Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

Sen, Sanjana; Sanders, Emily; Gabriel, Kristin; Miller, Bill R.; Isoda, Hariny M.; Salcedo, Gabriela S.; Garrido, Jason E; Dyer, Rebekah P.; Nakajima, Rie; Jain, Aarti; Caldaruse, Ana-Maria; Santos, Alicia M; Bhuvan, Keertna; Tifrea, Delia F.; Ricks-Oddie, Joni; Felgner, Philip L.; Edwards, Robert A.; Majumdar, Sudipta; Weiss, Gregory A.

doi:10.1101/2020.10.15.341743

Cited by 5 publications

(12 citation statements)

References 56 publications

(53 reference statements)

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“…Plasma from healthy individuals provided an additional negative control. Confirming previously reported results, SARS-COV-2 Ep9 and a homologous epitope from SARS-CoV-1 (90% similarity) bound only to plasma from αEp9(+) patients 9 . The αEp9 Ab affinity for SARS-CoV-1 is unlikely to drive SARS-CoV-2 AIM due to the former’s limited spread in the US 12 .…”

Section: Resultssupporting

confidence: 90%

“…Commercially sourced plasma from healthy individuals provided an additional negative control. Confirming previously reported results, SARS-COV-2 Ep9 along with a homologous epitope from SARS-CoV-1 (90% similarity) bound only to plasma from αEp9(+) patients (Sen et al, 2021). Since only 75 cases of SARS-CoV-1 were reported in the US during the 2003 outbreak, this binding is unlikely to drive OAS (World Health Organization, 2013).…”

Section: Resultssupporting

confidence: 82%

“…Samples were collected as previously described (Sen et al, 2021). Briefly, the UC Irvine Experimental Tissue Resource (ETR) operates under a blanket IRB protocol (UCI #2012-8716) which enables sample collection in excess of requirements for clinical diagnosis, and allows distribution to investigators.…”

Section: Patient Sample Collectionmentioning

confidence: 99%

“…The patients, termed αEp9(+), comprised ≈27% of the sampled, SARS-CoV-2-infected population (n = 186). The αEp9(+) patients (n = 34) had high, early levels of αN IgGs, typically within the first week, compared to αEp9(-) patients; αEp9(+) individuals also experienced cytokine-related, immune hyperactivity 9 . These two observations suggest an AIM-based mechanism for the disease severity observed in αEp9(+) patients.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response

Sen

Sanders

Santos

et al. 2021

Preprint

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A previous report demonstrated the strong association between the presence of antibodies binding to an epitope region from SARS-CoV-2 nucleocapsid, termed Ep9, and COVID-19 disease severity. Patients with anti-Ep9 antibodies (Abs) had hallmarks of original antigenic sin (OAS), including early IgG upregulation and cytokine-associated injury. Thus, the immunological memory of a previous infection was hypothesized to drive formation of suboptimal anti-Ep9 Abs in severe COVID-19 infections. This study identifies a putative original antigen capable of stimulating production of cross-reactive, anti-Ep9 Abs. From bioinformatics analysis, 21 potential original epitope regions were identified. Binding assays with patient blood samples directly show cross-reactivity between Abs binding to Ep9 and only one homologous potential antigen, a sequence derived from the neuraminidase protein of H3N2 Influenza A virus. This cross-reactive binding affinity is highly virus strain specific and sensitive to even single amino acid changes in epitope sequence. The neuraminidase protein is not present in the influenza vaccine, and the anti-Ep9 Abs likely resulted from the widespread influenza infection in 2014. Therefore, OAS from a previous infection could underlie some cases of COVID-19 disease severity and explain the diversity observed in disease outcomes.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 82%

Section: Patient Sample Collectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response

Sen

Sanders

Santos

et al. 2021

Preprint

Self Cite

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“…The ability to simultaneously interrogate large numbers of putative targets, using low volumes of sample, significantly increases the rate at which antibody responses to antigens can be characterised. As such, protein microarray based approaches to biomarker identification and humoral response profiling in malaria, and other infectious diseases, have been increasingly adopted [15][16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum serology: A comparison of two protein production methods for analysis of antibody responses by protein microarray

Oulton

Obiero²,

Rodríguez

et al. 2020

Preprint

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The evaluation of protein antigens as putative serologic biomarkers of infection has increasingly shifted to high-throughput, multiplex approaches such as the protein microarray. In vitro Transcription/Translation (IVTT) systems (a similarly high-throughput protein expression method) are already widely utilised in the production of protein microarrays, though purified recombinant proteins derived from more traditional whole cell based expression systems also play an important role in biomarker characterisation. Here we have performed a side-by-side comparison of antigen-matched protein targets from an IVTT and purified recombinant system, on a protein microarray. The magnitude and range of antibody responses to purified recombinants was found to be greater than that of IVTT proteins, and responses between targets from opposing expression systems did not clearly correlate. However, responses between amino acid sequence-matched targets from each expression system were more closely correlated. Despite the lack of a clearly defined relationship between antigen-matched targets produced in each expression system, our data indicate that protein microarrays produced using either method can be used confidently, in a context dependent manner, though care should be taken when comparing data derived from contrasting approaches.

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Adaptive immune responses to SARS-CoV-2

Forthal

2021

Advanced Drug Delivery Reviews

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This review focuses on adaptive immune responses against SARS-CoV-2, the coronavirus that causes COVID-19. A great deal of work has been accomplished in a very short period of time to describe adaptive immune responses and to ascertain their roles in determining the course of infection. As with other viral infections, SARS-CoV-2 elicits both antibody and T-cell responses. Whereas antibody responses are likely effective in preventing infection and may participate in controlling infection once established, it is less clear whether or not they play a role in pathogenesis. T cells are likely involved in controlling established infection, but a pathogenic role is also possible. Longer term evaluation is necessary to determine the durability of protective immune responses.

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Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

Cited by 5 publications

References 56 publications

Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response

Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response

Plasmodium falciparum serology: A comparison of two protein production methods for analysis of antibody responses by protein microarray

Adaptive immune responses to SARS-CoV-2

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