Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020

Hu, William T.; Howell, J. Christina; Öztürk, Tuğba; Benameur, Karima; Bassit, Leda; Ramonell, Richard P.; Cashman, Kevin S.; Pirmohammed, Shama; Roback, John D.; Marconi, Vincent C.; Yang, Irene; Mac, Valerie; Smith, Daniel; Sanz, Igñacio; Wharton, Whitney; Lee, F. Eun-Hyung; Schinazi, Raymond F.

doi:10.3201/eid2612.203334

Cited by 43 publications

(40 citation statements)

References 23 publications

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“…In contrast, anti-RBD IgG levels were not correlated with length of hospitalization (Figure 1b-e). Thus, these data indicate that elevated anti-S IgG levels are associated with worse disease outcome in severe COVID-19 patients, confirming previous observations that antibody responses were consistently higher among hospitalized subjects (Chen et al, 2020c; Chen et al, 2020d; Hu et al, 2020; Yu et al, 2020b). Notably, deceased patients did not have higher levels of virus-specific IgG or IgM than the live discharged patients (Fig.…”

Section: Mainsupporting

confidence: 89%

Kinetics of antibody responses dictate COVID-19 outcome

Lucas

Klein

Sundaram

et al. 2020

Preprint

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SummaryRecent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se, but rather with the delayed kinetics of NAb production.

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Section: Mainsupporting

confidence: 89%

Kinetics of antibody responses dictate COVID-19 outcome

Lucas

Klein

Sundaram

et al. 2020

Preprint

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“…Based on prior studies that described subjects with severe disease possessing a stronger and, perhaps, earlier humoral IgG response in both spike and nucleoprotein relative to subjects with mild disease 29,30 , we examined differences in epitope severity detected by SERA. We compared the SERA IgG panel score (developed to distinguish COVID-19 patients from pre-pandemic controls) across the spectrum of severities present in our population (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

High-resolution mapping and characterization of epitopes in COVID-19 patients

Haynes

Kamath

Bozekowski

et al. 2020

Preprint

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Fine scale delineation of epitopes recognized by the antibody response to SARS-CoV-2 infection will be critical to understanding disease heterogeneity and informing development of safe and effective vaccines and therapeutics. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify epitope binding specificities with single amino acid resolution. We applied SERA broadly, across human, viral and viral strain proteomes in multiple cohorts with a wide range of outcomes from SARS-CoV-2 infection. We identify dominant epitope motifs and profiles which effectively classify COVID-19, distinguish mild from severe disease, and relate to neutralization activity. We identify a repertoire of epitopes shared by SARS-CoV-2 and endemic human coronaviruses and determine that a region of amino acid sequence identity shared by the SARS-CoV-2 furin cleavage site and the host protein ENaC-alpha is a potential cross-reactive epitope. Finally, we observe decreased epitope signal for mutant strains which points to reduced antibody response to mutant SARS-CoV-2. Together, these findings indicate that SERA enables high resolution of antibody epitopes that can inform data-driven design and target selection for COVID-19 diagnostics, therapeutics and vaccines.

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“…There is evidence that those who are immunocompromised or asymptomatic may not seroconvert or only have a detectable antibody response for a short period of time [ 41 , 42 ]. Patients hospitalized due to COVID-19 with moderate or severe symptoms have shown a more pronounced and long-lived antibody response than those with mild or no symptoms [ 41 , 43 , 44 ]. Unlike commercial assay manufacturers that often rely on COVID-19 hospitalized patients with strict sample collection windows to determine the sensitivity and specificity of their assay, our study focused on a wide variety of participants of all ages with large variations in symptoms, outcomes and collection times.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Validation of Dried Blood Spot Sample Modifications to Two Commercially Available Covid-19 Igg Antibody Immunoassays

Zava

2020

Bioanalysis

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Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is labor-intensive, inconvenient and expensive compared with finger-stick capillary dried blood spot (DBS) collection. The purpose of our work was to determine if two commercially available anti-severe acute respiratory syndrome coronavirus 2 enzyme-linked immunosorbent assays for IgG antibodies against spike S1 subunit and nucleocapsid proteins could be validated for use with DBS. Materials & methods: Kit supplied reagents were used to extract DBS, and in-house DBS calibrators were included on every run. Results: Positive/negative concordance between DBS and serum was 100/99.3% for the spike S1 subunit assay and 100/98% for the nucleocapsid assay. Conclusion: Validation of the DBS Coronavirus disease 2019 IgG antibody assays demonstrated that serum and DBS can produce equivalent results with minimal kit modifications.

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Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020

Abstract: doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Cited by 43 publications

References 23 publications

Kinetics of antibody responses dictate COVID-19 outcome

Kinetics of antibody responses dictate COVID-19 outcome

High-resolution mapping and characterization of epitopes in COVID-19 patients

Validation of Dried Blood Spot Sample Modifications to Two Commercially Available Covid-19 Igg Antibody Immunoassays

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