SARS-CoV-2-Specific Antibody and T Cell Response Kinetics According to Symptom Severity

Abstract

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.

Figure 1.

Change of IgG and IgM antibody responses against the severe acute respiratory syndrome coronavirus 2 S1 protein in paired samples classified with symptom severities. The change of IgG and IgM antibody responses in the mild group at 1 week, 1 month, and 2 months after symptom onset in (A, D) the mild group, (B, E) the moderate group, and (C, F) the severe/critical group. OD = optical density. This figure appears in color at www.ajtmh.org.

Figure 2.

Change of interferon-γ-producing T-cell responses to severe acute respiratory syndrome coronavirus 2-specific overlapping peptides in paired samples classified with symptom severities. Spot-forming cells per 5 × 10⁵ peripheral blood mononuclear cells (PBMCs) stimulated with spike protein 1 (S1), spike protein 2 (S2), and nucleocapsid protein (N) at 1 week, 1 month, and 2 months after symptom onset in (A, D, and G), the mild group, (B, E, and H) the moderate group, and (C, F, and I), the severe/critical group. This figure appears in color at www.ajtmh.org.