Tracking the evolution of anti-SARS-CoV-2 antibodies and long-term humoral immunity within 2 years after COVID-19 infection

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that gave rise to COVID-19 infection produced a worldwide health crisis. The virus can cause a serious or even fatal disease. Comprehending the complex immunological responses triggered by SARS-CoV-2 infection is essential for identifying pivotal elements that shape the course of the disease and its enduring effects on immunity. The span and potency of antibody responses provide valuable perspicuity into the resilience of post-infection immunity. The analysis of existing literature reveals a diverse controversy, confining varying data about the persistence of particular antibodies as well as the multifaceted factors that impact their development and titer, Within this study we aimed to understand the dynamics of anti-SARS-CoV-2 antibodies against nucleocapsid (anti-SARS-CoV-2 (N)) and spike (anti-SARS-CoV-2 (N)) proteins in long-term immunity in convalescent patients, as well as the factors influencing the production and kinetics of those antibodies. We collected 6115 serum samples from 1611 convalescent patients at different post-infection intervals up to 21 months Study showed that in the fourth month, the anti-SARS-CoV-2 (N) exhibited their peak mean value, demonstrating a 79% increase compared to the initial month. Over the subsequent eight months, the peak value experienced a modest decline, maintaining a relatively elevated level by the end of study. Conversely, anti-SARS-CoV-2 (S) exhibited a consistent increase at each three-month interval over the 15-month period, culminating in a statistically significant peak mean value at the study's conclusion. Our findings demonstrate evidence of sustained seropositivity rates for both anti-SARS-CoV-2 (N) and (S), as well as distinct dynamics in the long-term antibody responses, with anti-SARS-CoV-2 (N) levels displaying remarkable persistence and anti-SARS-CoV-2 (S) antibodies exhibiting a progressive incline.

Keywords: Anti-SARS-CoV-2 (N); Anti-SARS-CoV-2 (S); Kinetics; Long-term humoral immunity.

Figure 1

The scatter plot visually illustrates all observed samples, operating two y-axes with different measurement ranges. The experimental group axis, with a peak value of 300 U/ml, encompasses serum samples from 1661 patients. The control group axis has a peak value of 0.8 U/ml, representing the “pre-pandemic control group” including serum samples from healthy donors before and during the early phases of the SARS-CoV-2 pandemic. Values below 0.8 U/ml are considered negative, while those greater than or equal to 0.8 U/ml are deemed positive.

Figure 2

Seroprevalence of anti-SARS-CoV-2 (S) and (N). Figures (A) and (B) demonstrate anti-SARS-CoV-2 (S) and (N) antibodies of different convalescent patients with a 21-month follow-up and mean of each month. Figure C demonstrates the dynamics of anti-SARS-CoV-2 (S) and (N) within 21 months using two y-axes with different measurement ranges. The peak value for anti-SARS-CoV-2 (S) was 1000U/ml, for anti-SARS-CoV-2 (N)-140 COI.

Figure 3

Factors associated with anti-SARS-CoV-2 antibody production and kinetics. The statistical analysis was performed by a final adjusted multivariate logistic regression model (a, b) and linear mixed models (c) and data are exhibited with odds ratios (a) and p values (b, c) on the graphs. (A)—Female gender, Rh-negative blood type, and the severity of COVID-19 infection are associated with the anti-SARS-CoV-2 (N) and (S) production. Odds ratios are demonstrated in different colored dots to show the power of association for each factor ranged from 0–0.8. (B)—On the graph b the dots are represented p values to demonstrate the probability of the mentioned factors association with antibody production. The p values are coded with the following numbers: p < 0.001 = 4, 0.001–0.002 = 3, 0.002–0.01 = 2, 0.01–0.05 = 1, > 0.05 = 0. (C)—Graph c demonstrates the factors linked with the rate of reaching antibody peak and further decay rates. The p values are coded with the following numbers: p < 0.001 = 4, 0.001–0.002 = 3, 0.002–0.01 = 2, 0.01–0.05 = 1, > 0.05 = 0.

Figure 4

Violin plots for the distribution of antis-SARS-CoV-2 (S) & (N) for severity (A, B) and age (C, D) groups. Wider area of the violin plot represents a higher distribution of antibodies’ titer, and the thinner area corresponds to a lower distribution. Dots denote means for each month. Horizontal black dotted lines show the median of the antibodies’ titer and horizontal black dot lines represent the interquartile range (IQR) of the titer.