SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma

Dulipsingh, Latha; Ibrahim, Danyal; Schaefer, Ernst J.; Crowell, Rebecca; Diffenderfer, Margaret R.; Williams, Kendra N.; Lima, Colleen; McKenzie, Jessica; Cook, Lisa D.; Puff, Jennifer; Onoroski, Mary; Wakefield, Dorothy; Eadie, Reginald; Kleiboeker, Steven B.; Nabors, Patricia; Hussain, Syed A.

doi:10.1016/j.transci.2020.102922

Cited by 29 publications

(16 citation statements)

References 28 publications

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“…This implies that the time from disease onset to antibody evaluation has an impact on the detected titers of anti-SARS-CoV-2 antibodies. This is consistent with previous studies showing that antibody levels decrease over time [9,16,19,27].…”

Section: Discussionsupporting

confidence: 93%

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Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

et al. 2020

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We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14–104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

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Section: Discussionsupporting

confidence: 93%

“…Moreover, we did not find any association between antibody production and blood type. This is also consistent with previous reports in the field [27]. Several studies have shown that blood type is not a prognostic factor for dismal outcomes among patients with symptomatic Covid-19 disease [32].…”

Section: Discussionsupporting

confidence: 93%

Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

et al. 2020

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“…The latter would be consistent with the variable antibody responses now determined for the spectrum of pediatric disease [44]. For EIA-based antibody studies otherwise, we have learned so far that the type and severity of disease and age may have bearing on the quality and quantity of antibody responses [34,[45][46][47][48]. Gender may also possibly affect antibody responses or other relevant immune responses [34,49].…”

Section: Provisional Acceptance Of What Constitutes Immunitysupporting

confidence: 64%

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Cimolai

2020

SN Compr. Clin. Med.

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Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy.

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“…Laboratories that only report a positive or negative value do not detect this large variability. Moreover, only about 50% of RNA positive outpatients had IgG levels >6.5 AU/mL, sufficient to provide estimated antibody titers of >1:320 as per FDA guidance, and only about one-third had plasma IgG levels >20 AU/mL, sufficient to provide estimated antibody titers >1:1000 [16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Antibody testing has been reported to be useful for documenting exposure and potential immunity, as well as for case finding in family clusters and exposed individuals [9][10][11][12][13][14][15]. Moreover, treatment of hospitalized COVID-19 patients with convalescent plasma rich in antibodies may be useful in treating the disease [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Clinical utility of Corona Virus Disease-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

Schaefer

Comite

Dulipsingh

et al. 2021

Preprint

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Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 (IL-6), C reactive protein (CRP), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive (≥1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if <45 years of age, 10.18 AU/mL if 45-64 years of age, and 10.85 AU/mL if ≥65 years of age (p<0.0001). In SARS-CoV-2 RNA positive cases, family members and exposed subjects (n=1,111), antibody testing was found to be valuable for case finding, and persistent IgM levels were associated with chronic symptoms. In non-hospitalized and hospitalized subjects assessed for SARS-CoV-2 RNA (n=278), median IgG levels in AU/mL were 0.05 in negative subjects (n=100), 14.83 in positive outpatients (n=129), and 30.61 in positive hospitalized patients (n=49, p<0.0001). Neutralizing antibody levels correlated significantly with IgG (r=0.875; p<0.0001). Two or more of the criteria of IL-6 ≥10 pg/mL, CRP ≥10 mg/L, and/or IgM >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p<0.0001). Our data indicate that: 1) IgG levels are significantly higher in positive older subjects, possibly to compensate for decreased cellular immunity with aging; 2) IgG levels are important for case finding in family clusters; 3) IgG levels are significantly correlated with neutralizing antibody levels; 4) persistently elevated IgM levels are associated with chronic disease; and 5) markedly elevated IL-6, hs-CRP, and/or positive IgM accurately identify SARS-CoV-2 RNA positive subjects requiring hospitalization.

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SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma

Cited by 29 publications

References 28 publications

Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

Anti–SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Clinical utility of Corona Virus Disease-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

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