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 Medical Intensive Care Unit (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.
Subject(s)
COVID-19/immunology , Immunoglobulin G/immunology , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , Female , Humans , Immunoglobulin G/blood , Intensive Care Units , Length of Stay , Male , Middle Aged , Prognosis , Spike Glycoprotein, Coronavirus/immunologyABSTRACT
Off-label tocilizumab use in COVID-19 patients reflects concern for cytokine release syndrome. Comparison of matched COVID-19 pneumonia patients found elevated IL-6 levels correlated with mortality that did not change with tocilizumab administration. Correlating mortality with increased IL-6 doesn't imply causality however lack of improvement by tocilizumab requires further clinical trial alterations.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/immunology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , Ferritins/analysis , Humans , Interleukin-6/analysis , Male , Middle Aged , Odds Ratio , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Proportional Hazards Models , Receptors, Interleukin-6/immunology , SARS-CoV-2 , Survival RateABSTRACT
Off-label tocilizumab use in COVID-19 patients reflects concern for cytokine release syndrome. Comparison of matched COVID-19 pneumonia patients found elevated IL-6 levels correlated with mortality that did not change with tocilizumab administration. Correlating mortality with increased IL-6 doesn’t imply causality however lack of improvement by tocilizumab requires clinical trial alterations.