Neutralizing activity to <scp>SARS‐CoV</scp>‐2 of convalescent and control plasma used in a randomized controlled trial

Freedenberg, Alex T.; Pan, Chun‐Hao; Diehl, William E.; Romeiser, Jamie; Hwang, Ga‐Ram; Leiton, Cindy V.; Muecksch, Frauke; Shroyer, Kenneth R.; Bennett‐Guerrero, Elliott

doi:10.1111/trf.16283

Cited by 9 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was on the basis of this that COVID-19 convalescent plasma administration started in many hospitals as the experimental treatment option; as passive antibody therapy [11]. According to the current recommendation, the convalescent plasma should have at least a 160 titer of the neutralizing antibodies, although titer 80 is still acceptable as a minimum threshold value [22]. To assess the ability of tested assays to predict the presence of neutralizing antibodies, we performed VNT and compared the results of titers with the values of SARS-CoV-2 antibodies measured by individual assays.…”

Section: Discussionmentioning

confidence: 99%

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Simanek¹,

Pecen²,

Krátká

et al. 2021

Diagnostics

View full text Add to dashboard Cite

There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient’s previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.

show abstract

Section: Discussionmentioning

confidence: 99%

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Simanek¹,

Pecen²,

Krátká

et al. 2021

Diagnostics

View full text Add to dashboard Cite

show abstract

“…Crucially, our group has recently confirmed the reliability of these nucleocapsid IgG antibody levels, with our data demonstrating a strong correlation between our prespecified IgG antibody to NP thresholds (145 and 300 reflectance units) and neutralizing antibody titers to the spike protein. 27 In this related study, all randomly selected convalescent plasma units with an nucleocapsid IgG level > 145 reflectance units exceeded the FDA's minimum 1:80 neutralizing antibody titer (Figure S1). 27 Our study was completed before the FDA raised concerns on June 16, 2020 regarding the suboptimal sensitivity and specificity of ChemBio DPP system for diagnosing COVID-19 infection (cutoff of 25 reflectance density units).…”

Section: Discussionmentioning

confidence: 95%

“…27 In this related study, all randomly selected convalescent plasma units with an nucleocapsid IgG level > 145 reflectance units exceeded the FDA's minimum 1:80 neutralizing antibody titer (Figure S1). 27 Our study was completed before the FDA raised concerns on June 16, 2020 regarding the suboptimal sensitivity and specificity of ChemBio DPP system for diagnosing COVID-19 infection (cutoff of 25 reflectance density units). These concerns were not relevant to our screening process, where we only selected donors who had very strong readings, that is, minimum of 145 and ideally over 300.…”

Section: Discussionmentioning

confidence: 95%

“…Importantly, our group has since demonstrated high neutralizing antibody titers to the spike protein in a random subset of samples obtained using these IgG NP antibody cutoffs (Figure S1). 27 We defined a priori four categories of screening IgG NP antibody levels: undetectable (<25), low/insufficient for donation (25-144), medium/adequate for donation (145-300), and high/adequate for donation (>300). 3.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Impact of serological and PCR testing requirements on the selection of COVID‐19 convalescent plasma donors

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID‐19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection. Study Design and Methods This prospective study was conducted at a tertiary care hospital in New York to select plasma donors for a randomized, double‐blind, controlled convalescent plasma trial. Clearance for donation required successful completion of an online questionnaire and an in‐person screening visit, which included (a) completion of a Donor Health Questionnaire (DHQ), (b) Immunoglobulin G (IgG) antibody testing using an immunochromatographic anti‐ severe acute respiratory coronavirus 2 (SARS‐CoV‐2) test, (c) Polymerase chain reaction (PCR) testing if <28 days from symptom resolution, and (d) routine blood bank testing. Results After receiving 3093 online questionnaires, 521 individuals presented for in‐person screening visits, with 40.1% (n = 209) fully qualifying. Subjects (n = 312) failed to progress due to the following reasons: disqualifying answer from DHQ (n = 30, 9.6%), insufficient antibodies (n = 198, 63.5%), persistent positive PCR tests (n = 14, 4.5%), and blood donation testing labs (n = 70, 22.4%). Importantly, 24.6% and 11.1% of potential donors who reported having PCR‐diagnosed infection had low or undetectable SARS‐CoV‐2 antibody levels, respectively. Surprisingly, 62.9% (56/89) of subjects had positive PCR tests 14–27 days after symptom resolution, with 13 individuals continuing to be PCR positive after 27 days. Conclusion It is feasible for a single site to fully qualify a large number of convalescent plasma donors in a short period of time. Among otherwise qualified convalescent plasma donors, we found high rates of low or undetectable antibody levels and many individuals with persistently positive PCR tests.

show abstract

“…The Spike (S) protein is a dominant immunoreactive protein and has several recognized regions, including the receptor binding domain [33][34][35][36][37][38][39]. Other recognized antigens commonly include Nucleocapsid (N), Membrane (M), orf3a, orf6, orf8, orf10, and Nsp5 (Mpro or 3CLpro) (Figure 1) [36,37,[39][40][41][42][43][44]. The latter may or may not include structural proteins of intact virus and may arise as proteins derived during the processes of infection.…”

Section: Immunogens and Humoral Immunitymentioning

confidence: 99%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

View full text Add to dashboard Cite

In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

show abstract

Neutralizing activity to SARS‐CoV‐2 of convalescent and control plasma used in a randomized controlled trial

Cited by 9 publications

References 23 publications

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Impact of serological and PCR testing requirements on the selection of COVID‐19 convalescent plasma donors

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Contact Info

Product

Resources

About