Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection

Atlanta, Georgia, USA, 2020

William T. Hu; J. Christina Howell; Tugba Ozturk; Karima Benameur; Leda C. Bassit; Richard Ramonell; Kevin S. Cashman; Shama Pirmohammed; John D. Roback; Vincent C. Marconi; Irene Yang; Valerie V. Mac; Daniel Smith; Ignacio Sanz; Whitney Wharton; F. Eun-Hyung Lee; Raymond F. Schinazi


Emerging Infectious Diseases. 2020;26(12):2974-2978. 

In This Article

Abstract and Introduction


Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.


Coronavirus disease (COVID-19) emerged in December 2019,[1,2] and by June 2020, ≈10 million persons worldwide had acquired the disease. The confirmatory test for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection remains real-time reverse transcription PCR, but this test poses challenges in terms of sensitivity,[3] reagent or equipment availability, and specialized personnel training. Serologic assays can be readily performed in most clinical laboratories, with faster turnaround times, but their association with COVID-19 has largely been reported for hospitalized patients with severe disease (;[4] E. Adams et al., unpub. data, Whether mild and severe COVID-19 represent 2 interlinked stages on a severity continuum or 2 distinct phenotypes of an infectious process[5] remains incompletely understood; detailed cross-sectional characterization of IgM and IgG reactive against SARS-CoV-2 antigens may provide insight into the temporal evolution of antibodies. Detection of cross-reactive antibodies from a pre-2020 cohort can also indicate whether past exposure to other coronaviruses is associated with cross-reactive protection against SARS-CoV-2.

In addition to IgG targeting the receptor-binding domain (RBD) of the spike protein subunit S1,[6] we developed and validated an IgM assay targeting the full-length S1 protein. We further developed and validated an IgM assay targeting the small full-length envelope (E) protein, which is highly shared between SARS-CoV and SARS-CoV-2,[2] is accessible on the surface, and increases during virus replication.[7] Using these assays, we characterized the IgM and IgG profiles of participants with COVID-19, pre-2020 control participants, and a community cohort of 116 persons who had recovered from self-limited illness during March and April 2020 in Atlanta, Georgia, USA.