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

Ernst J Schaefer,Maxine Lang,Latha Dulipsingh,Michael L Dansinger,Margaret R Diffenderfer,Jessica Jimison,Chong Yuan,Ben Saida,Gary Breton,Martin M Grajower,Andrew S Geller,Nathan E Lebowitz,Florence Comite,Lihong He,Pierre Roques

doi:10.1371/journal.pone.0252818

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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic
This type of research is exempted from requirement for human institutional review board (IRB) approval as per exemption 4, as listed at https://grants.nih.gov/policy/humansubjects. htm and at the open education resource (OER) website for research involving human subjects. This exemption “involves the collection or study of data or specimens if publicly available or recorded such that subjects cannot be identified”. We had this designation and our research reviewed by the Advarra Institutional Review Board (Columbia, MD)
Median high-sensitivity C reactive protein (hs-CRP) levels were very similar in control subjects and outpatients but were about 80-fold higher in inpatients as compared to other groups (P

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Up to 50% of SARS-CoV-2 positive patients can remain asymptomatic; such individuals can spread infections [7, 8]. The average onset of symptoms in symptomatic patients usually occurs within 5 days of exposure (range 2–14 days). Antibody testing has been reported to be useful for documenting exposure and potential immunity, as well as for case finding in family clusters and exposed individuals [9,10,11,12,13,14,15,16]. Treatment of symptomatic COVID-19 patients with convalescent plasma rich in antibodies or specific monoclonal antibodies may be useful in treating the disease [16,17,18,19,20,21]

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