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. 2022 Apr 29;14(5):941.
doi: 10.3390/v14050941.

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

Zoia R Korobova  1   2 , Elena V Zueva  1 , Natalia A Arsentieva  1 , Oleg K Batsunov  1   2 , Natalia E Liubimova  1 , Irina V Khamitova  1 , Raisa N Kuznetsova  1   2 , Artem A Rubinstein  2 , Tikhon V Savin  1   2 , Oksana V Stanevich  2 , Alexandr N Kulikov  2 , Dmitry E Pevtsov  2 , Areg A Totolian  1   2
Affiliations

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

Zoia R Korobova et al. Viruses. .

Abstract

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.

Keywords: COVID-19; IgG; IgG subclasses; severity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total anti-N protein antibody dynamics (quantitative ELISA) as a function of time since COVID-19 onset for 348 individual patients. The range was from 1 to 438 days. IgG concentration is presented in BAU/mL. The red dotted line represents the cut-off value for this specific ELISA kit (17 BAU/mL). The black line is the trend (r2 = 0.16).
Figure 2
Figure 2
Total anti-N protein IgG antibody dynamics (ELISA) by subclass, as a function of time since COVID-19 onset for 348 individual patients. The range was from 1 to 438 days. Concentration is presented in BAU/mL. The red line represents the cut-off value for this specific subclass. The black line is the trend, and R2 value is shown on each graph.
Figure 3
Figure 3
Differences in anti-N protein IgG subclass concentration depending on illness severity, Me (Q25–Q75).
Figure 4
Figure 4
Correlation matrix for anti-N protein IgG subclasses and illness severity, analyzed by Spearman correlation coefficient. Darker shades of green represent more solid correlation: 0.2–0.39—weak correlation; 0.4–0.69—fair correlation; 0.7–1.0—solid correlation. p-value for all presented coefficients < 0.0001.
Figure 5
Figure 5
Total anti-S protein (RBD) antibody dynamics (ELISA) as a function of time since COVID-19 onset for 312 individual patients. The range was from 1 to 438 days. IgG concentration is presented in BAU/mL. The red dotted line represents the cut-off value for this specific ELISA kit (22.6 BAU/mL). The black line is the trend, with an R2 of 0.28.
Figure 6
Figure 6
Total anti-S protein (RBD) IgG antibody dynamics (ELISA) by subclass, as a function of time since COVID-19 onset for 312 individual patients. The range was from 1 to 438 days. Concentration is presented in BAU/mL. The red line represents the cut-off value for this specific ELISA kit. The black line is the trend. R2 values are shown on the graph.
Figure 7
Figure 7
Differences in anti-S protein (RBD) IgG subclass concentration depending on illness severity, Me (Q25–Q75).
Figure 8
Figure 8
Correlation matrix for anti-S protein IgG subclasses and illness severity, analyzed with Spearman correlation coefficient. Darker shades of green represent more solid correlation: 0.2–0.39—weak correlation; 0.4–0.69—fair correlation; 0.7–1.0—solid correlation. p-value for all presented coefficients < 0.001.
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