A Real World Evaluation of the safety and immunogenicity of the Covishield vaccine, ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) in Health Care Workers (HCW) in National Capital Region (NCR) of India: A preliminary report

BackgroundThe SARS-CoV-2 pandemic has severely impacted health systems, economic and social progress globally in 2020. The rollout of vaccines in several parts of the world is being hailed as a solution to the crisis. With newer and more virulent serotypes on the horizon and limited vaccine available, evaluation of safety and immunogenicity is critical for rationalization of vaccine use in public health. ObjectiveTo evaluate real world safety, and, immunogenicity of the Covishield vaccine, ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) in Health Care Workers (HCW) during the national vaccine roll out in the NCR, New Delhi. The safety is evaluated through Adverse Events and Serious Adverse Events reported though enhanced pharmacovigilance protocols, and, the immunogenicity by quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 in serum samples collected before the receipt of the vaccine and 14 days after dose 1, using the fully automated LIAISON(R) SARS-CoV-2 S1/S2 IgG test using the chemiluminescence immunoassay (CLIA) ResultsIn the two weeks after immunization with the Covishield vaccine {ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant)}, none of the 1638 evaluated participants reported any serious adverse events (ie require hospitalization or emergency room visit). Solicited adverse events reported via daily diary cards included pain (62.7%) and soreness (24.1%) at injection site as most common, whereas fever (48.4%), headache (43.4%), myalgia (38.4%), fatigue (33.4%), joint pain (27.0%) and nausea (16.0%) were most common solicited systemic adverse events on day 1. Majority of local and systemic adverse events were seen in first 2 days post vaccination and thereafter they resolved. Lesser reactogenicity was observed in subjects with age >50 years. No major difference was observed in adverse events when subjects were stratified based on history of COVID 19 disease or baseline seropositivity. In our study serostatus improved from 48.2% positive at baseline to 79.0% positive 2 weeks following first dose of vaccination. After first dose of vaccination overall higher percentage (98.2%) of seropositivity rates were observed in those with past history of COVID 19 disease ConclusionThe Covishield vaccine {ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant)}, was safe and reported mild self limiting adverse events over 2-4 days and had an good early (within 2 weeks) seroresponse. This holds the promise of far reaching impact on vaccine availability for a larger population and thereby providing a widespread coverage.

Association of genetic polymorphisms with plasma TFPI level: Boon or curse for DVT patients - Study from India.

Low plasma TFPI levels have been associated with an increased risk of DVT; however its association with TFPI gene polymorphisms is controversial and not yet studied in India. The aim of our study was to analyze prevalence of TFPI gene polymorphisms, evaluate their effects on its plasma levels and determine its association with DVT. Plasma level and genetic polymorphisms (33T>C, 399C>T and 536C>T) of TFPI were screened in subjects (100 DVT patients and 100 controls). Mean TFPI level in patients was significantly lower than controls (Patients: 33.55±11.72ng/ml, Controls: 48.05±13.68ng/ml, p<0.001). DVT patients had significantly higher prevalence of 399C>T (p=0.001, ORa: 5.69, CI: 1.14-28.46) and lower prevalence of 33T>C polymorphism (p<0.001, ORa: 0.239, CI: 0.065-0.871). The wild type (TT genotype) of 33T>C and variant form (CT and TT genotype) of 399C>T polymorphism was significantly associated with low TFPI levels. TFPI 536C>T polymorphism was absent in all subjects. In conclusion, dual nature of TFPI gene polymorphisms were established in our association study; 33T>C being protective and 399C>T as an important risk factor in Indian DVT patients, probably mediated by alteration in TFPI levels. These findings may prove a vital role in risk stratification and treatment of DVT.

Aberrant myeloid antigen co-expression is correlated with high percentages of CD34-positive cells among blasts of acute lymphoblastic leukemia patients: an Indian tertiary care center perspective

BACKGROUND: Aberrant myeloid antigen (MA) co-expression and high expression of CD34 antigen on the blasts of acute lymphoblastic leukemia (ALL) patients are independently reported to have a role in pathogenesis and prognosis. This study was conducted to determine whether these two parameters are related. METHODS: A total of 204 cases of ALL were included in an analysis of blast immunophenotypic data. CD34 expression was categorized as low when less than 50% of blasts were CD34-positive (CD34low) and as high when 50% or more were CD34-positive (CD34high). RESULTS: Of 204 cases of ALL, 163 and 41 were of B-cell origin (B-ALL) and T-cell origin (T-ALL), respectively. Of all cases, 132 (64.7%) showed co-expression of MA and among these, 101 (76.51%) were CD34high, while the remaining 31 (23.48%) were CD34low. Of 72 cases without MA co-expression, 25 (34.72%) were CD34high and 47 (67.25%) were CD34low. Furthermore, of 163 cases of B-ALL, 111 showed co-expression of MA and 84 of these were CD34high. Of 52 cases of B-ALL without MA expression, 22 were CD34high. Among 41 cases of T-ALL, 21 co-expressed MA, 17 of which were CD34high. Moreover, all 20 cases of T-ALL without co-expression of MA were CD34low. These differences were statistically significant. CONCLUSION: We observed a strong correlation between aberrant MA expression and CD34high expression on the blasts of ALL. We hypothesize that these different patient subsets may represent unique prognostic characteristics.

Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum / 소아과

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients.

BACKGROUND: Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. OBJECTIVE: The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. METHODS: Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. RESULTS: An increased frequency of the GSTT1 null genotype (p-value = 0.05) was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. CONCLUSION: GST deletions do not play a direct role in iron overload of sickle cell patients.

Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients

BACKGROUND: Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. OBJECTIVE: The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. METHODS: Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. RESULTS: An increased frequency of the GSTT1 null genotype (p-value = 0.05) was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. CONCLUSION: GST deletions do not play a direct role in iron overload of sickle cell patients.

Genotypic influence of alpha-deletions on the phenotype of Indian sickle cell anemia patients

BACKGROUND: Some reports have shown that co-inheritance of alpha-thalassemia and sickle cell disease improves hematological parameters and results in a relatively mild clinical picture for patients; however, the exact molecular basis and clinical significance of the interaction between alpha-thalassemia and sickle cell disease in India has not yet been described. There is little agreement on the clinical effects of alpha-thalassemia on the phenotype of sickle cell disease. METHODS: Complete blood count and red cell indices were measured by an automated cell analyzer. Quantitative assessment of hemoglobin variants HbF, HbA, HbA2, and HbS was performed by high performance liquid chromatography (HPLC). DNA extraction was performed using the phenol-chloroform method, and molecular study for common alpha-deletions was done by gap-PCR. RESULTS: Out of 60 sickle cell anemia patients, the alpha-thalassemia genotype was found in 18 patients. Three patients had the triplicated alpha-genotype (Anti alpha-3.7 kb), and the remaining patients did not have alpha-deletions. This study indicates that patients with co-existing alpha-thalassemia and sickle cell disease had a mild phenotype, significantly improved hematological parameters, and fewer blood transfusions than the patients with sickle cell anemia without co-existing alpha-deletions. CONCLUSION: Co-existence of alpha-thalassemia and sickle cell anemia has significant effects on the phenotype of Indian sickle cell patients.