Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation.

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years.

Objective: To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). Methods: This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). Results: A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). Conclusion: The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years / Programa de control externo de la calidad en el tamizaje de enfermedades infecciosas en laboratorios y bancos de sangre de América Latina: análisis de los últimos 5 años / Programa externo de controle de qualidade na triagem de doenças infecciosas em laboratórios e bancos de sangue da América Latina: análise dos últimos 5 anos

[ABSTRACT]. Objective. To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). Methods. This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). Results. A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). Conclusion. The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

[RESUMEN]. Objetivo. Evaluar el tamizaje de muestras de sangre en las que se analizan marcadores de enfermedades infecciosas en laboratorios y bancos de sangre de América Latina según los resultados de un programa de evaluación externa de la calidad (EQAP, por su sigla en inglés). Métodos. Este análisis cualitativo utilizó datos del EQAP —coordinado por la Fundação Pro Sangue Hemocentro de São Paulo con el apoyo de la Organización Panamericana de la Salud— para evaluar la eficacia del tamizaje sanguíneo para la detección de enfermedades infecciosas que se realizó entre el 2014 y el 2018 en América Latina. Cada laboratorio o banco de sangre participante recibió un panel idéntico para análisis a ciegas compuesto por 24 muestras de sangre con reactividad variable para todos los parámetros del tamizaje. Los paneles se procesaron en cada establecimiento participante y los resultados se enviaron a la Fundação Pro Sangue Hemocentro de São Paulo donde se realizaron análisis individuales y conjuntos. Había dos tipos de resultados discrepantes que eran posibles fallas del tamizaje: los positivos falsos (PF) y los negativos falsos (NF). Resultados. En total se evaluaron 23 136 muestras. Las tasas generales de PF, NF y resultados concordantes fueron, respectivamente, del 0,3%, 1,0% y 98,7%. Se obtuvieron siete NF en casos de HBsAg (1,0%), 12 en casos de sífilis (2,6%) y 21 en casos de enfermedad de Chagas (2,9%). No se obtuvieron NF en casos de infección por virus del VIH, el VHC o el VLTH. La precisión promedio de todos los laboratorios y bancos de sangre participantes en el EQAP durante el periodo de estudio fue del 99,5% (desviación típica: 0,5%). Conclusión. Los resultados de este análisis cualitativo son positivos en lo referente a la seguridad sanguínea en América Latina, con una precisión promedio del 99,5% entre los laboratorios y bancos de sangre participantes. Este informe refleja la considerable mejora del tamizaje serológico que se realiza en los bancos de sangre, en comparación con los resultados del informe del EQAP que contó con el apoyo de la OPS y se publicó en el 2003.

[RESUMO]. Objetivo. Avaliar a triagem de marcadores de doenças infecciosas em amostras de sangue realizada em laboratórios e bancos de sangue da América Latina de acordo com os resultados de um Programa Externo de Avaliação de Qualidade (EQAP, na sigla em inglês). Métodos. Esta análise qualitativa usou dados do EQAP coordenado pela Fundação Pró-Sangue Hemocentro de São Paulo, com o apoio da Organização Pan-Americana da Saúde, para avaliar o desempenho da triagem de sangue quanto a doenças infecciosas no período de 2014 a 2018 na América Latina. Cada laboratório ou banco de sangue participante recebeu um painel cego idêntico com 24 amostras de sangue de reatividade variável para todos os parâmetros de triagem. Os painéis foram processados em cada estabelecimento participante e os resultados foram devolvidos à Fundação Pró-Sangue Hemocentro de São Paulo para análises individuais e conjuntas. Dois tipos de resultados discrepantes representavam falhas em potencial: resultados falso-positivos e resultados falso-negativos (não reativos). Resultados. Foram avaliadas 23.136 amostras. As taxas globais de resultados falso-positivos, falso-negativos e concordantes foram de 0,3%, 1,0% e 98,7%, respectivamente. Foram encontrados sete resultados falso-negativos para HBsAg (1,0%), 12 para sífilis (2,6%) e 21 para doença de Chagas (2,9%). Não houve resultados falso-negativos para os vírus HIV, HCV e HTLV. A acurácia média de todos os laboratórios e bancos de sangue que participaram do EQAP durante o período do estudo foi de 99,5% (desvio padrão de 0,5%). Conclusões. Os resultados desta análise qualitativa são positivos para a segurança do sangue na América Latina, com uma acurácia média de 99,5% entre os laboratórios e bancos de sangue participantes. Este rela- tório reflete uma melhoria importante na triagem sorológica dos bancos de sangue em relação aos resultados do relatório do EQAP apoiado pela OPAS que foi publicado em 2003.

Natural killer cells 56bnght16- have higher counts in the umbilical cord blood than in the adult peripheral blood

ABSTRACT Introduction and hypothesis: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for allogeneic hematopoietic stem cell transplantation in the absence of a compatible donor. The UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD), but is associated with slower engraftment and slower immune reconstitution, compared to other sources. Dendritic cells (DCs) and Natural Killer cells (NKs) play a central role in the development of GvHD and the graft versus leukemia (GvL) effect, as well as in the control of infectious complications. Method: We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DCs, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. Results: In the UCB samples, there were higher counts of NK cells 56bright16- (median 0.024 × 109/L), compared to the PB samples (0.012 × 109/L, p < 0.0001), NK 56dim16bright (median 0.446 × 109/L vs. 0.259 × 109/L for PB samples, p = 0.001) and plasmacytoid dendritic cells (pDCs, median 0.008 × 109/L for UCB samples vs. 0.006 × 109/L for PB samples, p = 0.03). Moreover, non-classic monocyte counts were lower in UCB than in PB (median 0.024 × 109/L vs. 0.051 × 109/L, respectively, p < 0.0001). Conclusion: In conclusion, there were higher counts of NK cells and pDCs and lower counts of non-classic monocytes in UCB than in PB from healthy individuals. These findings might explain the lower incidence and severity of chronic GvHD, although maintaining the GvL effect, in UCB transplant recipients, compared to other stem cell sources.

Detection of unreported usage of the antiretroviral drug lamivudine in two blood donors.

BACKGROUND: Unreported HIV antiretroviral (ARV) drug usage by blood donors compromises the ability to detect evidence of HIV infection in blood screening tests and represents a risk for blood transfusion safety. Our objective was to determine the frequency of undeclared ARV drug use by blood donors with altered HIV markers. STUDY DESIGN AND METHODS: This was a retrospective cross-sectional analysis of donations that were tested for HIV antibody (ab), antigen (ag), and RNA by chemiluminescent immunoassay and nucleic acid screening tests. Positive samples were retested and were subjected to ARV drug testing by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Of 345,252 blood donations, 361 (0.1%) were positive on initial testing. Samples from 296 (81.9%) of these donations were available for further analysis. The presence of HIV ab/ag and/or RNA was confirmed in 83 (28.0%) of these samples. All 296 bloods were subjected to ARV testing. The ARV drug lamivudine, at 11.3 and 6.7 ng/mL, was detected in 2 of 83 (2.4%) donations that were HIV positive. Other drugs were not detected. CONCLUSION: Unreported ARV usage was identified in two candidates for blood donation. More intensive efforts to educate donors about disclosure and to investigate the extent of this phenomenon in Brazil are needed.

Evaluation of Dengue, Zika virus, and Chikungunya virus transmission by blood components in recipients of haematopoietic stem cell transplantation.

BACKGROUND: Brazil has a high prevalence of arboviruses, especially Dengue (DENV), Zika (ZKV), and Chikungunya (CHKV). OBJECTIVES: To study the risk of DENV, ZKV, and CHKV transmission by blood components in the haematopoietic stem cell transplantation (HSCT) population. METHODS: Prospective cohort of HSCT recipients and donors performed at the Hospital das Clinicas da FMUSP, São Paulo-Brazil. Patients were evaluated by serology and RT-PCR for DENV, ZKV, and CHKV pre-transplantation and once a week until neutrophil grafting. In positive cases (positive RT-PCR and/or serology conversion), an investigation was carried out on the blood components that the patient received to evaluate the possibility of it being transfusion transmitted. RESULTS: A total of 93 patients were included during the study period. The mean age was 52 years with a predominance of males (56.9%). We considered five (5.3%) DENV cases positive by seroconversion in our study. One patient had IgM seroconversion and the other four presented IgG seroconversion to DENV. In the investigation of the blood components, 145 individual samples were analysed. None of the investigated blood components showed a positive RT-PCR. CONCLUSION: We observed a low prevalence of DENV, ZKV, and CHKV in HSCT donors and recipients by serology and RT-PCR, and no case of blood transfusion transmission by RT-PCR.

Surveillance for Zika, Chikungunya, and Dengue Virus Incidence and RNAemia in Blood Donors at 4 Brazilian Blood Centers During 2016-2019.

BACKGROUND: Except for public health case reports, the incidence of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) infection are not available to assess the potential blood transfusion safety threat in Brazil. METHODS: Pools of 6 donation samples (MP6) left over from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus nucleic acid testing were combined to create MP18 pools (3 MP6 pools). Samples were tested using the Grifols triplex ZIKV, CHIKV, and DENV real-time transcription mediated amplification assay to estimate prevalence of RNAemia and incidence, and to compare these results to case reports in São Paulo, Belo Horizonte, Recife, and Rio de Janeiro, from April 2016 through June 2019. RESULTS: ZIKV, CHIKV, and DENV RNAemia were found from donors who donated without overt symptoms of infection that would have led to deferral. The highest RNAemic donation prevalence was 1.2% (95% CI, .8%-1.9%) for DENV in Belo Horizonte in May 2019. Arbovirus infections varied by location and time of year, and were not always aligned with annual arbovirus outbreak seasons in different regions of the country. CONCLUSIONS: Testing donations for arboviruses in Brazil can contribute to public health. Transfusion recipients were likely exposed to ZIKV, CHIKV, and DENV viremic blood components during the study period.

Improved detection of hepatitis C virus-positive blood donors and determination of infection status.

BACKGROUND: In low-risk populations, variability in the sensitivity of current serological tests for Hepatitis C virus (HCV) blood donor screening may lead to the presence of false-positive results. This contributes to the unnecessary loss of blood donor samples as well as to difficulty in accurate donor counselling. The present study determined the optimal cut-off value of a chemiluminescent immunoassay for identification of HCV-reactive blood donors. STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis of 193 973 blood donations, 578 samples that were positive for HCV antibody in a chemiluminescent immunoassay and/or RNA screening tests were identified. Blood from 379 of these positive samples was available for retesting by a second confirmatory HCV immunoassay followed by a receiver operating characteristic (ROC) curve analysis. Donors were also recalled for a new analysis. RESULTS: Only 71 (18.7%) blood samples remained HCV-positive upon retesting, while 233 (61.5%) now tested negative and 75 (19.8%) yielding indeterminate results. A signal to cutoff ratio ≥4.32 was determined as the best differential threshold between a positive and negative result, increasing the positive predictive value from 27.3% to 66.7%. CONCLUSION: Using a higher threshold for an HCV-positive blood sample enhances the chemiluminescent immunoassay screening test´s accuracy and helps to improve donor counselling and notification processes.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years / Programa de control externo de la calidad en el tamizaje de enfermedades infecciosas en laboratorios y bancos de sangre de América Latina: análisis de los últimos 5 años / Programa externo de controle de qualidade na triagem de doenças infecciosas em laboratórios e bancos de sangue da América Latina: análise dos últimos 5 anos

ABSTRACT Objective. To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). Methods. This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). Results. A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). Conclusion. The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

RESUMEN Objetivo. Evaluar el tamizaje de muestras de sangre en las que se analizan marcadores de enfermedades infecciosas en laboratorios y bancos de sangre de América Latina según los resultados de un programa de evaluación externa de la calidad (EQAP, por su sigla en inglés). Métodos. Este análisis cualitativo utilizó datos del EQAP —coordinado por la Fundação Pro Sangue Hemocentro de São Paulo con el apoyo de la Organización Panamericana de la Salud— para evaluar la eficacia del tamizaje sanguíneo para la detección de enfermedades infecciosas que se realizó entre el 2014 y el 2018 en América Latina. Cada laboratorio o banco de sangre participante recibió un panel idéntico para análisis a ciegas compuesto por 24 muestras de sangre con reactividad variable para todos los parámetros del tamizaje. Los paneles se procesaron en cada establecimiento participante y los resultados se enviaron a la Fundação Pro Sangue Hemocentro de São Paulo donde se realizaron análisis individuales y conjuntos. Había dos tipos de resultados discrepantes que eran posibles fallas del tamizaje: los positivos falsos (PF) y los negativos falsos (NF). Resultados. En total se evaluaron 23 136 muestras. Las tasas generales de PF, NF y resultados concordantes fueron, respectivamente, del 0,3%, 1,0% y 98,7%. Se obtuvieron siete NF en casos de HBsAg (1,0%), 12 en casos de sífilis (2,6%) y 21 en casos de enfermedad de Chagas (2,9%). No se obtuvieron NF en casos de infección por virus del VIH, el VHC o el VLTH. La precisión promedio de todos los laboratorios y bancos de sangre participantes en el EQAP durante el periodo de estudio fue del 99,5% (desviación típica: 0,5%). Conclusión. Los resultados de este análisis cualitativo son positivos en lo referente a la seguridad sanguínea en América Latina, con una precisión promedio del 99,5% entre los laboratorios y bancos de sangre participantes. Este informe refleja la considerable mejora del tamizaje serológico que se realiza en los bancos de sangre, en comparación con los resultados del informe del EQAP que contó con el apoyo de la OPS y se publicó en el 2003.

RESUMO Objetivo. Avaliar a triagem de marcadores de doenças infecciosas em amostras de sangue realizada em laboratórios e bancos de sangue da América Latina de acordo com os resultados de um Programa Externo de Avaliação de Qualidade (EQAP, na sigla em inglês). Métodos. Esta análise qualitativa usou dados do EQAP coordenado pela Fundação Pró-Sangue Hemocentro de São Paulo, com o apoio da Organização Pan-Americana da Saúde, para avaliar o desempenho da triagem de sangue quanto a doenças infecciosas no período de 2014 a 2018 na América Latina. Cada laboratório ou banco de sangue participante recebeu um painel cego idêntico com 24 amostras de sangue de reatividade variável para todos os parâmetros de triagem. Os painéis foram processados em cada estabelecimento participante e os resultados foram devolvidos à Fundação Pró-Sangue Hemocentro de São Paulo para análises individuais e conjuntas. Dois tipos de resultados discrepantes representavam falhas em potencial: resultados falso-positivos e resultados falso-negativos (não reativos). Resultados. Foram avaliadas 23.136 amostras. As taxas globais de resultados falso-positivos, falso-negativos e concordantes foram de 0,3%, 1,0% e 98,7%, respectivamente. Foram encontrados sete resultados falso-negativos para HBsAg (1,0%), 12 para sífilis (2,6%) e 21 para doença de Chagas (2,9%). Não houve resultados falso-negativos para os vírus HIV, HCV e HTLV. A acurácia média de todos os laboratórios e bancos de sangue que participaram do EQAP durante o período do estudo foi de 99,5% (desvio padrão de 0,5%). Conclusões. Os resultados desta análise qualitativa são positivos para a segurança do sangue na América Latina, com uma acurácia média de 99,5% entre os laboratórios e bancos de sangue participantes. Este relatório reflete uma melhoria importante na triagem sorológica dos bancos de sangue em relação aos resultados do relatório do EQAP apoiado pela OPAS que foi publicado em 2003.

Transfusion-Acquired HIV: History, Evolution of Screening Tests, and Current Challenges of Unreported Antiretroviral Drug Use in Brazil.

Prevention of HIV acquisition by blood transfusion from its emergence to the present day is reviewed, and current challenges are delineated. The experience of Fundação Pró-Sangue/Hemocentro de São Paulo, Brazil, is highlighted in the quest for improvements in blood safety and the evolution of increasingly sensitive and specific screening tests. Concerns and establishing stringent criteria in the screening of potential blood donors are emphasized, and the current criteria for identifying and deferring candidates at high risk of acquiring sexually transmitted diseases are summarized. Future challenges relate to the identification of donors with unreported use of antiretroviral drugs for prophylaxis against possible HIV exposure or for treatment of an HIV infection whose viral expression is undetectable by current analyses. There is a need to better understand the motivation of HIV-exposed donors and to educate them about the risk of transfusion-mediated HIV transmission despite having low or undetectable viral loads. In situations in which traditional HIV RNA or antibody detection assays remain negative, more sensitive analyses are needed to identify potential donors at risk for HIV transmission.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.

Impact of HLA-G +3142C>G on the development of antibodies to blood group systems other than the Rh and Kell among sensitized patients with sickle cell disease.

BACKGROUND: Patients' inflammatory history is an important factor underlying red blood cell (RBC) alloimmunization, which is a frequent transfusion complication among individuals with sickle cell disease (SCD). HLA-G has been associated with different inflammatory and auto - immune diseases. Our goal was to verify whether the HLA-G + 3142 C>G and 14-bp Ins/Del variations are associated with RBC antibody development among SCD patients. METHODS: This was a single-center case-control study. SCD patients were randomly selected for the study and divided into two groups: 'Alloimmunized' and 'Nonalloimmunized' depending on the presence of irregular antibodies. The 'Alloimmunized'group was further divided into two subgroups according to the presence of only antibodies against the Rh and Kell blood group systems or the existence of antibodies to antigens of the other blood group systems. RESULTS: A total of 213 patients were included in the study (110 alloimmunized and 103 non-alloimmunized). The 'Alloimmunized' and 'Non-alloimmunized' groups did not differ statistically regarding the HLA-G + 14 bp Ins/Del ( p = 0.494) and + 3142 C>G ( p = 0.334). Individuals who had only antibodies against the Rh and Kell antigens had a frequency of HLA-G + 3142GG genotype almost twice as high compared to the groupwith antibodies against less immunogenic antigens ( p = 0.043). CONCLUSIONS: The genotype frequency of HLA-G + 3142 C>G differs among alloimmunized SCD patients, depending on the presence of antibodies against low immunogenic RBC antigens. This highlights a possible role played by the HLA-G molecule in the RBC alloimmunization process.

Development and implementation of a COVID-19 convalescent plasma program in a middle-income economy

Abstract Introduction Convalescent Plasma therapy is one of the therapeutic strategies that has been used for patients with the Covid-19 disease. Implementing a program with national extension to supply hospitals with this blood component is a great challenge mainly in a middle-income economy. Objectives Our objective was to develop and implement a Covid-19 Convalescent Plasma Program which met established quality standards and was adapted to a reality of limited resources. Methods A multicentric convalescent plasma collection program was developed and implemented, based on four main sequential procedures: selective donor recruitment, pre-donation antibody screening (Anti-SARS-CoV-2- Chemiluminescence IgG Abbott), convalescent plasma collection by apheresis or whole-blood processing and distribution to the hospitals according to local demand. Results From the 572 candidates submitted to the pre-donation antibody screening, only 270 (47%) were considered eligible for plasma donation according to the established criteria. Higher levels of total antibody were associated with the donor age being above 45 years old (p= 0.002), hospital admission (p= 0.018), and a shorter interval between the diagnosis of the SARS-CoV-2 infection and plasma donation (p < 0.001). There was no association between the ABO and Rh blood groups and their antibody levels. Of the 468 donations made, 61% were from the collection of whole-blood and 39%, from apheresis. The Covid-19 Convalescent Plasma units obtained were distributed to 21 different cities throughout the country by air or ground transportation. Conclusion The implementation of a Covid-19 Convalescent Plasma program in a continental country with relatively scarce resources is feasible with alternative strategies to promote lower cost procedures, while complying with local regulations and meeting quality standards.

Association between FY* 02N. 01 and the severity of COVID-19: initial observations

ABSTRACT Introduction The pro-inflammatory immune response underlies severe cases of COVID-19. Antigens of the Duffy blood group systems are receptors for pro-inflammation chemokines. The ACKR1 c.-67T>C gene variation silences the expression of Duffy antigens on erythrocytes and individuals presenting this variant in homozygosity have impaired inflammatory response control. Our aim was to evaluate the association between the ACKR1 c.-67T>C and the severity of COVID-19. Methods This was a retrospective single-center case-control study, enrolling 164 participants who were divided into four groups: 1) Death: COVID-19 patients who died during hospitalization; 2) Hospital Discharge: COVID-19 patients who were discharged for home after hospitalizations; 3) Convalescent Plasma Donors: COVID-19 patients who were not hospitalized, and; 4) Controls: patients with diagnosis other than COVID-19. Patients were genotyped for the ACKR1 c.-67T>C (FY*02 N.01 allele) and the frequency of individuals presenting the altered allele was compared between the groups. Results The groups significantly differed in terms of the percentage of patients presenting at least one FY*02N.01 allele: 36.8% (Death group), 37% (Hospital Discharge group), 16.1% (Convalescent Plasma group) and 16.2% (Control group) (p= 0.027). The self-declared race (p < 0.001) and the occurrence of in hospital death (p= 0.058) were independently associated with the presence of the FY*02N.01 allele. Hypertension (p < 0.001), age (p < 0.001) and the presence of at least one FY*02N.01 allele (p= 0.009) were independently associated with the need for hospitalization. Conclusion There is a suggestive association between the presence of the FY*02N.01 and the severity of COVID-19. This may be a mechanism underlying the worse prognosis for Afro-descendants infected with SARS-CoV-2.

The impact of immediate adverse donation reactions on the return of volunteers undergoing platelet apheresis.

INTRODUCTION: Immediate adverse reactions experienced during donation decrease return rates among whole-blood donors, but little is known about this effect among platelet apheresis donors. We investigated the impact of immediate adverse reactions on the return rates of volunteer apheresis platelet donors. METHODS: In a sample of 4108 consecutive platelet apheresis donors seen from August 2016 through June 2019, we evaluated whether immediate adverse reactions were associated with returning for a subsequent platelet apheresis donation within a 12-month period. We used propensity score matching to compare donors with and without adverse reactions. RESULTS: An immediate adverse reaction occurred in 312 (7.6%) donors; 98.5% were mild, and 0.3% were severe. Of the original 4108 platelet apheresis donors, only 3211 (72.3%) returned for a subsequent donation within 12 months. Experiencing an immediate adverse reaction during the donation process significantly decreased the return rate for a subsequent donation [HR= 0.74 (0.63-0.87)], especially among female donors [HR= 0.70 (0.53-0.93)], donors aged < 30 years [HR= 0.71 (0.54-0.94)], with a high school educational level [0.63 (0.49-0.81)], donors donating for the first time [HR= 0.73 (0.59-0.90)], and repeat donors with a previous platelet apheresis donation more than 180 days prior [HR= 0.68 (0.50-0.93)]. CONCLUSION: Even mild adverse events reduce the return rates for a subsequent donation among platelet apheresis donors. Female donors, younger donors, and first-time donors are at higher risk of not returning after an immediate adverse reaction. Preventing the incidence of immediate adverse reactions during platelet apheresis donation may increase the rate of donor retention.

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI).

Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

Development and implementation of a COVID-19 convalescent plasma program in a middle-income economy.

Introduction: Convalescent Plasma therapy is one of the therapeutic strategies that has been used for patients with the Covid-19 disease. Implementing a program with national extension to supply hospitals with this blood component is a great challenge mainly in a middle-income economy. Objectives: Our objective was to develop and implement a Covid-19 Convalescent Plasma Program which met established quality standards and was adapted to a reality of limited resources. Methods: A multicentric convalescent plasma collection program was developed and implemented, based on four main sequential procedures: selective donor recruitment, pre-donation antibody screening (Anti-SARS-CoV-2- Chemiluminescence IgG Abbott), convalescent plasma collection by apheresis or whole-blood processing and distribution to the hospitals according to local demand. Results: From the 572 candidates submitted to the pre-donation antibody screening, only 270 (47%) were considered eligible for plasma donation according to the established criteria. Higher levels of total antibody were associated with the donor age being above 45 years old (p = 0.002), hospital admission (p = 0.018), and a shorter interval between the diagnosis of the SARS-CoV-2 infection and plasma donation (p < 0.001). There was no association between the ABO and Rh blood groups and their antibody levels. Of the 468 donations made, 61% were from the collection of whole-blood and 39%, from apheresis. The Covid-19 Convalescent Plasma units obtained were distributed to 21 different cities throughout the country by air or ground transportation. Conclusion: The implementation of a Covid-19 Convalescent Plasma program in a continental country with relatively scarce resources is feasible with alternative strategies to promote lower cost procedures, while complying with local regulations and meeting quality standards.

Association between FY*02N.01 and the severity of COVID-19: initial observations.

Introduction: The pro-inflammatory immune response underlies severe cases of COVID-19. Antigens of the Duffy blood group systems are receptors for pro-inflammation chemokines. The ACKR1 c.-67T>C gene variation silences the expression of Duffy antigens on erythrocytes and individuals presenting this variant in homozygosity have impaired inflammatory response control. Our aim was to evaluate the association between the ACKR1 c.-67T>C and the severity of COVID-19. Methods: This was a retrospective single-center case-control study, enrolling 164 participants who were divided into four groups: 1) Death: COVID-19 patients who died during hospitalization; 2) Hospital Discharge: COVID-19 patients who were discharged for home after hospitalizations; 3) Convalescent Plasma Donors: COVID-19 patients who were not hospitalized, and; 4) Controls: patients with diagnosis other than COVID-19. Patients were genotyped for the ACKR1 c.-67T>C (FY*02 N.01 allele) and the frequency of individuals presenting the altered allele was compared between the groups. Results: The groups significantly differed in terms of the percentage of patients presenting at least one FY*02N.01 allele: 36.8% (Death group), 37% (Hospital Discharge group), 16.1% (Convalescent Plasma group) and 16.2% (Control group) (p = 0.027). The self-declared race (p < 0.001) and the occurrence of in hospital death (p = 0.058) were independently associated with the presence of the FY*02N.01 allele. Hypertension (p < 0.001), age (p < 0.001) and the presence of at least one FY*02N.01 allele (p = 0.009) were independently associated with the need for hospitalization. Conclusion: There is a suggestive association between the presence of the FY*02N.01 and the severity of COVID-19. This may be a mechanism underlying the worse prognosis for Afro-descendants infected with SARS-CoV-2.