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

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.

Placental transfer dynamics and durability of maternal COVID-19 vaccine-induced antibodies in infants

“…Thus, the elevated IgG4 levels in infants whose mothers were vaccinated at < 20 weeks may be present due to increased passage of time and increased opportunity for antibody class switching in the mother, and these antibodies may have more muted effector functions and therefore may be less desirable to pass to infants than other subclasses of IgG. Consistent with this concept, we observed the highest levels of IgG3, the subclass most associated with an effective early anti-viral response 37 in infants whose mothers received the first vaccine dose after 20 weeks’ gestation.…”

“…Thus, the elevated IgG4 levels in infants whose mothers were vaccinated at < 20 weeks may be present due to increased passage of time and increased opportunity for antibody class switching in the mother, and these antibodies may have more muted effector functions and therefore may be less desirable to pass to infants than other subclasses of IgG. Consistent with this concept, we observed the highest levels of IgG3, the subclass most associated with an effective early anti-viral response 37 in infants whose mothers received the first vaccine dose after 20 weeks' gestation. Given the observed differences in infant antibody levels by timing of maternal vaccination, we next sought out to determine the combination of features that best separated infants based on timing of vaccination using partial least squares discriminant analysis (PLSDA), followed by least absolute shrinkage and selection operator (LASSO) feature regularization to prevent overfitting (Figure 3C).…”

Features of post-vaccination humoral immune response in the persons who underwent COVID-19 of various severity

“…Выявлена статистически значимая корреляция между тяжестью COVID-19 и концентрациями IgG-антител (как в целом, так и по подклассам). Показано, что уровни антител выше у пациентов с тяжелой клинической картиной [15]. Согласно другим данным, наличие анти-N и анти-RBD/S1 иммуноглобулинов не зависит от возраста, пола, групп крови, клинической симптоматики и тяжести перенесенного заболевания [17].…”

Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires

“…Subjects were labelled either "immunosuppressed" or "immunocompetent." Subjects were designated immunosuppressed if at least one of the following criteria was met: L the most recent CD4+ cell count was less than 100 cells/μl; L there was a diagnosis of lymphoma or leukemia associated with a healthcare encounter (visit, admission, or phone call) either before or within 60 days after sample collection; or L the subject was prescribed any of the following medications on an ongoing basis prior to sample collection and with enough refills to include up to 30…”

“…This is because NAbs are a marker of protection in SARS-CoV-2. [29][30][31] (T-cell-mediated immunity may also play an important role 32 ). And sixth, accessing clinical annotations from electronic medical records can be challenging.…”