Re-positive PCR of SARS-CoV-2 in health care persons during COVID-19 pandemic.

Reinfection rate with SARS-CoV-2 and degree of protection by the induced antibody after the first episode of the infection is not well known, so it makes a big dilemma for health care personnel (HCP) who work in the front line of combating SARS-CoV-2. In this study, we investigated the frequency of SARS-CoV-2 redetection among HCP after the initial onset of the infection in a children's hospital during one year. Out of 131 seropositive HCP, 13.7% of them were symptomatic and PCR positive during 74-360 days after first sampling. Analysis of demographic data of seropositive HCP showed a correlation between a higher number of family members, higher body mass index, and the existence of underlying diseases with SARS-CoV-2 redetection. In conclusion, reinfection is one of the important problems in the SARS-CoV-2 pandemic. Research on this topic can help us to find answers to questions for estimating the duration of human protection with produced immunity after the infection or vaccination.

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.

Early high-titer convalescent plasma therapy in patients with moderate and severe COVID-19.

BACKGROUND AND OBJECTIVES: The use of COVID-19 convalescent plasma (CCP) has been approved by the FDA. We assessed the outcome of patients with moderate and severe COVID-19 following convalescent plasma therapy and the association with variables such as antibody titer in CCP units and transfusion time. MATERIALS AND METHODS: In this prospective cohort study, 3097 patients with moderate and severe COVID-19 (according to WHO Progression Scale) had heterogeneous demographic and clinical characteristics received plasma with an unknown titer at the transfusion time. Firstly, information about age, sex, blood group, the time interval from hospitalization to CCP transfusion, underlying disease, and antibody titer with the outcome were investigated. Then, multivariate logistic regression and area under the curve (AUC) were performed for the association between disease severity and intubation variables with transfusion time and outcome. RESULTS: Patients with younger age receiving CCP in the first five days of hospitalization had lower mortality (P < 0.0001). Moreover, patients without the underlying disease had lower mortality (P < 0.001). The mortality rate also decreased in severe patients who were intubated receiving CCP for less than five days (P < 0.001). In patients with moderate severity (score less than 5) who received IgG antibody levels above 1:320 in less than five days had lower mortality (P < 0.0001). CONCLUSION: Our findings suggested that COVID-19 patients with the moderate type of disease receiving CCP units with high antibody titers in the early stages of the disease experienced greater effectiveness of CCP therapy.

Clinical and genetic characteristics of hemoglobin H disease in Iran.

Hemoglobin H (Hb H) disease is a subtype of α-thalassemia caused by deletional and/or non-deletional mutations in three alpha-globin genes in which the various genotypes determine the disease severity. This study was aimed to investigate the frequency of alpha gene mutations and genotypes and their correlation with hematological and clinical characteristics in Iran. Among 202 patients diagnosed with Hb H disease through a national study in Iran according to standard methods, we had access to the hematologic and clinical findings and genetic data of 101 patients in whom genetic study was performed. Genomic DNA from peripheral blood was extracted and analyzed for identification of α-globin gene mutations using Multiplex Gap Polymerase Chain Reaction, Reverse Hybridization Assay, and finally Direct DNA Sequencing method. Twenty-one different mutations and thirty genotypes were detected in 101 patients with Hb H disease. In total, 39 patients (38.6%) were deletional and 62 patients (61.4%) were non-deletional type of the disease. The --MED mutation was highly prevalent in almost half of the patients (56.4%). Among various genotypes, -MED/-a3.7 (29.7%) and -α20.5/-α5NT (6.9%) were the most prevalent genotypes found in the studied group. Patients with non-deletional type presented with more severe hematological and clinical findings. Hb H percentage and serum ferritin levels were significantly higher in non-deletional patients in comparison to the deletional group (p < 0.05). 12 (11.9%) and 40 (39.6%) out of 101 patients were on regular and occasional transfusions, respectively. 83% of those with regular transfusion belonged to the non-deletional group. Among transfusion-dependent patients, -MED/αCSα and α20.5/-α5NT were the most common genotypes. In this study, two patients with -α20.5/αCSα and -MED/α-5NT genotypes experienced thrombotic events. This study indicated that although non-deletional genotypes of Hb H disease were responsible for more clinical severity of the disease, due to the presence of severe phenotypes even in deletional types, no definite correlation was found between genotype and phenotype.

Performance of a clinical risk prediction model for inhibitor formation in severe haemophilia A.

BACKGROUND: There is a need to identify patients with haemophilia who have a very low or high risk of developing inhibitors. These patients could be candidates for personalized treatment strategies. AIMS: The aim of this study was to externally validate a previously published prediction model for inhibitor development and to develop a new prediction model that incorporates novel predictors. METHODS: The population consisted of 251 previously untreated or minimally treated patients with severe haemophilia A enrolled in the SIPPET study. The outcome was inhibitor formation. Model discrimination was measured using the C-statistic, and model calibration was assessed with a calibration plot. The new model was internally validated using bootstrap resampling. RESULTS: Firstly, the previously published prediction model was validated. It consisted of three variables: family history of inhibitor development, F8 gene mutation and intensity of first treatment with factor VIII (FVIII). The C-statistic was 0.53 (95% CI: 0.46-0.60), and calibration was limited. Furthermore, a new prediction model was developed that consisted of four predictors: F8 gene mutation, intensity of first treatment with FVIII, the presence of factor VIII non-neutralizing antibodies before treatment initiation and lastly FVIII product type (recombinant vs. plasma-derived). The C-statistic was 0.66 (95 CI: 0.57-0.75), and calibration was moderate. Using a model cut-off point of 10%, positive- and negative predictive values were 0.22 and 0.95, respectively. CONCLUSION: Performance of all prediction models was limited. However, the new model with all predictors may be useful for identifying a small number of patients with a low risk of inhibitor formation.

Blood supply sufficiency and safety management in Iran during the COVID-19 outbreak.

BACKGROUND: COVID-19 first appeared in Iran on 19 February 2020, and then spread rapidly over the country. In this article, we review the action plan of the Iranian Blood Transfusion Organization with respect to this disease. METHOD AND MATERIALS: We collected data on blood donations and RBC inventory for the first 8 weeks of the outbreak. We also evaluated the trend of blood donations and RBC inventory and compared them with the data of the past year. We include a summary of actions taken by the National Committee on Management of COVID-19 outbreak. RESULTS: Blood donations decreased from 33 275 to 23 465 units during the first 2 weeks of the outbreak with a corresponding decrease in the RBC inventory. But after that, donations gradually increased from 23 465 to 29 665 units. RBC inventory levels improved at the same time. Then, the Iranian New Year's holiday resulted in another downward trend. After the holiday, blood donations revived, along with the RBC inventory. DISCUSSION: Although it appears that this virus cannot be transmitted through transfusion, changes in lifestyle had a significant impact on reducing blood supply. Following implemented measures, we saw an upward trend in blood donations and an adequate supply of RBC units in blood centres, helped by a reduction in demand by hospitals. Blood centres need to be more prepared to manage future viral disasters, especially in case of transfusion-transmissible infections.

Successful Splenectomy Management in a Patient With Moderate Factor VII Deficiency and Concomitant Severe Hereditary Spherocytosis.

By the advent of the effective therapies for many coagulation diseases and hereditary spherocytosis (HS), patient's survival has been improved significantly; however, if patients are diagnosed late or left untreated, both diseases could ominously be life threatening. Concurrent occurring of factor VII (FVII) deficiency and HS is extremely rare and there is no literature report that explain this condition, thus far. In this study, we confronted a 9-year-old female patient diagnosed with HS and enlarged spleen as a result of this blood disorder. Given to her sever signs and symptoms of splenomegaly, she was candidate for emergent splenectomy. However, assessment of coagulation tests revealed a prolonged prothrombin time, suggesting the moderate FVII deficiency. With a multidisciplinary consultation, we decided to performed total splenectomy with prophylaxis administration of totally 6 doses of active recombinant FVII, initiated 1 hour before surgery and followed until 30 hours postoperation. As a result of cautious undertaken in Mofid Children's Hospital, the patient did not experience any hemostatic defect. Patient is now 14-year-old, generally well-being under regular surveillance of FVII deficiency.

Hope in Iranian mothers of children with cancer: a descriptive correlational study.

PURPOSE: This study aims to examine the relationship between the level of hope in mothers who have a child with cancer and its related factors in Iran. METHOD: A cross-sectional and descriptive correlational design was used in this study. A demographic questionnaire and the Herth Hope Index (HHI) were administered to a sample of 240 mothers who have a child with cancer to assess level of hope. Mothers were also asked to indicate their highest priority hopes such as view of their supportive resources including financial support, psychosocial support, religiosity and spirituality. Data was analysed using descriptive statistics, Spearman's rho, independent sample t test and one-way ANOVA. RESULTS: The mean HHI score was 35.44 (n = 237). There was a positive correlation between HHI total score and spirituality (r = 0.267, P < 0.001), and psychosocial support (r = 0.281, P < 0.001). No significant differences were found between HHI total score and respondents who saw themselves as a religious person and the family financial support. There was a significant difference in HHI total scores for a mother who has a disabled child (M = 32.92, SD = 2.75; t (235) = 2.00, P = 0.046) and mothers of a child who do not have any disability besides their cancer (M = 35.59, SD = 4.91). No significant differences were found in the HHI total score and different group of the child's diagnoses and the mother's age or/and child's age. CONCLUSION: Mothers who have a child with cancer with better psychosocial and spiritual support showed a higher level of hope. A thorough knowledge of factors associated with hope in mothers caring for children suffering from cancer could provide a means to further advance the support delivered and the available resources given to the parents, especially the mothers.

Evaluation of Cytotoxic Potentials of Novel Cyclooxygenase-2 Inhibitor against ALL Lymphocytes and Normal Lymphocytes and Its Anticancer Effect through Mitochondrial Pathway.

In the present study, we searched selective cytotoxicity and mitochondria mediated apoptosis of novel COX-2 inhibitor 2-(4-(Methylsulfonyl)phenyl)imidazo[1,2-a] pyridine-8-carboxylic acid on B-lymphocytes and their mitochondria isolated from normal subjects and acute lymphoblastic leukemia (ALL) patients' blood. Our results showed this compound can selectively induce cellular and mitochondrial toxicity on ALL B-lymphocytes and mitochondria without any toxic effects on normal B-lymphocytes and their mitochondria. Taken together, the results of this study suggest that cancerous mitochondria are a potential target for the ALL B-lymphocytes. Selective toxicity of COX-2 inhibitor in cancerous mitochondria could be an attractive therapeutic option for the effective clinical management of therapy-resistant ALL.

Potential of therapeutic plasmapheresis in treatment of COVID-19 patients: Immunopathogenesis and coagulopathy.

Therapeutic plasmapheresis (TP) is the process of the separation and removal of plasma from other blood components and is considered as an adjunctive treatment strategy to the discarded abnormal agent in the management of respiratory viral pandemics. This article reviews the mechanisms of immunopathogenesis and coagulopathy induced by SARS-CoV-2 and the potential benefits of TP as adjunctive treatment in critically COVID-19 patients.

Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study.

Since Dec. 2019 the new coronavirus (SARS-CoV-2) has infected millions and claimed life of several hundred thousand worldwide. However, so far no approved vaccine or drug therapy is available for treatment of virus infection. Convalescent plasma has been considered a potential modality for COVID-19 infection. One hundred eighty-nine COVID-19 positive patients including 115 patients in plasma therapy group and 74 patients in control group, registered in the hospitals with confirmed COVID-19 infection, entered this multi-center clinical study. Comparison of outcomes including all-cause mortality, total hospitalization days and patients' need for intubation between the two patient groups shows that total of 98 (98.2 %) of patients who received convalescent plasma were discharged from hospital which is substantially higher compared to 56 (78.7 %) patients in control group. Length of hospitalization days was significantly lower (9.54 days) in convalescent plasma group compared with that of control group (12.88 days). Only 8 patients (7%) in convalescent plasma group required intubation while that was 20 % in control group. This clinical study provides strong evidence to support the efficacy of convalescent plasma therapy in COVID-19 patients and recommends this treatment for management of these patients. Clinical efficacy, immediate availability and potential cost effectiveness could be considered as main advantages of convalescent plasma therapy.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

Efficacy and safety of resveratrol, an oral hemoglobin F-augmenting agent, in patients with beta-thalassemia intermedia.

Recently, resveratrol showed induction of γ-globin mRNA synthesis in human erythroid precursors and reducing oxidative stress in red cells of thalassemia patients in many in vitro studies. We aimed to investigate the efficacy and safety of resveratrol, for the first time, in non-transfusion-dependent beta-thalassemia intermedia (B-TI) in Southern Iran. In this double-blind randomized clinical trial, 54 patients with B-TI were investigated during 6 months between October 2016 and March 2017. Patients were randomly allocated into three groups by simple randomization method. Group 1 (hydroxyurea (HU) and placebo, 18 patients), group 2 (resveratrol/piperine and placebo, 16 patients), and group 3(HU and resveratrol/piperine, 20 patients). Primary end point was considered as change in hemoglobin (Hb) levels and need for blood transfusion. Drug safety was considered as a secondary end point. Mean age of the patients was 28.2 ± 5.6 (18-42) years. Response rate was not significantly different among the three groups (P > 0.05). Higher percentages of adverse events were detected in groups 2 (31.3%) and 3 (25%) compared to group 1 (5.6%). However, the difference was not statistically significant (P > 0.05). All reported adverse events were gastrointestinal symptoms. Resveratrol showed a similar efficacy with HU in the small population of non-transfusion B-TI patients during a 6-month follow-up. Complications, mostly gastrointestinal, were observed more frequently in resveratrol groups compared to the HU group. Although it was not statistically significant, more attention should be given to safety and efficacy of resveratrol as an oral HbF-augmenting agent.

Modified Primary Prophylaxis in Previously Untreated Patients With Severe Hemophilia A in Iran.

BACKGROUND: Recently the low-dose tailoring method of primary prophylaxis has been introduced for previously untreated patients with hemophilia A. OBJECTIVE: To evaluate the efficacy and safety of low-dose tailoring method of primary prophylaxis in previously untreated patients with severe hemophilia A. MATERIALS AND METHODS: In this pre-post interventional study, 33 patients with severe hemophilia A who were previously untreated and affiliated to universities in the capital city and southern Iran were evaluated during 2014 to 2015. Modified primary continuous prophylaxis was used for patients with age below 3 years old, after first and before the second episodes of obvious clinical bleeding in large joints or large soft tissue hematoma or large amount of bleeding. Prophylaxis was started by 25 IU/kg once per week and increased to twice or 3 times a week according to defined bleeding events. RESULTS: The median age at diagnosis and age of starting prophylaxis were: 4 months (at birth, 22 mo) and 12 months (1 to 35 mo), respectively. Mean annual bleeding rate of patients after prophylaxis was 1.08±2.21 episodes per year. None of the patients had inhibitors before therapy. Inhibitor was present in 5 patients (15.1%) after prophylaxis. CONCLUSIONS: It seems that modified primary continuous prophylaxis has been successful in reducing bleeding episodes in children with severe hemophilia A and in the texture of lower cost it can improve quality of life of these patients, especially in developing countries where financial resources are limited.

Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: A longitudinal study.

BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy. METHODS: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory, and molecular data were collected. RESULT: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency in 11 (64.7%) patients. All patients had history of infectious complications; pneumonia was the most common (76.5%) occurring infection. A history of lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13 (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5), and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus treatment improved enteropathy of patients with remarkable success. The 20-year overall survival rate declined to 70.6%. CONCLUSION: LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.

Palliative Care for Children with Cancer in the Middle East: A Comparative Study.

INTRODUCTION: High incidence rates of childhood cancer and the consequent deaths in the Middle East is one of the major reasons for the need for palliative care in these countries. Using the experiences and innovations of the other countries can provide a pattern for the countries of the region and lead to the development of palliative care in children. Therefore, the aim of this study is to compare the status of pediatric palliative care in Egypt, Lebanon, Jordan, Turkey, and Iran. MATERIALS AND METHODS: This is a comparative study in which the information related to pediatric palliative care system in the target countries (from 2000 to 2016) has been collected, summarized, and classified by searching in databases, such as "PubMed, Scopus, Google scholar, Ovid, and science direct." RESULTS: Palliative care in children in the Middle East is still in its early stages and there are many obstacles to its development, namely, lack of professional knowledge, inadequate support of policy-makers, and lack of access to opioids and financial resources. Despite these challenges, providing services at the community level, support of nongovernmental organizations (NGOs), using trained specialists and multi-disciplinary approach is an opportunity in some countries. CONCLUSION: Considering the necessity of the development of pediatric palliative care in the region, solutions such as training the human resources, integrating palliative care programs into the curriculum of the related fields, establishing facilitating policies in prescription and accessibility of opioids, providing the necessary support by policy-makers, doing research on assessment of palliative care quality, as well as NGOs' participation and public education are suggested.

Health care resource utilization and cost of care for haemophilia A and B patients in Iran.

BACKGROUND: Despite the fact that the total therapeutic expenditure of haemophilia is paid by the national health system in Iran, a limited number of research has been performed to evaluate the economic burden of haemophilia. It is even more important when considering the fact that "prophylaxis" has never been used as the main treatment protocol in haemophiliacs in the country, causing high arthropathy rates. The aim of this study is to evaluate the cost drivers in the treatment of haemophilia A and B patients in Iran. METHODS: The national registry database of Ministry of Health (MoH) was queried to identify total number of individuals characteristics diagnosed with Factor VIII and IX deficiency. The service package defined by the department for special diseases was used as the reference for the type and frequency of health care utilization in haemophiliacs in Iran. The direct medical costs including prescription, medical intervention, inpatient, outpatient and diagnostics services and arthroplasty were considered. The prices were extracted from Iranian medical tariff book 2014-15. Medication cost was obtained from the Iranian Food and Drug Organization. RESULTS: Among 8,337 patients registered with bleeding disorders, 3,948 and 848 were identified with haemophilia A and B respectively, of whom 856 (18%) patients had inhibitor at any time in the past. In the two groups, 2,328 (59%) and 452 (53%) patients suffered from severe, 686 (17%) and 186 (22%) from moderate and 902 (23%) and 185 (22%) from mild type of haemophilia. The average annual health care cost for every patient was USD 15,130, mostly allocated to medication USD 10,180 (67%), followed by therapeutic services USD 4,775 (32%) while diagnostic services stood third USD 177 (1%). CONCLUSIONS: There is an urgent need for developing clinical practice guidelines for treatment protocols, procedures and supportive care in haemophilia management in Iran.

Factor XIII deficiency in Iran: a comprehensive review of the literature.

Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern country with a high rate of consanguineous marriages, there are approximately 473 patients afflicted with FXIIID. An approximately 12-fold higher prevalence of FXIIID is estimated in Iran in comparison with overall worldwide frequency. In this study, we have undertaken a comprehensive review on different aspects of FXIIID in the Iranian population. The distribution of this disease in different regions of Iran reveals that Sistan and Baluchestan Province has not only the highest number of patients with FXIIID in Iran but the highest global incidence of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and prolonged wound bleeding are the most frequent clinical manifestations. There are several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg being the most common mutation in FXIIID in Iran. Traditionally, the management of FXIIID in Iran was only based on administration of fresh frozen plasma or cryoprecipitate, until 2009 when FXIII concentrate became available for patient management. Various studies have evaluated the efficacy and safety of prophylactic regimens in different situations with valuable findings. Although the focus of this study is on Iran, it offers considerable insight into FXIIID, which can be applied more extensively to improve the management and quality of life in all affected patients.