Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes

Abstract

The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum of infected patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including MICU admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co)> 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio> 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection.

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

“…Previously, α N IgGs have been recognized as a focal site for an antibody response (18,19,21,36) and associated with disease severity and poor outcomes (11,36,37).…”

“…The S, N, and M proteins from SARS elicit an Ab-based immune response (8,9). The Ab response and its effects on disease progression in SARS-CoV-2 remain under investigation (10,11). Bioinformatics has predicted >55 Ab binding epitope regions from SARS-CoV-2 (12)(13)(14)(15)(16)(17).…”

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

“…The S, N, and M proteins from SARS elicit an Ab-based immune response ( 8 , 9 ). The Ab response and its effects on disease progression in SARS-CoV-2 remain under investigation ( 10 , 11 ). Bioinformatics has predicted >55 Ab binding epitope regions from SARS-CoV-2 ( 12 – 17 ).…”

Long-lasting humoral immunity in Covid-19 infected patients at a University Hospital Clinic in Östergötland County Council during 2020-2021

“…However, serum IgG/IgA against the NC-proteins have been described as both negative and positive for human health as described in different patient categories. In one study higher amounts of these immunoglobulins correlate with antibodydependent enhancement (ADE) of infection, even though no clear mechanistic process was presented (14), and in other studies these antibodies have been part of the cure/health promoting immune response. The possible positive interpretations or explanations given would be the clearance of circulating viral proteins that otherwise may cause formation of immune complexes, or result in inflammation at local sites where the NC-proteins aggregate (15).…”