Antibody Responses in COVID-19: A Review

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic. Although its seroprevalence is highly variable among territories, it has been reported at around 10%, but higher in health workers. Evidence regarding cross-neutralizing response between SARS-CoV and SARS-CoV-2 is still controversial. However, other previous coronaviruses may interfere with SARS-CoV-2 infection, since they are phylogenetically related and share the same target receptor. Further, the seroconversion of IgM and IgG occurs at around 12 days post onset of symptoms and most patients have neutralizing titers on days 14-20, with great titer variability. Neutralizing antibodies correlate positively with age, male sex, and severity of the disease. Moreover, the use of convalescent plasma has shown controversial results in terms of safety and efficacy, and due to the variable immune response among individuals, measuring antibody titers before transfusion is mostly required. Similarly, cellular immunity seems to be crucial in the resolution of the infection, as SARS-CoV-2-specific CD4+ and CD8+ T cells circulate to some extent in recovered patients. Of note, the duration of the antibody response has not been well established yet.

Keywords: COVID-19; SARS-CoV-2; antibodies; kinetics; neutralization; seroprevalence; therapeutics.

Figure 1

The flow diagram describes the process of literature review on antibody kinetics, neutralization, antibody-dependent enhancement, seroprevalence and convalescent plasma in COVID-19.

Figure 2

Seroprevalence in COVID-19. Subjects in green are uninfected people (neither current nor past) with negative serology; subjects in orange are infected people (current or past) with negative serology, and subjects in red are infected people (current or past) with positive serology. Estimating seroprevalence points to three primary conclusions. First, there appears to be a high variation among different territories worldwide. Second, although efforts to characterize the impact of SARS-CoV-2 are worth highlighting, there is still insufficient data to estimate the precise impact of this virus. Third, the studies on seroprevalence display the susceptibility of healthcare workers to SARS-CoV-2. However, the impact could be undermined due to individuals who become infected (COVID-19 positive) and have negative serological results.

Figure 3

Convalescent plasma. Plasma retrieved from convalescent COVID-19 patients displays both antiviral and immunomodulatory properties, including anti-inflammatory cytokines, complement blocking antibodies, auto-antibodies and anti-idiotype antibodies. However, evidence is so far contradictory, and the effectiveness of this treatment is unclear.

Figure 4

Antibody kinetics in COVID-19. The antibody kinetics show to be highly variable among individuals, but there seems to be a clear correspondence between severe disease, high antibody production and high neutralizing capacity, while the opposite is true with mild disease. Among the different studies, seroconversion appears at around 12 days. A characteristic finding is that there appears to be distinct kinetic profiles for the different antigens against which antibody responses are developed. The most important question which remains unsolved is whether antibody titers persist over time conferring protection, or if, on the contrary, antibody production wanes over time and renders people susceptible to reinfection.

Figure 5

Antibody neutralization in COVID-19. Three characteristics appear to hold a close relationship with high antibody neutralization capacity: male sex, old age and severe disease. A possible explanation is viral persistence in patients with these characteristics, but this is yet to be confirmed. On the other side of the spectrum, alternate mechanisms have been proposed for patients that do not develop robust neutralizing antibodies, such as high cytotoxic activity and a robust innate immune response, although these remain undetermined. For investigating neutralizing dynamics against SARS-CoV-2, other models with similar coronaviruses have been explored, such as SARS-CoV, MERS-CoV and endemic CoVs. Further investigation on neutralizing capacity will present definitive solutions to the enigmas of antibody-dependent enhancement, likelihood of reinfection and the effectiveness of treatments such as convalescent plasma.