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Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020

Our take —

This study aimed to characterize the immunological response to COVID-19 through IgM and IgG antibody profiles of participants with severe and mild diagnosed COVID-19 and a sample of individuals with self-limiting ILI in spring of 2020. This study included 103 pre-pandemic controls; 28 participants who were hospitalized for severe COVID-19; 15 participants who had recovered from mild COVID-19; and a community cohort of 116 persons who had recovered from self-limited influenza-like illness (ILI) during March and April 2020 in Atlanta, Georgia, USA. IgM reactivity toward S1 and E proteins increased early across COVID-19 severity levels, however IgG increased early only in hospitalized participants with severe COVID-19. The authors suggest that based on the delayed increase in IgG and neutralizing antibodies in individuals with mild COVID-19, that mild cases do not necessarily represent an intermediate stage between severe and asymptomatic COVID-19, but rather may be two distinct presentations of COVID-19.

Study design

Cross-Sectional

Study population and setting

This study measured IgM and IgG antibody profiles of participants with severe and mild confirmed COVID-19 as well as individuals with self-limiting influenza-like illness in the spring of 2020.Samples utilized in this study were collected from 103 individuals pre-2020 (controls); 28 participants who were hospitalized for severe COVID-19; 15 participants who had recovered from mild COVID-19; and a community cohort of 116 persons who had recovered from a self-limiting influenza like illness (ILI) not confirmed to be COVID-19 during March and April 2020 in Atlanta, Georgia, USA. This study used an IgG assay targeting the receptor-binding domain (RBD) of the spike protein subunit S1, an IgM assay targeting the full-length S1 protein, and an IgM assay targeting the small full-length envelope (E) protein. Samples were collected 15.5 days after symptom onset (median) among hospitalized participants and 15 days after symptom onset among participants who had recently recovered from mild COVID-19. The authors also examined neutralization of antibodies in a subset of samples.

Summary of Main Findings

Compared with control participants, hospitalized participants and participants with mild symptoms had higher levels of IgG against S1-RBD, IgM against S1, and IgM against E. The IgG diagnostic threshold of 0.82 optical density (OD) only identified 26.7% (4/15) of participants with mild illness, which may be due to the lower IgG levels early after symptom onset in the group with mild symptoms. Linear regression estimated that participants with mild illness would reach the OD threshold of hospitalized participants approximately 29 days after symptom onset. IgM negatively correlated with time since symptom onset for hospitalized participants. IgM reactive toward S1 and E proteins increased early in confirmed COVID-19 patient samples, regardless of disease severity. In contrast, IgG increased early only in hospitalized participants with severe COVID-19. Antibody neutralization was best associated with both positive IgG and IgM rather than each antibody independently.

Study Strengths

This study compares severe COVID-19 patients and mild COVID-19 patients to a control group of samples collected prior to 2020 to help understand the different IgM and IgG profiles among infected individuals based on disease severity.

Limitations

This study was cross-sectional and leveraged the time since symptom onset among patients to characterize the patterns of immunological response. However, this study in not able to assess the temporal patterns of IgM and IgG within individuals. This study has a small sample size and may be subject to selection bias. Linear regression was used to the OD threshold of hospitalized participants, however, may not be appropriate if antibody decline is not linear throughout the entire period. It remains to be seen how these antibody dynamics might relate to those among people with moderate COVID-19 disease or asymptomatic SARS-CoV-2 infection.

Value added

This study aims to aimed to better understand the dynamics of the serological response to SARS-CoV-2 infection in those with mild compared to severe COVID-19 disease.

This review was posted on: 8 June 2021