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

PLoS One. 2021 Jun 10;16(6):e0252818. doi: 10.1371/journal.pone.0252818. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • C-Reactive Protein / analysis
  • C-Reactive Protein / immunology
  • COVID-19 / blood*
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • Female
  • Ferritins / blood
  • Ferritins / immunology
  • Hospitalization
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Inflammation / blood*
  • Inflammation / diagnosis
  • Inflammation / epidemiology
  • Inflammation / immunology
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-6
  • C-Reactive Protein
  • Ferritins

Grants and funding

This research was funded by Boston Heart Diagnostics, Framingham, MA, St. Francis Hospital, Trinity Health of New England, Hartford, Ct, Comite Center for Precision Medicine and Health, New York, NY, Atkinson Family Practice, Amherst, MA, Advanced Cardiology Institute, Fort Lee, NJ, and Diazyme Laboratories, Poway, CA. The authors were employees of Boston Heart Diagnostics (EJS, ML, ASG, MRD, LH, GB, MLD, LH, GB, MLD), Trinity Health of New New England (LD) Comite Center for Precision Medicine and Health (FC), Atkinson Family Practice (JJ), Grajower Medical Practice (MMG), Advanced Cardiology Institute (NEL), and Diazyme Laboratories (BS, CY). The funders provided support in the form of salaries for authors but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.