ABSTRACT
Background: The COVID19 disease has different outcomes ranging from asymptomatic disease to critically ill or even fatal outcomes in some people. This imposed the need for identification of early biomarkers that can predict the outcome. Previous studies show that VEGF-D has an important role in acute lung injury and acute respiratory distress syndrome, yet its role in COVID19 disease has not been evaluated thoroughly. Our study aimed to determine the possible use of VEGF-D as a predictor for COVID19 severity. Method(s): This is a retrospective study that includes 74 hospitalized patients with COVID19 in a period of one month at the University clinic for Infectious diseases and febrile conditions in Skopje. The patients were divided into two subgroups according to their outcome, a group of 45 patients with fatal outcome within the first week of hospitalization, and another group of 29 patients with mild COVID19 that required hospitalization less than 7 days without oxygen support. Sera samples were collected on the day of admission, and serological testing for human VEGF-D was performed using Quantikine ELISA Kit (R&D systems, Minneapolis, US). Result(s): The values measured for VEGF-D were 835.69+/-330.52 for the first group and 677.91+/-148.48 for the second. Student's t-test was performed, and it showed statistically significant difference between the groups;T test value = 2.413, p = 0.0183. The mean VEGF-D value in the group of patients with mild COVID19 is slightly above the reference range (153-642 pg/mL), while the group of patients with fatal outcome had significantly higher values. Conclusion(s): O ur f irst r esults i dentified V EGF-D a s a p ossible b iomarker for COVID19 severity. The significance of the test can be even of higher value, having in mind potential use of VEGF inhibitors as a treatment in COVID19 patients. The limitations of the study are the small sample size and variable time interval between symptom onset and hospital admission, so additional evaluation is planned on a larger cohort.
ABSTRACT
Background: Plasma collected from patients that have recovered from an infectious disease has been transfused over many decades for prophylaxis and treatment of various infectious diseases. Taking into consideration the expansion of COVID-19 pandemics, we started the COVID-19 convalescent plasma (CCP) programme. Aims: The aim of our study is to show our experience with collecting the CCP and to evaluate the SARS-CoV-2 antibody concentration in different convalescent plasma donors' subgroups. Methods: This is a prospective study performed in the Institute for Transfusion Medicine of Republic of North Macedonia since 30 April 2020 till July 2021. Antibody testing was performed at the Institute for Immunobiology and Human Genetics in Skopje using CLIA method with Snibe Maglumi SARS-CoV-2 S-RBD IgG (quantitative) with IgG cut-off larger than 5 AU/ml. All potential donor were tested for: negative RTPCR for SARSCoV-2 before donation, anti-SARS-CoV-2 antibodies, anti- HLA antibodies (where applicable), blood count, blood group, TTI and biochemistry. Preferred method for plasma collection was plasmapheresis which was performed with Terumo BCT Trima Accel and donation of whole blood, depending on the donor preference and venous access. All donors signed inform consent for donation and inclusion in the study. Results: There were 1476 potential CCP donors, but only 700(47.9%) donors fulfilled all the criteria and we obtained 793 units of CCP;639 (80.6%) units from whole blood donors and 154 (19.4%) CCP units from 61 plasmapheresis donors, 485 (69.3%) males and 215 (30.7%) females. Mean age of the donors was 40 years (range 18-63). Mean value of SARS-CoV-2 S-RBD IgG concentration was 31.05 AU/ml, (range from 5.1 AU/ml to >100 AU/ml), mean value of SARS-CoV-2 S-RBD IgG in men was 37.6 AU/ml and 28.9 AU/ml in women (p < 0.05). Distribution of CCP donors according to the ABO blood group was: 301 blood group A (43%) with median value of SARS-CoV-2 S-RBD IgG = 27.15 AU/ml, 220 blood group O (31.4%) median value of SARS-CoV-2 S-RBD IgG = 32.1 AU/ml, 116 blood group B (16.6%) median value of SARS-CoV-2 S-RBD IgG = 35.9 AU/ml and 63 donors had blood group AB (9%) median value of SARS-CoV-2 S-RBD IgG = 26.45 AU/ml. There were 69 donors that were previously hospitalized with mean value of SARS-CoV-2 S-RBD IgG = 48.6 AU/ml, and 629 that were treated at home with mean value of SARS-CoV-2 SRBD IgG = 29.1 AU/ml (p < 0.05), of which 578 had symptoms with mean value of SARSCoV- 2 S-RBD IgG = 29.1 AU/ml and 51 were asymptomatic with mean value of SARS-CoV-2 S-RBD IgG = 29.3 AU/ml. The CCP donors had the following distribution according to the age: 125 donors in the 18-29 age group with median value of SARS-CoV-2 S-RBD IgG = 23.0 AU/ml, 200 donors in the 30-39 age group with mean value of SARSCoV-2 S-RBD IgG = 28.2 AU/ml, 217 donors in the 40-49 age group with mean value of SARS-CoV-2 SRBD IgG = 32.9 AU/ml and 156 donors in the 50-63 age group mean value of SARS-CoV-2 S-RBD IgG = 38.3 AU/ml (p < 0.05). Summary/Conclusions: The collection procedures are safe and effective and collected CCP units were with high concentration and quality. The concentration of SARS-CoV-2 S-RBD IgG in CCP obtained from previously hospitalized patients was significantly larger than in ones that were treated at home. The concentration of SARS-CoV-2 S-RBD IgG was higher in men, in advanced age group and in donors with blood group B. The further studies are needed to clarify the impact of different variables on antibodies concentration/ titre in donors.
ABSTRACT
Background: Taking into consideration historic success of convalescent plasma in prophylaxis and treatment of various infectious diseases over the century and expansion of COVID-19 pandemics, we started the COVID-19 convalescent plasma program in our country. Aims: The aim of our study was to show the reasons for deferral of the COVID-19 convalescent plasma (CCP) donors. Methods: This is a prospective study organized in the Institute for Transfusion Medicine of Republic of North Macedonia since 30 April 2020 till July 2021. CCP donors eligible for donation were donors without a history of blood transfusion, female donors who have never been pregnant, or who have been tested and found negative for anti- HLA antibodies, age 18-65, in good health that fulfil all other criteria for regular blood donors. All potential donor were tested for: negative RT-PCR for SARSCoV-2 before donation, anti-SARS-CoV-2 antibodies, anti-HLA antibodies (where applicable), blood count, blood group, TTI and biochemistry. Antibody testing was performed at the Institute for Immunobiology and Human Genetics in Skopje using CLIA method with Snibe Maglumi SARS-CoV-2 S-RBD IgG with IgG cut-off for CCP donation larger than 5 AU/ml (cut-off for regular positive result was larger than 1 AU/ml). All donors signed inform consent for donation and inclusion in the study. Results: There were 1462 potential CCP donors, of which 762(52.1%) did not fulfil criteria for CCP donation, 424(55.6%) women and 338 (44.4%) men. There were 454(59.6%) potential CCP donors that did not have enough anti-SARS-CoV-2 S-RBD IgG antibodies (Ab), of which 223(49.1%) had Ab concentration less than 1 AU/ml (29.3% of all deferred donors) and 231(50.9%) had Ab concentration between 1 and 5 AU/ml (30.3% of all deferred donors). In this subgroup of deferred donors, there were 227 women (50%) and 227 men (50%), with mean age 37.2 ± 10.1 (range 18-63). There were statistical significant correlation between the gender and the Ab concentration less than 1 AU/ml and from 1 to 5 AU/ml (Pearson Chi-square: 3.88667, df = 1, p = 0.048671). Multiple regression analysis showed that gender is independently connected with the Ab concentration, OR = 1.4495 (95%CI 1.0016-2.0976), i.e. male gender increases the chance for increased Ab concentration for one and a half times. According to the age group, the majority of deferred CCP donors, because of low Ab concentration, are in the age group from 30 till 39(39.6%), followed by age group from 40 till 49(23.8%), and least deferred donors were in 50 and above age group (13.2%). The most of these deferred donors were treated at home, 451(99.3%) and had symptoms 240(52.9%). Distribution according to blood group in CCP donors deferred due to low Ab concentration was: blood group A- 182(40.1%), blood group O-153(33.7%), blood group B-69(15.1%) and blood group AB-42(9.3%). In the whole investigated group, 65 (8.5%) potential donors were deferred because of low haemoglobin level (less than 12.5 g/dl for women and less than 13.5 g/dl for men), 26 (3.4%) were deferred because of positive TTI markers and 102 (13.4%) women of the total number of deferred donors were deferred because of presence of HLA antibodies (i.e. 24% of investigated women). Summary/Conclusions: There is large percentage of deferred CCP donors mostly because of low Ab concentration, presence of HLA antibodies and low haemoglobin level, but starting of COVID-19 convalescent plasma program was a big success for our institution and our country and helped a lot of patients.