A longitudinal study of convalescent plasma (CCP) donors and correlation of ABO group, initial neutralizing antibodies (nAb), and body mass index (BMI) with nAb and anti-nucleocapsid (NP) SARS-CoV-2 antibody kinetics: Proposals for better quality of CCP collections.

INTRODUCTION: Little is known about the neutralizing (nAb) and binding antibody kinetics in COVID-19 convalescent plasma donors, especially during the first 100 days after disease onset. MATERIALS AND METHODS: A cohort of previously RT-PCR positive (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled in serial blood sample collection for a longitudinal nAb titers and anti-nucleocapsid (NP) antibodies (IgM, IgG and IgA) evaluation. NAbs were detected by a cytopathic effect-based virus neutralization test (CPE-based VNT), carried out with SARS-CoV-2 (GenBank: MT350282). RESULTS: A total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers ≥160 within 100 days after the onset of disease, there was >75% probability of sustaining nAb titers ≥160 in volunteers whose initial nAb titer was ≥1280, weight ≥ 90 kg or obese, according to their body mass index (BMI), as evidenced by Kaplan-Meier analysis and Cox hazard regression (all p < .02). There was no correlation between the ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti-NP (S/CO ≥5.0) is a good surrogate for detecting nAb ≥ 160, defined by the ROC curve (sensitivity = 90.5%; CI95%: 84.5%-94.7%). CONCLUSION: Selection of CCP donors for multiple collections based on initial high nAb titers (≥1280) or BMI ≥ 30 kg/m2 provides a simple strategy to achieve higher quality in CCP programs. High IgG anti-NP levels can also be used as surrogate markers for high nAb screening.

COVID-19 convalescent plasma cohort study: Evaluation of the association between both donor and recipient neutralizing antibody titers and patient outcomes.

BACKGROUND: Current evidence regarding COVID-19 convalescent plasma (CCP) transfusion practices is limited and heterogeneous. We aimed to determine the impact of the use of CCP transfusion in patients with previous circulating neutralizing antibodies (nAbs) in COVID-19. METHODS: Prospective cohort including 102 patients with COVID-19 transfused with ABO compatible CCP on days 0-2 after enrollment. Clinical status of patients was assessed using the adapted World Health Organization (WHO) ordinal scale on days 0, 5, and 14. The nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). The primary outcome was clinical improvement on day 14, defined as a reduction of at least two points on the adapted WHO ordinal scale. Secondary outcomes were the number of intensive care unit (ICU)-free days and the number of invasive mechanical ventilation-free days. RESULTS: Both nAbs of CCP units transfused (p < 0.001) and nAbs of patients before CCP transfusions (p = 0.028) were associated with clinical improvements by day 14. No significant associations between nAbs of patients or CCP units transfused were observed in the number of ICU or mechanical ventilation-free days. Administration of CCP units after 10 days of symptom onset resulted in a decrease in ICU-free days (p < 0.001) and mechanical ventilation-free days (p < 0.001). CONCLUSION: Transfusion of high titer nAbs CCP units may be a determinant in clinical strategies against COVID-19. We consider these data as useful parameters to guide future CCP transfusion practices.

Anti-A and SARS-CoV-2: an intriguing association.

BACKGROUND: Blood groups and anti-A isohemagglutinin may be involved in susceptibility to SARS-CoV-2 infection. MATERIALS AND METHODS: We retrospectively studied 268 COVID-19 convalescent plasma donors and 162 COVID-19 inpatients (total 430 subjects, confirmed by RT-PCR) and 2,212 healthy volunteer first-time blood donors as a control group. These were further divided into two groups: those with anti-A (blood types O and B) and those without it (types A and AB). Titres of nucleoproteins, and neutralizing SARS-CoV-2 antibody were measured in the convalescent plasma donors and inpatients. Multivariate logistic regression and non-parametric tests were applied. RESULTS: Persons having types O or B showed less infection prevalence than those of types A or AB (OR = 0·62, 95% CI 0·50-0·78; P < 0·001), but there was no difference when COVID-19 inpatients were analysed. Immunoglobulins M, G and A were lower in COVID-19 subjects of types O or B group than those of A or AB (0·16 vs. 0·19; P = 0·03, 2·11 vs. 2·55; P = 0·02, 0·23 vs. 0·32; P = 0·03, respectively). CONCLUSION: In this retrospective cohort, COVID-19 individuals were less likely to belong to blood types O and B, and also had lower SARS-CoV-2 antibody titres than A and AB individuals. COVID-19 severity did not associate with the blood groups.

Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: Preliminary lessons from a voluntary convalescent donor program.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. METHODS AND MATERIALS: Mild/moderate COVID-19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and absence of symptoms for ≥14 days plus (a) age (18-60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus-1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT-PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect-based virus neutralization test neutralizing antibody) and anti-nucleocapsid protein SARS-CoV-2 IgM, IgG, and IgA enzyme-linked immunosorbent assays. RESULTS: Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT-PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT-PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT-PCR -ve, and 25/69 RT-PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT-PCR -ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P < .05), probably denoting a "golden period" for CCP collection (≤28 days after joining the program); IgA might have an important role as neutralizing antibody. Donor's weight, days between disease onset and serial plasma collection, and IgG and IgM levels are important predictors for neutralizing antibody titer. CONCLUSIONS: RT-PCR +ve cases are still detected in 36.2% within 28 to 48 days after recovery. High anti-nucleocapsid protein IgG levels may be used as a surrogate marker to neutralizing antibody.

Novel FERMT3 and PTPRQ Mutations Associated with Leukocyte Adhesion Deficiency-III and Sensorineural Hearing Loss.

Leukocyte adhesion deficiency-III (LAD-III) is a rare genetic disease caused by defective integrin activation in hematopoietic cells due to mutations in the FERMT3 gene. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q and is essential for the normal maturation and function of hair bundle in the cochlea. Homozygous PTPRQ mutations impair the stereocilia in hair cells which lead to nonsyndromic sensorineural hearing loss (SNHL) with vestibular dysfunction. Here, we report two novel pathogenic homozygous mutations found in two genes, FERMT3 and PTPRQ , in a Brazilian patient with LAD-III and SNHL, which may develop our understanding of the phenotype-genotype correlation and prognosis of patients with these rare diseases.

Qualitative Study of Barriers and Facilitators to Care Among Children in Immigrant Families.

OBJECTIVES: Children in immigrant families comprise ∼25% of US children and live in families with high levels of poverty and food insecurity. Studies suggest a decline in public benefit enrollment among children in immigrant families. We aimed to explore perspectives on barriers and facilitators in accessing care among immigrant caregivers of hospitalized children. METHODS: With a general qualitative descriptive design, we developed a semistructured interview guide using an iterative process informed by literature and content expertise. Using purposive sampling, we recruited immigrant caregivers of hospitalized children in March 2020 and conducted interviews in English or Spanish. Interviews were recorded, transcribed, and translated to English. Three authors coded transcripts using Dedoose and identified themes via thematic analysis. RESULTS: Analysis of 12 caregiver interviews revealed barriers and facilitators in accessing healthcare and public benefit use. Barriers included healthcare system barriers, immigration-related fear, and racism and discrimination. Within healthcare system barriers, subthemes included language barriers, cost, complexity of resource application, and lack of guidance on available benefits. Within immigration-related fear, subthemes included fear of familial separation, fear of deportation, fear that benefit use affects immigration status, and provider distrust. Healthcare system facilitators of resource use included recruiting diverse workforces, utilizing language interpretation, guidance on benefit enrollment, legal services, and mental health services. Participants also recommended hospital partnership with trusted information sources, including media stations and low-cost clinics. CONCLUSIONS: Immigrant caregivers of hospitalized children identified barriers and facilitators in access to care. Further research is needed to assess the efficacy of caregiver-suggested interventions.

Hematopoietic stem cell transplantation in Puebla, México. Traveled roadand goals achieved

Introduction: In México there are only 4 cities that have significantly active hematopoietic stem cell transplantation programs; onlyin 3 of those cities, the most important national public health institution IMSS (Mexican Social Security Institute) count with them. The cities where these programs are found are Mexico City, Monterrey and Puebla. Since the beginning of this decade, and before, the productivity of these transplant programs in this public health institution is low, performing on average 148 transplants every year. Results: In the span comprised between April 1995 and October 2016, we have performed 474 hematopoietic transplants in our hospital; 229 of them were allogeneic and 245 autologous, in adult and children population. This accumulated experience has allowed the implementation of all the variety of hematopoietic stem cell transplantation available in our country, this has opened up the opportunity, for the first time in our institution, the possibility to provide a donor for every patient who requires an hematopoietic transplant, overcoming the phase in which patients could not be submitted to the procedure for lack of a compatible donor. Conclusions: The goals achieved in our hospital confirm the feasibility in developing uninterrupted long term transplant programs in hospitals not specially equipped with technology nor abundant funds of the public health system in the national province, and it shows that this programs can be created and developed in hospitals with similar conditions to ours in México, Latin America and middle-low income countries(AU)

Introducción: en méxico solo cuatro ciudades cuentan con programas de trasplante hematopoyético significativamente activos y en solo tres los tiene el IMSS, la principal institución de salud del país: Monterrey, Puebla y la ciudad de México .La productividad de estos centros del sector público es muy baja, realizando en conjunto 148 trasplantes en promedio por año desde el principio de la década actual. Resultados: en el lapso comprendido entre abril de 1995 y octubre de 2016, se efectuaron 474 trasplantes hematopoyéticos en nuestro hospital; 229 de ellos fueron alogénicos y 245 fueron autólogos, en población adulta e infantil. Esta experiencia acumulada ha permitido la implementación de todas las variedades disponibles en el país de estos procedimientos, lo que ha generado, por vez primera en la institución, poder contar con un donante para todo paciente que requiera un trasplante hematopoyético; superándose la etapa en la que los enfermos no se sometían al procedimiento por falta de un donador compatible. Conclusiones: la actividad acumulada en nuestra unidad hospitalaria confirma la factibilidad de desarrollar programas ininterrumpidos, a largo plazo, de estos procedimientos terapéuticos en hospitales no especialmente dotados de tecnología ni presupuesto del sector público de la provincia nacional y denota que estos mismos programas pueden ser creados y desarrollados en nosocomios con condiciones similares al nuestro en diversos territorios de México, de Latinoamérica y de países con ingreso medio-bajo(AU)