Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients

Yang, He; Racine‐Brzostek, Sabrina; Karbaschi, Mohsen; Yee, Jim; Dillard, Alicia; Steel, Peter; Lee, William T.; McDonough, Kathleen A.; Qiu, Yuqing; Ketas, Thomas J.; Francomano, Erik; Klasse, P J; Hatem, Layla; Westblade, Lars F.; Wu, H.C.; Chen, Haode; Zuk, Robert; Tan, Hui; Girardin, Roxanne C.; Dupuis, Alan P.; Payne, Anne F.; Moore, John P.; Cushing, Melissa M.; Chadburn, Amy; Zhao, Zhen

doi:10.1016/j.bios.2021.113008

Cited by 23 publications

(29 citation statements)

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“…Monitoring individuals for antibody titers long term (as is done with the Hepatitis B or MMR vaccines), as well as monitoring neutralizing activity and avidity (23), may be prudent in determining the vaccine efficacy and the need for future booster vaccinations.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted August 5, 2021. ; https://doi.org/10.1101/2021.08.04.21261561 doi: medRxiv preprint HospNoVax demographics are summarized in Table 1 and further described in a previous validation study. (23) The median time from COVID-19 symptom onset to the ED visit was days (IQR 4-10). In an attempt to estimate time of infection for comparison studies with the vaccinated cohorts, it was estimated that the time of infection was 5 days prior to date of symptom onset.…”

Section: Non-vaccinated Cohorts (Retrospective)mentioning

confidence: 99%

“…Also of note, 39/122 (32%) were intubated, and 32/122 (26.2%) died during their hospitalization. (23) OutPtNoVax: 160 adult patients who had presented to an outpatient clinic in person or via video visit and had been tested for suspicion of prior COVID-19 infection. Specimen for SARS-CoV-2 serology testing occurred during the time period 4/30/2020 -5/20/2020.…”

Section: Non-vaccinated Cohorts (Retrospective)mentioning

confidence: 99%

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More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

Racine‐Brzostek

Yee

Sukhu

et al. 2021

Preprint

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Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaiveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaiveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ~6-months post-D1 (p=0.002). Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by ~6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Non-vaccinated Cohorts (Retrospective)mentioning

confidence: 99%

Section: Non-vaccinated Cohorts (Retrospective)mentioning

confidence: 99%

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More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

Racine‐Brzostek

Yee

Sukhu

et al. 2021

Preprint

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“…Anti-S antibody levels correlate well with those of neutralizing antibodies, including anti-RBD [30,33,38,48,62,64,81,86,88,90,106,[126][127][128][129][130][131][132]. Piccoli et al [50] have proposed that some 90% of neutralizing activity is due to anti-RBD antibody, and they have particularly mapped two dominant subepitopes.…”

Section: Correlations With Immunity or Protectionmentioning

confidence: 98%

“…A greater quantitation of antibody at the time of disease presentation may be associated with lesser mortality [30,90]. Others have found little difference of IgG reactivity to S protein among moderate to severe infections [88,91].…”

Section: Immunogens and Humoral Immunitymentioning

confidence: 99%

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

Cimolai¹

2021

CHI

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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.

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Association of Age With SARS-CoV-2 Antibody Response

et al. 2021

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IMPORTANCE Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults. OBJECTIVE To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years. MAIN OUTCOMES AND MEASURES SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years). RESULTS Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = −0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443

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Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients

Cited by 23 publications

References 32 publications

More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

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

Association of Age With SARS-CoV-2 Antibody Response

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