Corona Virus Disease-19 serology, inflammatory markers, hospitalizations, case finding, and aging

Abstract

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.

Fig 1. Variability in SARS-CoV-2 IgG antibody response.

SARS-CoV-2 antibody response is shown in negative control subjects, for most of whom IgG values were <0.05 AU/mL and 100% were <1.0 AU/mL (dark blue circles); meat packing plant employees having antibody screening who were SARS-CoV-2 PCR RNA positive 2 weeks prior to testing (24.4% had IgG values <1.0 AU/mL) (orange circles); positive outpatients 4–6 weeks after positive SARS-CoV-2 RT-PCR RNA testing (3.9% had IgG values <1.0 AU/mL) (green circles); and positive SARS-CoV-2 RT-PCR RNA inpatients (6.1% had IgG values <1.0 AU/mL) (dark red circles). Dotted line indicates negative and positive SARS-CoV-2 IgG levels. IgG, immunoglobulin G; RT-PCR, reverse transcriptase-polymerase chain reaction.