HLA-E*01:01 + HLA-E*01:01 genotype confers less susceptibility to COVID-19, while HLA-E*01:03 + HLA-E*01:03 genotype is associated with more severe disease.

BACKGROUND: HLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8+ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity. METHODS: 104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn't been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2. RESULTS: The absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 - 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 - 5.844) CONCLUSION: Here, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8+ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease.

Estimate of anti-SARS-CoV-2 spike IgG antibodies prevalence among Iranian population based on blood donations: A serial cross-sectional study during the third wave of the pandemic.

OBJECTIVES: Iran is one of the countries that have been confronted with the SARS-CoV-2 epidemic since February 2020. This study aimed to determine the levels of specific IgG antibodies against SARS-CoV-2 among healthy blood donors to estimate the burden of the epidemic. MATERIAL AND METHODS: A serial cross-sectional study was conducted on blood donors who referred to 31 main blood donation centers in different provinces during the third weeks of September, October, and November 2020. A questionnaire was filled out to collect socio-demographic characteristics, history of contact with COVID-19 patients, and history of COVID-19. A blood sample was collected from each participant to assess the antibodies against SARS-CoV-2 using the ELISA method. The crude prevalence of anti-SARS-CoV-2 IgG was calculated. Then it was weighted based on the gender and age groups of the general population in each province and adjusted for test sensitivity and specificity. RESULTS: During three time points of the study, 3840, 3697, and 3152 participants enrolled. The seroprevalence of SARS-CoV-2 IgG antibodies was 19.59% (17.18-22.00), 22.67% (20.70-24.65), and 32.63% (29.93-35.33) over the three rounds of the study. We found an association between the seropositivity and the highest educational level; AOR 0.76 (0.63-0.93), history of close contact with COVID-19 patients; AOR 1.69 (1.35-2.11), and history of confirmed SARS-CoV-2 infection; AOR 8.86 (5.38-14.60). CONCLUSION: This study showed that about one-third of the population had been infected with COVID-19. Furthermore, a significant upward trend in seroprevalence was observed. The predisposing factors indicate the importance of public health.

The impact of COVID-19 on blood safety and availability in the Islamic Republic of Iran.

Background: The COVID-19 pandemic has affected blood inventory and donation worldwide. The Islamic Republic of Iran was among the first countries to report the COVID-19 pandemic and it faced a significant blood shortage during the first weeks of the pandemic. Aims: We aimed to evaluate the impact of COVID-19 pandemic on the number, type, and safety of blood donations, comparing the periods before and during the pandemic. Methods: This retrospective study evaluated data from all volunteers who attended the blood transfusion centres in the Islamic Republic of Iran from March to December 2020 (during the COVID-19 pandemic) and during the same period in 2019, i.e. pre-pandemic. Data on the number of blood collections, confirmed transfusion transmissible infection marker test results, and donor demographic information were collected from the Iranian Blood Transfusion Organization integrated donor database. Results: Total blood donations decreased by 8.38%. The number of first-time, lapsed, and female blood donors increased by 4.41%, 0.17%, and 0.90% respectively. Regular blood donation decreased by 4.58%. The distribution of the 3 main blood products, red cell concentrate, frozen fresh plasma and platelets, decreased by 7.86%. All changes were statistically significant. The prevalence rates of hepatitis C virus and hepatitis B surface antigen increased significantly during the pandemic. Conclusion: COVID-19 had a negative effect on blood safety and availability in the Islamic Republic of Iran. To improve blood supply and enhance regular blood donation, the Iranian Blood Transfusion Organization needs to reassure blood donors of the safety and hygiene measures being observed at blood collection sites.

The potential effect of leukocyte filtration methods on erythrocyte-derived microvesicles: One step forward.

By harmonizing the pre-preparation conditions and also removing some donors' variations, the current study took one step forward to investigate whether different leukocyte filtration sets influence the quality of RBCs throughout the storage time. Twelve whole blood units were collected, and each unit was split into three equal parts. Thirty-six divided bags were filtered using three different leukocyte-filtration sets including Red Cell and Whole Blood Filters (12 units per filter). The prepared RBCs were refrigerated for up to 42 days and assessed for microvesicle count and size, clotting- and prothrombin time, hemolysis index, and biochemical parameters. A significant increment in erythrocytes microvesicle count (EMVs/µL) was observed during the time in the three filtration sets. The number of EMVs in WBF-RBCs was higher (~1.6 fold) than in F-RCF on day 42 (p=0.035). Interestingly the median fluorescence intensity of EMVs decreased during the storage. The size of MVs rose during the time without any significant differences among the filters. Coagulation time decreased in RBCs over the storage, with no significant differences among the filters. Hemolysis index and lactate concentration increased while glucose level decreased significantly throughout the time. The changes in WBF-RBCs were more drastic rather than RCF-RBCs. The only significant difference in the count of EMVs was between WBF and F-RCF components on day 42. Though the changes in WBF products were more drastic, all the values fell within the standard limits. Accordingly, all three filtration sets can be considered.

Positive anti-SARS-CoV-2 rapid serological test results among asymptomatic blood donors.

OBJECTIVES: The world is fighting with a COVID-19 pandemic, some of the uncertainties have been revealed. To figure out an estimation of asymptomatic patients and seropositive SARS-COV-2 blood donors in Iran, a national survey was conducted to find the prevalence of asymptomatic blood donors with positive SARS-COV-2 IgM/IgG test results at the end of May 2020. MATERIAL AND METHODS: From all 31 provinces, 1339 blood donors were included. At first, data was collected with an interview containing demographic data, risk factors and possible signs and symptoms held for each donor by a trained medical expert. Then, SARS-COV-2 serologic rapid tests were conducted. Subsequently, the test results were observed and recorded; all of their photos were checked by one single expert. We corrected the prevalence rates for sensitivity and weighted them by the last year rate of blood donation of each province. RESULTS: The corrected prevalence rates of positive serological test results for sensitivity in provinces were between zero and 38.24%. The national prevalence was calculated 14.45% after weighting. Out of 161 positive donors, only 43 cases reported related signs or symptoms during the defined period of time, while 118 (73.29%) seropositive cases had not reported any related signs or symptoms. Some signs or symptoms were reported more frequent in the SARS-COV-2 serologic rapid test positives. The highest OR (10.19) was linked to ageusia. CONCLUSIONS: This study has shown the prevalence of seropositive results to be around 14% in target population in which around ¾ had not reported any signs or symptoms.

The demographic and serological characteristics of COVID-19 convalescent plasma donors: Identification of basic criteria for optimal donor selection.

BACKGROUND AND OBJECTIVES: Convalescent plasma has attracted significant attention as a therapeutic option against infectious agents for more than a century. In March 2020, the use of Convalescent COVID-19 plasma (CCP) as a new research drug for COVID-19 treatment was approved by the FDA. The development of SARS-CoV-2 IgG antibodies following infection or vaccination is likely to be essential to provide adequate immunity for the population to halt the COVID19 pandemic. This study aimed to identify the criteria that would be used to determine the most appropriate CCP donors with the highest effective antiviral antibody titers. MATERIALS AND METHODS: In this prospective cohort, univariate analyses and multivariate regression analyses were performed to evaluate the relationship between characteristics of 11949 CCP donors and COVID-19 disease severity prior to donation with antibody titers estimated using ELISA technique and rapid tests. RESULTS: The antibody titer was measured among 8206 (68.7 %) donors. Elderly male and nulliparous female CCP donors who resided in the areas with high load of virus had positive ELISA and rapid test results as well as high levels of SARS-CoV-2 IgG antibodies titer. Moreover, the long hospital stay and elderly donors were the variables associated with high levels of SARS-CoV-2 IgG antibodies. CONCLUSION: This study suggests that nulliparous female and male donors with positive rapid tests who resided in areas with a higher prevalence of SARS-CoV-2, with more than 40 years of age and long hospitalization time can be the preferred donors for CCP donation.

Discrepancy between the results of one-stage and chromogenic factor VIII: C assays in patients with mild/moderate hemophilia A.

: Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity (FVIII:C) using the one-stage assay (OSA) or the two-stage chromogenic substrate assay (CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. The aim of this study was to assess the prevalence of FVIII:C assay discrepancy in non-severe hemophilia A patients in Iran and the relationship between the bleeding tendency with the level of FVIII:C by each method. Patients registered as mild or moderate hemophilia A in hemophilia clinic of Imam Khomeini Hospital were included. In each patient, FVIII:C level was assessed using one-stage (FVIII:C1) and chromogenic (FVIII:CR) methods. Assay discrepancy was defined as a two-fold or greater difference between the results of two assays. Bleeding tendency of the patients was recorded based on 'ISTH-BAT'. Sixty male patients were eligible for the study. The levels of FVIII:C1 was higher than FVIII:CR in 90% of patients. Assay discrepancy was seen in 41 (68%) patients. The classification of hemophilia A in 23 (38%) patients was modified by chromogenic method. No significant correlation was noted between the results of ISTH BAT with FVIII:C levels of each method. Regarding the prevalence of FVIII:C assay discrepancy in 2/3 of our non-severe hemophilia A patients, high rate of disease severity modification by chromogenic method and no significant relation between the clinical bleeding phenotype with any method, the authors highly recommend to perform both FVIII:C assays for the diagnosis and classification of non-severe hemophilia A.

Trends and epidemiological analysis of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and human T-cell lymphotropic virus among Iranian blood donors: strategies for improving blood safety.

BACKGROUND: Blood transfusion is associated with potential risks of transfusion-transmitted infections (TTIs). Different strategies are needed to monitor blood safety and screen the donors' efficacy, such as evaluation of the prevalence and trends of TTIs. This study was conducted to evaluate the prevalence and trends of TTIs, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV 1/2), and the impact of the donors' characteristics such as age, sex, and donor status on the prevalence of TTIs in blood donors in seven large provinces of Iran from 2010 to 2018. METHODS: This study was conducted on the data collected from all blood donations in seven Iranian Blood Transfusion Centers including Ardabil, Alborz, Guilan, West Azarbaijan, North, Razavi, and South Khorasan from April 2010 to March 2018. Demographic characteristics, number of donations, donor status, and screening and confirmatory serological results of all blood donations were collected from Iranian Blood Transfusion Organizations (IBTO) national database. The prevalence and trend of HBV, HCV, HIV, and HTLV 1/2 infections were reported according to the donation year and donor's characteristics. RESULTS: The analysis of the prevalence and trend of TTIs in 3,622,860 blood donors showed a significant decreasing trend in first-time and regular donors. Additionally, compared to first- time donors, regular donors made safer blood donations with lower risks of HBV, HIV, HCV and HTLV 1/2 (P < 0.0001). Although the prevalence of HTLV 1/2 and HBV was higher in females, TTIs had a significant decreasing trend in males and females. Finally, it was found that the prevalence of HBV and HTLV 1/2 increased with age up to 40-49 years and then decreased thereafter. CONCLUSIONS: The decreasing trends of TTIs in Iranian donors during 9 years may indicate that the various strategies implemented by IBTO have been effective in recent years. Other factors such as a decrease in the prevalence of specific TTIs in the general population might have also contributed to these declines.

Hepcidin gene polymorphisms and iron overload in ß-thalassemia major patients refractory to iron chelating therapy.

BACKGROUND: ß Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in ß-thalassemia major patients. METHODS: A total of 102 samples from ß thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher's exact test. RESULTS: A total of 102 adult ß-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T. CONCLUSIONS: Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients.

Patterns of topical corticosteroids prescriptions in children with asthma.

OBJECTIVES: To study topical corticosteroid use in Dutch asthmatic children using pharmacy dispensing data and to assess whether Dutch physicians prescribe topical corticosteroids in this population according to clinical guidelines. METHODS: Medication histories of children using asthma medication were extracted from the pharmacy dispensing system in 100 Dutch community pharmacies. The incidence rate and the potency of topical corticosteroid prescriptions per age were assessed. The topical corticosteroid incidence rates of the different age groups were compared using the Pearson chi-square test. Generalized linear models were used to study the prescription behavior of general practitioners and atopic dermatitis-related specialists regarding different classes of topical corticosteroids. RESULTS: Thirty percent of the infants received a topical corticosteroid prescription, compared with 15%-18% of the children aged 4 and older. Similarly, the mean number of topical corticosteroid prescriptions in infants was 2.2 per year, compared with 1.6-1.9 in children aged 4 and older. In concordance with the clinical guidelines, we observed that atopic dermatitis-related specialists more often prescribed first prescriptions of potent and very potent topical corticosteroids than general practitioners (relative risk = 2.55, 95% confidence interval = 1.79-3.63). Statistically significant differences (P < .01) were found between potencies of prescribed topical corticosteroids. CONCLUSION: Younger children receive more topical corticosteroid prescriptions than children aged 4 and older, and there is a statistically significantly higher prescription rate of topical corticosteroid for infants. Sometimes general practitioners do not follow guidelines and prescribe more-potent topical corticosteroids without a prior prescription of the same potency by a specialist.

The association between a genetic risk score for allergy and the risk of developing allergies in childhood-Results of the WHISTLER cohort.

BACKGROUND: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS) for allergy based on findings in adults and study its predictive capacity for allergy in children. METHODS: A GRS was constructed based on 10 SNPs previously associated with allergies in adults. The GRS was tested in children who participated in a population-based newborn cohort (WHISTLER) and were followed from birth to school age. Logistic regression analysis was used to study the association between the GRS and the parental-reported allergies at age 5 (based on a reported allergy to ≥1 of the following allergens: pollen, house dust mites, or pets). A Cox regression model was used to study the association between GRS and a physician-diagnosed allergy during follow-up (allergic conjunctivitis, allergic rhinitis, and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the agreement between physician-diagnosed allergy and parental-reported allergy at age 5. RESULTS: The GRS was significantly associated with parental-reported allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07-233.73) at age 5, as well as with a physician-diagnosed allergy during follow-up (hazard ratio: 1.89, 95% CI: 1.05-3.41). The overall agreement between physician-diagnosed and parental-reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03-0.18). CONCLUSIONS: An adult-derived GRS for allergy predicts the risk of developing allergies in childhood.

Early life antibiotic use and the risk of asthma and asthma exacerbations in children.

BACKGROUND: The use of antibiotic therapy early in life might influence the risk of developing asthma. Studies assessing the influence of early life antibiotic use on the risk of asthma exacerbations are limited, and the results are inconsistent. Therefore, the aim of this study was to assess the association between use of antibiotic during the first 3 years of life and the risk of developing childhood asthma and the occurrence of asthma exacerbations. METHODS: Data from four large childhood cohorts were used; two population-based cohorts to study the risk of developing asthma: Generation R (n=7393, The Netherlands) and SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma exacerbations: PACMAN (n=668, The Netherlands) and BREATHE (n=806, Scotland, UK). Odds ratios (ORs) were derived from logistic regression analysis within each database followed by pooling the results using a fixed- or random-effect model. RESULTS: Antibiotic use in early life was associated with an increased risk of asthma in a meta-analysis of the Generation R and SEATON data (OR: 2.18, 95% CI: 1.04-4.60; I2 : 76.3%). There was no association between antibiotic use in early life and risk of asthma exacerbations later in life in a meta-analysis of the PACMAN and BREATHE data (OR: 0.93, 95% CI: 0.65-1.32; I2 : 0.0%). CONCLUSION: Children treated with antibiotic in the first 3 years of life are more likely to develop asthma, but there is no evidence that the exposure to antibiotic is associated with increased risk of asthma exacerbations.

High incidence of oral corticosteroids prescriptions in children with asthma in early childhood.

OBJECTIVE: Severe asthma exacerbations are often treated with short courses of oral corticosteroids (OCS). This study assessed the incidence of OCS being prescribed in asthmatic children of various age groups and calculated their chances of receiving subsequent OCS prescriptions. METHODS: Longitudinal Dutch community pharmacy data of 2272 children who were regular users of asthma medication was analyzed retrospectively. Incidence rates for first, second and third prescriptions of OCS were calculated, stratified by age and sex. Probabilities of receiving first, second or third OCS prescriptions were assessed with Kaplan-Meier analysis. RESULTS: Incidence rates for first OCS prescriptions were 4.5 for the 1(st) year of life per 100 person-years (100PY); 3.9 for the 2(nd); 4.6 for the 3(rd); 4.2 for the 4(th), and 4.7 for the 5(th) year of life per 100PY. This was relatively high compared to incidence rates for children between the ages of 6 and 11 (ranging between 2.2 per 100PY (age 9) and 3.7(age 11)). Incidence rates for second and third OCS prescriptions were very high: 78.2(95%CI: 45.0-123.7) and 241.2(95%CI: 81.2-583.4) per 100PY for infants, respectively. The chances of receiving a first OCS prescription was higher in males (P value < 0.01). CONCLUSIONS: In the Netherlands, the incidence of OCS being prescribed to children being treated with asthma medication in early childhood is relatively high for first OCS prescriptions and extremely high for second and third OCS prescriptions compared to other ages. Furthermore, there is a high probability of receiving a further OCS prescription shortly after an OCS prescription.

Characteristics and severity of asthma in children with and without atopic conditions: a cross-sectional study.

BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions. METHODS: For this cross-sectional study, 703 children (ages 4 to 12 years) from the PACMAN cohort study were selected. All of the children were regular users of asthma medication. The study population was divided into nine subgroups according to parental-reported allergies of the child (hay fever, eczema, food allergy or combinations of these). In order to assess whether these subgroups differed clinically, the groups were compared for child characteristics (age, gender, family history of asthma), asthma exacerbations in the past year (oral corticosteroids (OCS) use; asthma-related emergency department (ED) visits), asthma control, fractional exhaled nitric oxide level (FeNO), and antihistaminic usage. RESULTS: In our study, 79.0% of the parents reported that their child suffered from at least one atopic condition (hay fever, food allergy and eczema), and one quarter of the parents (25.6%) reported that their child suffered from all three atopic conditions. Having more than one atopic condition was associated with an increased risk of OCS use (OR = 3.3, 95% CI = 1.6 - 6.6), ED visits (OR = 2.3, 95% CI = 1.2 - 4.6) in the past year and inadequate short term asthma control (OR = 1.9, 95% CI = 1.3 - 2.8). CONCLUSIONS: Children who use asthma medication often also have other allergic conditions. Parental reported allergies were associated with a higher risk of more severe asthma (more asthma complaints and more asthma exacerbations).