urrogate test performance for SARS-CoV-2 neutralizing antibodies (nAbs) for convalescent plasma (CCP): How useful could they be

Author(s):Show less -

Wendel, Silvano ^[1] ; Fachini, Roberta ^[1] ; Fontao-Wendel, Rita C. L. ^[1] ; Mello, Ralyria ^[2] ; Velasquez, Carlos Vinicius ^[1] ; Guaragna Machado, Rafael Rahal ^[2] ; Brito, Mayra Altobelli ^[1] ; Amaral, Marcelo ^[1] ; Soares, Camila Pereira ^[2] ; Achkar, Ruth ^[1] ; Scuracchio, Patricia ^[1] ; Miyaji, Sandra Cristina ^[1] ; Erdens, Melina Santos ^[1] ; Durigon, Edison Luiz ^[2]

Affiliation

^[1] Hosp Sirio Libanes, Blood Bank, Rua Adma Jafet 91, BR-01308050 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo - Brazil

• Document type: Journal article
• Source: Transfusion; v. 61, n. 12 OCT 2021.
• Web of Science Citations: 0

Abstract

Background COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. Study design/methods We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers >= 160. Results Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers >= 160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb >= 160, including when using combined, orthogonal approaches. Conclusions Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection. (AU)

• FAPESP's process: 17/24769-2 - Zika virus in postpartum women and newborns: seroepidemiology and molecular characterization
• Grantee: Rafael Rahal Guaragna Machado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/06409-1 - Evaluation of humoral immune response and inflammatory response in patients with confirmed diagnosis of COVID-19 at Hospital Sírio Libanês and correlation with disease severity
• Grantee: Edison Luiz Durigon
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/20045-7 - Antigen discovery and development of serological diagnostic methods and vaccine approaches against the Zika Virus (ZIKV)
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/23680-0 - Standardization of Sherlock technique (Specific High-Sensitivity Enzymatic Reporter Unlocking) using the Cas13a protein for the diagnosis of respiratory syncytial virus in pediatric patients
• Grantee: Camila Pereira Soares
• Support Opportunities: Scholarships in Brazil - Master