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Front Immunol ; 12: 724763, 2021.
Article in English | MEDLINE | ID: covidwho-1399141


Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.

Antibodies, Viral/blood , Asymptomatic Infections , Immunoglobulin G/blood , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Structural Proteins/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/physiology , Binding Sites, Antibody , Female , Humans , Immunoglobulin G/classification , Immunoglobulin M/immunology , Kinetics , Male , Middle Aged , Neutralization Tests/statistics & numerical data , SARS-CoV-2/chemistry , Young Adult
JCI Insight ; 6(6)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1097059


Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.

Antibodies, Viral/physiology , CD4-Positive T-Lymphocytes/physiology , COVID-19/virology , Hospitalization , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus , Virion , Adult , Aged , Antibodies, Neutralizing/metabolism , Antibodies, Neutralizing/physiology , Antibodies, Viral/metabolism , CD4-Positive T-Lymphocytes/metabolism , COVID-19/epidemiology , COVID-19/immunology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/immunology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Female , Humans , Immunity, Humoral , Male , Middle Aged , Nucleocapsid , Severity of Illness Index , Viral Envelope , Viral Proteins , Young Adult
J Med Virol ; 93(5): 3158-3164, 2021 May.
Article in English | MEDLINE | ID: covidwho-1085668


Data regarding the immunological memory and long-time kinetics of immunoglobulin (IgG) against viral nucleoprotein (NP) and spike protein S1 receptor-binding domain (S1RBD) of Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2) are lacking. All consecutive COVID-19 patients admitted to our Clinic between March 1, 2020, and May 1, 2020, who were tested at hospital admission for anti-S1RBD and anti-NP IgG were enrolled. Serum samples were tested for anti-SARS-CoV-2 antibodies with the use of two commercially available enzyme-linked immunosorbent assays. Results are expressed as optical density measurements at 450 nm (OD450 ). Overall, 111 patients were included; the median (q1-q3) age was 57 (49-73) years, 59 (53%) males. According to disease severity, 31 (28%), 47 (42%), and 33 (30%) patients were considered affected by mild/moderate, severe, and critical SARS-CoV-2 infection, respectively. During hospitalization, patients with the critical disease showed a higher peak value of both anti-NP (median OD450 : 3.66 vs. 3.06 vs. 3.00 respectively, p = .043) and anti-S1RBD IgG (median OD450 : 2.33 vs. 1.6 vs. 0.91, respectively, p < .001). By testing 48 subjects 6 months or above from discharge, a significant decrease of anti-NP IgG was observed (r: -0.5838; p < .0001), whereas anti-S1RBD IgG showed only a modest reduction (r: -0.1507; p = .0647). Accordingly, 10 (21%) and 2 (4%) patients had a negative serological status for anti-NP and anti-S1RBD IgG, respectively; no association with clinical severity was found. IgGs against SARS-CoV-2 persisted several months after discharge, regardless of disease severity, suggesting that vaccination could be a valid strategy to fight the pandemic.

Antibodies, Viral/physiology , COVID-19/immunology , COVID-19/pathology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Aged , Female , Humans , Male , Middle Aged , Protein Binding , Protein Domains , SARS-CoV-2/metabolism