SARS-CoV-2 antibody dynamics and B-cell memory response over time in COVID-19 convalescent subjects

Abstract

Objectives: The worldwide spread of coronavirus disease 2019 (COVID-19) highlights the need for assessment of long-term humoral immunity in convalescent subjects. Our objectives were to evaluate long-term IgG antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and B-cell memory response in COVID-19 convalescent subjects.

Methods: Blood samples were collected from a cohort of subjects recovering from COVID-19 and from healthy subjects who donated blood. SARS-CoV-2 IgG antibodies were quantitatively detected by ELISA using anti-S1 spike IgG. SARS-CoV-2 spike-specific IgG memory B cells were evaluated by reversed B-cell FluroSpot based on human IgG SARS-CoV-2 receptor-binding domain in a randomly selected group of subjects recovering from COVID-19. Statistical analysis was performed with clinical variables and time post COVID-19 infection.

Results: Antibody response was not detected in 26 of 392 COVID-19 convalescent subjects (6.6%). Over a period of 9 months, the level of antibodies decreased by 50% but stabilized at 6 months, and a protective level prevailed for up to 9 months. No differences were found regarding IgG SARS-CoV-2 antibody levels for age, gender, and major blood types over time. Over time, asymptomatic COVID-19 subjects did not differ in antibody level from subjects with mild to severe disease. Repeated paired IgG SARS-CoV-2 antibody level analyses disclosed that, over 6 and 9 months, 15.3% (nine of 59) and 15.8% (three of 19) of subjects became SARS-CoV-2 IgG-seronegative, respectively, all with a low antibody level at 3 months. Rate of antibody decline was not affected by age, gender, or clinical symptomatology. In a subgroup of recovering subjects, memory B-cell response up to 9 months post-COVID-19 infection was undetectable in 31.8% of subjects (14/44), and there was no correlation with age, SARS-CoV-2 antibody level, or time post infection.

Conclusions: The majority of convalescent COVID-19 subjects develop an IgG SARS-CoV-2 antibody response and a protective level prevails over a period of up to 9 months, regardless of age, gender, major blood types or clinical symptomatology.

Keywords: Anti-SARS-CoV-2 IgG; Antibody; COVID-19; Memory B-Cells; Time-related humoral response.

Fig. 1

Violin chart presentation (median and 25–75 IQR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels plotted against the time (months) since positive coronavirus disease 2019 (COVID-19) nasopharyngeal swab. (A) All subjects. Population stratified by: (B) age (>50 years, n = 70; ≤50 years, n = 318); (C) gender (females n = 108; males n = 284); and (D) clinical symptomatology (symptomatic, n = 358; asymptomatic, n = 34). The plots show the medians (middle line) and the first and third quartiles (boxes).

Fig. 2

Paired repeated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels over-time. (A) Paired SARS-CoV-2 IgG antibody levels plotted against the time (months) since positive nasopharyngeal swab in each subject. (B) SARS-CoV-2 IgG antibody levels plotted against the time (months) since positive coronavirus disease 2019 (COVID-19) nasopharyngeal swab in each subject. Red dots signify subjects who became seronegative.