Author
Ruchee Shrestha
Other affiliations: Johns Hopkins University
Bio: Ruchee Shrestha is an academic researcher from Johns Hopkins University School of Medicine. The author has contributed to research in topics: Medicine & Antibody. The author has an hindex of 8, co-authored 16 publications receiving 470 citations. Previous affiliations of Ruchee Shrestha include Johns Hopkins University.
Topics: Medicine, Antibody, Population, Immunology, Antiviral antibody
Papers
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TL;DR: Male sex, older age, and hospitalization with COVID-19 were associated with increased antibody responses across the serological assays, and IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population.
Abstract: Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers for S1, full-length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing antibody (nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed 95%-98% of the nAb-positive samples, but 20%-32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.
342 citations
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TL;DR: The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs) was evaluated.
Abstract: Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection (n=214) and pre-pandemic emergency department patients without SARS-CoV-2 infection (n=1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.
164 citations
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TL;DR: There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.
Abstract: Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32% Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays Neutralizing antibody titers were reduced over time in contrast to overall antibody responses There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels
139 citations
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TL;DR: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.
Abstract: BACKGROUND: Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. METHODS: SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (nâ
=â
16 individuals) and a cross-sectional sample of convalescent plasma donors (nâ
=â
130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. RESULTS: Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; Pâ
<â
.001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; Pâ
=â
.026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratioâ
=â
1.58 [95% confidence intervalâ
=â
1.19-2.12]), independent of age, sex, and hospitalization. CONCLUSIONS: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.
90 citations
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TL;DR: Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals, but did not necessarily have high diagnostic accuracy to detect high nabs.
Abstract: Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection for sensitivity (n=214) and pre-pandemic emergency department patients for specificity (n=1,102). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.
55 citations
Cited by
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French Institute of Health and Medical Research1, Rockefeller University2, University of Paris3, National Institutes of Health4, University of Tartu5, Lyon College6, Tartu University Hospital7, Utrecht University8, Vita-Salute San Raffaele University9, Yale University10, Pasteur Institute11, Collège de France12, University of Amsterdam13, McGill University Health Centre14, University of New South Wales15, Garvan Institute of Medical Research16, Ghent University Hospital17, University of Barcelona18, University of Vic19, Catalan Institution for Research and Advanced Studies20, Science for Life Laboratory21, Karolinska University Hospital22, Howard Hughes Medical Institute23, Aarhus University24, Aarhus University Hospital25, University of Milano-Bicocca26, University of Lorraine27, Haukeland University Hospital28, University of Bergen29, Karolinska Institutet30, Canadian Real Estate Association31, University of Brescia32, University of Pavia33
TL;DR: A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested.
Abstract: Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
1,913 citations
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TL;DR: In this article, the antibody response following the second dose of SARS-CoV2 mRNA vaccine in recipients of solid organ transplants was measured using a follow-up study.
Abstract: This follow-up study measures the antibody response following the second dose of SARS-CoV-2 mRNA vaccine in recipients of solid organ transplants.
745 citations
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TL;DR: It is hypothesized that age-related decline and dysregulation of immune function, i.e., immunosenescence and inflammaging play a major role in contributing to heightened vulnerability to severe COVID-19 outcomes in older adults and partitioning all immunological outcome data by age to better understand disease heterogeneity and aging.
495 citations
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TL;DR: In this article, the authors quantified antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals.
Abstract: This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals.
413 citations
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TL;DR: In this article, the authors evaluated the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19 and found no significant difference in 28-day mortality between the two groups.
383 citations