the endosomal micro environment favor the delivery of SARS-CoV-2 genome into the cytosol  where further viral replication leads to the formation of mature virions and subsequent spread. Infected cells undergo apoptosis  or necrosis  and trigger inflammatory responses marked by the activation of proinflammatory cytokines or chemokines, which leads to the recruitment of inflammatory cells. CD4+ T helper (Th1) cells regulate antigen presentation and immunity against intracellular pathogens such as CoV through interferon gamma (IFN-ℽ) production. Th17 cells induce the recruitment of neutrophils and macrophages by producing interleukin-17 (IL-17), IL-21, and IL-22. SARS-CoV-2 infects circulating immune cells and increases apoptosis of lymphocytes (CD3, CD4, and CD8 T cells), leading to lymphocytopenia. Indeed, the degree of lymphocytopenia is associated with the severity of SARS CoV-2 infection. Lower T cell function relieves the inhibition on innate immune system leading to secretion of high amounts of inflammatory cytokines in what is known as a cytokine storm. In fact, circulating levels of cytokines/chemokines [IL-6, tumor necrosis factor-α (TNF)] and chemokines [CXC-chemokine ligand 10 (CXCL10) and CC-chemokine ligand 2 (CCL2)] involved in the cytokine storm syndrome are elevated and may play a role in SARSCoV-2-driven hyperinflammation leading to multiorgan failure.

Potential mechanisms that increase the risk of COVID-19 in diabetes. It is now well recognized that older age and the presence of diabetes, hypertension, and severe obesity (BMI =40 kg/m2 ) increase morbidity and mortality in patients with COVID-19. Considering the high prevalence of cardiovascular disease (CVD), obesity, and hypertension in patients with diabetes, it is unknown whether diabetes independently contributes to this increased risk. However, plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Potential mechanisms that may increase the susceptibility forCOVID-19 in patients with diabetes include: 1) higher affinity cellular binding and efficient virus entry, 2) decreased viral clearance, 3) diminished T cell function, 4) increased susceptibility to hyperinflammation and cytokine storm syndrome, and 5) presence of CVD. Augmented ACE2 expression in alveolar AT2 cells, muscle of the heart, kidney, and pancreas may favor increased cellular binding of SARS-CoV-2. Increased expression of ACE2 has been demonstrated in the lung, kidney, heart, and pancreas in rodent models of diabetes. Insulin  administration attenuates ACE2 expression, while hypoglycemic agents such as glucagon-like peptide-1 (GLP-1) agonists (liraglutide) and thiazolidinediones (TZDs; pioglitazone), antihypertensives such as ACE inhibitors, and statins upregulate ACE2. Until recently, whether diabetes was causally linked to ACE2 expression levels in the lung in humans was unknown.

covid-19 and diabetes
Source : ajpendo.org

Fig. 3. Cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The initial step in cellular entry of the virus is the binding of SARS-CoV-2 spike protein to cell surface angiotensin converting enzyme 2 (ACE2). Cellular proteases such as TMPRSS2 and furin are involved in priming of the S protein, which involves cleavage at the S1/S2 domains. This allows the fusion of the virus to the cell surface. Virions are taken up into endosomes, where SARS-CoV-2-S is cleaved and possibly activated by the pH-dependent cysteine protease cathepsin L. Once inside the cell, SARS-CoV-2 uses the endogenous cellular machinery to replicate itself. ACE catalyzes the conversion of angiotensin(Ang)ItotheoctapeptideAngII,whereasACE2 converts Ang II to Ang1–7. AngII through the activation of Ang II type 1a receptors induces vasoconstriction and proliferation,whereasAng1–7 stimulates vasodilatation and suppresses cell growth.

covid-19 and diabetes
Source : ajpendo.org

Fig. 4. Putative mechanisms contributing to increased susceptibility for coronavirus disease (COVID-19) in patients with diabetes mellitus (DM). Following aerosolized uptake of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invasion of the respiratory epithelium and other target cells by SARS-CoV-2 involves binding to cell surface angiotensin converting enzyme 2 (ACE2). Increased expression of ACE2 may favor more efficient cell binding and entry into cells. Early recruitment and function of neutrophils and macrophages are impaired in DM. Delay in the initiation of adaptive immunity and dysregulation of the cytokine response in DM may lead to the initiation of cytokine storm.

            There is a paucity of data in the world (including Indonesia) regarding comorbidities and COVID-19 outcomes and mechanism that modulate viral pathogenesis. But here is our mainly concern that people with comorbidities likely have chance to get COVID-19, so its mainly our concern that people with Diabetes should get vaccinated.

Several clinical reports have described greater morbidity and mortality from COVID-19 in people with diabetes, often accompanied by obesity. Most of this information is from individuals with type 2 diabetes, with less known about the risk in type 1 diabetes, a phenotypically distinct disorder. Experts have cautioned against extrapolating from studies of type 2 diabetes to individuals with type 1 diabetes. In the USA, the Centers for Disease Control and Prevention (CDC) currently categorize type 1 and type 2 diabetes differently in terms of risk for severe illness from COVID-19, with people with type 2 diabetes considered “at increased risk for severe illness” and those with type 1 diabetes categorized as “might be at increased risk”. Importantly, several recent studies have shown that both people with type 2 diabetes and those with type 1 diabetes have an increased vulnerability to serious illness from SARS-CoV-2 compared with people without diabetes. In relative terms, patients with type 1 diabetes and those with type 2 diabetes had similar adjusted odds ratios (ORs) for hospitalization (3·90 for type 1 diabetes vs 3·36 for type 2 diabetes), severity of illness (3·35 vs 3·42), and in-hospital mortality (3·51 vs 2·02). In a population-based study in Scotland, the risk of fatal or critical care unit treated COVID-19 was increased for both diabetes types (OR 2·4 with type 1 diabetes vs 1·4 with type 2 diabetes).

Source cdc.gov

Abbreviation: COVID-19 = coronavirus disease 2019.

* Data sources for each group: health care personnel (American Community Survey, 2019; ); long-term care facility residents (Minimum Data Set. Centers for Medicare & Medicaid Services; ); frontline and other essential workers (American Community Survey, 2019; ); age-specific groups (U.S. Census; ); high-risk medical conditions (Behavioral Risk Factors Surveillance System, 2018; ).

† Excludes persons who were recommended to receive vaccine in an earlier phase (e.g., persons aged 65–74 years who are living in long-term care facilities or who are health care personnel, who would have been included in Phase 1a) and accounting for overlap between groups within the same phase (e.g., essential workers with high risk medical conditions).

§ Estimates for frontline and other essential workers are approximate and derived from prepandemic survey data; relative proportions will vary by state.

¶ As of December 18, only the Pfizer-BioNTech COVID-19 vaccine is authorized for use in persons aged 16–17 years.

            Based on ongoing review of the literature, CDC has identified medical conditions or risk behavior that are associated with increased risk for severe COVID-19. The risk for COVID-19 associated hospitalization increases with the number of high-risk medical conditions, from 2,5 times the risk for hospitalization for person with one condition to 5 times the risk for those with three or more conditions.

            As we can see from the table above that Person aged 65-74years and Person aged 16-64years with high-risk medical conditions are included in Phase 1c to receive COVID-19 vaccine. So we conclude that person with diabetes are included in Phase 1c.

Indonesian Society of Internal Medicine(PAPDI) made the recommendations regarding COVID-19 vaccination (Sinovac) in patients with concomitant disease/comorbidities. People with diabetes are included to get vaccination which they described it all patient with controlled type 2 diabetes and HbA1C below 58 mmol/mol or 7,5%, vaccine can be given.

REFERENCES

  1. Ranganath Muniyappa and Sriram Gubbi. 2020. COVID-19 pandemic, coronaviruses, and diabetes melitus. American Physiological Society. doi:10.1152/ajpendo.00124.2020
  2. Who.int.(2021,22 January). WHO Coronavirus Disease (COVID-19) Dashboard.
  3. Infeksiemerging.kemkes.go.id(2021,22 January). COVID 19.
  4. idf.org(2021, 21 January). Internatinal Diabetes Federation: About Diabetes.
  5. kemkes.go.id.(2021, 21 January). Diabetes Melitus-Kementerian Kesehatan.
  6. Kathleen Dooling, MD, Mona Marin, MD, Megan Wallace, DrPH. 2021. The Advisory Committee on Immunization Practices’ Updated Interim Recommendation for Allocation of COVID-19 Vaccine -United States, December 2020. US Department of Health and Human Services/Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Report. Vol.69, No.51-52.
  7. Alvin C POwers, David M Aronoff, Robert H Ecked. 2021. COVID-19 vaccine prioritization for type 1 and type 2 diabetes. The Lancet Diabetes Endocrinal 2021. https://doi.org/10.1016/ S2213-8587(21)00017-6
  8. Papdi.or.id(2021, 22 January). Rekomendasi PAPDI tentang Pemberian Vaksinasi COVID-19.

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