Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals

Markmann, Alena J.; Giallourou, Natasa; Bhowmik, Debaleena; Hou, Yixuan J.; Lerner, A. Martin; Martinez, David R.; Premkumar, Lakshmanane; Root, Heather; Duin, David van; Napravnik, Sonia; Graham, Stephen; Guerra, Quique; Raut, Rajendra; Petropoulos, Christos J.; Wrin, Terri; Cornaby, Caleb; Schmitz, John L.; Kuruc, JoAnn; Weiss, Susan R.; Park, Yara; Baric, Ralph S.; Silva, Aravinda M. de; Bartelt, Luther A.

doi:10.1128/msphere.00275-21

Cited by 42 publications

(55 citation statements)

References 57 publications

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“…In our 8-month follow-up, we also reported that 76% of the patients still had detectable Neutralizing Antibodies (NAb) (1). Many studies reported short-term follow-up observations of less than 6 months (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), whereas others reported longitudinal observations, typically spanning less than 12 months post symptom onset (1,4,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Some studies reported contraction of anti-COVID humoral responses with a stronger initial decline (1,4,(23)(24)(25)27).…”

Section: Introductionmentioning

confidence: 65%

“…An important aspect of monitoring humoral responses has been having access to plasma from the same patients over 14 months. Most reports were based on cross-sectional analysis spanning less than 6 months (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) or up to 12 months (1,4,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Depending on the patient cohort, several studies reported a stronger initial contraction (1,4,(23)(24)(25)27) of anti-COVID humoral responses.…”

Section: Discussionmentioning

confidence: 99%

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Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

2021

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Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a sequential evaluation of anti-SARS-CoV-2 antibodies in convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset. We report persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist better than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant, the prevalent strain of the present pandemic. These data show that convalescent patients maintain functional antibody responses for more than one year after infection, suggesting a strong long-lasting response after symptomatic disease that may offer a prolonged protection against re-infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months post-infection indicating SARS-CoV-2 re-exposure. These antibodies showed stronger cross-reactivity to a panel of Spike-RBD including Beta, Delta and Mu and neutralization of a panel of Spike variants including Beta and Gamma. This patient provides an example of strong anti-Spike recall immunity able to control infection at an asymptomatic level. Together, the antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity to the current variants of concern and show strong functional properties.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

2021

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“…This assay was shown to be 95.2% sensitive and 96.7% specific for detecting antibodies among individuals experiencing symptomatic infection at nine days since symptoms onset. 13 The spike RBD-based assay does not cross-react with common human endemic coronaviruses, and the magnitude of RDB antibody levels correlate with neutralizing antibody titers, currently the best correlate of protection against infection. In brief, ELISA plates (Greiner Bio-One #655061) were coated with 4µg/ml of the RBD antigen.…”

Section: Specimen Collection and Laboratory Methodsmentioning

confidence: 99%

“…A serum was considered seropositive if the absorbance of positive/negative ratio was ≥2.57, to ensure 99.5% specificity per CDC guidelines. 13,14…”

Section: Specimen Collection and Laboratory Methodsmentioning

confidence: 99%

“…We used a previously-validated in-house enzyme-linked immunosorbent (ELISA) assay to measure total antibodies (IgG, IgA and IgM) to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. This assay was shown to be 95.2% sensitive and 96.7% specific for detecting antibodies among individuals experiencing symptomatic infection at 9 days since symptoms onset [ 13 ]. The spike RBD-based assay does not cross-react with common human endemic coronaviruses, and the magnitude of RDB antibody levels correlates with neutralising antibody titres, currently the best correlate of protection against infection.…”

Section: Methodsmentioning

confidence: 99%

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Seroepidemiology of SARS-CoV-2 infections in an urban population-based cohort in León, Nicaragua

et al. 2021

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Analysis of 52 240 source plasma donors of convalescent COVID‐19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation

Schmidt¹,

Peter

Chastain³

et al. 2022

J of Clinical Apheresis

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Background COVID‐19 convalescent plasma (CCP) was approved under emergency authorization to treat critically ill patients with COVID‐19 in the United States in 2020. We explored the demographics of donors contributing plasma for a hyperimmune, plasma‐derived therapy to evaluate factors that may be associated with anti‐SARS‐CoV‐2 antibody response variability and, subsequently, antibody titers. Study Design An electronic search of CCP donors was performed across 282 US plasma donation centers. Donations were screened for nucleocapsid protein‐binding‐IgG using the Abbott SARS‐CoV‐2 IgG assay. Results Overall, 52 240 donors donated 418 046 units of CCP. Donors were of various ethnicities: 43% Caucasian, 34% Hispanic, 17% African American, 2% Native American, 1% Asian, and 3% other. Females had higher initial mean anti‐SARS‐CoV‐2 antibody titers but an overall faster rate of decline ( P < .0001). Initial antibody titers increased with age: individuals aged 55 to 66 years had elevated anti‐SARS‐CoV‐2 titers for longer periods compared with other ages ( P = .0004). African American donors had the lowest initial antibody titers but a slower rate of decline ( P < .0001), while Caucasian ( P = .0088) and Hispanic ( P = .0193) groups had the fastest rates of decline. Most donor antibody levels decreased below the inclusion criteria (≥1.50) within 30 to 100 days of first donation, but donation frequency did not appear to be associated with rate of decline. Conclusion Several factors may be associated with anti‐SARS‐CoV‐2 antibody response including donor age and sex. Evaluating these factors during development of future hyperimmune globulin products may help generation of therapies with optimal efficacy.

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Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals

Cited by 42 publications

References 57 publications

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

Seroepidemiology of SARS-CoV-2 infections in an urban population-based cohort in León, Nicaragua

Analysis of 52 240 source plasma donors of convalescent COVID‐19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation

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