Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in “SAlpha”, “SBeta”, “SDelta”, and “SOmicron”, respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases

“…Several study studies reported that the elderly showed lower neutralization potency against the prototype and other VOCs (including B.1.1.7, B.1.351 and P.1.) than the younger individuals after one, two or three doses of vaccines ( Collier et al., 2021 ; Kawasuji et al., 2021 ; Liang et al., 2022 ; Newman et al., 2022 ; Tuekprakhon et al., 2022 ; Xu et al., 2021 ). The poor neutralizing responses, including lower levels of antibodies (quantity) and lower-affinity antibodies (quality), in the elderly individuals might be explained by reduced T-cell response ( Tober-Lau et al., 2021 ), lowered spike-specific IgG + IgM − CD19 + memory B cells, decreased somatic hypermutation in the BCR gene, or less enrichment for public BCR clonotypes associated with neutralization ( Collier et al., 2021 ).…”

“…The Omicron BA.4/5 variants have new mutations in their RBD, such as R493Q, L452R and F486V, indicating possible evolution from BA.2 ( Liang et al., 2022 ). In this study, BA.4/5 variants had 6.10-fold reduced neutralization in CLD patients and 5.11-fold in HCs when compared with the prototype, consistent with the result of a previous mRNA booster vaccination cohort ( Tuekprakhon et al., 2022 ).…”

COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old — — A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China

“…And after 40 years old, it shows a trend of sharp decline [35] . Besides, there was a study showed that in Omicron patients, young people had higher levels of neutralizing antibodies [36] . The above differences may allow the virus in young patients to be cleared faster without significantly affecting the immune system, so that the lymphocyte count is still within the normal range, and the clinical symptoms of young patients are relatively mild compared to the elderly [37] .…”

“…Moreover, specific anti-H1N1 virus drugs can quickly inhibit the virus, so that H1N1 virus can be quickly cleared in vivo. However, Omicron often has immune escape due to its strong mutation ability [45] , and the ability of neutralizing antibodies produced by the body to Omicron strain is significantly reduced [36] . Besides, the antiviral effect of Omicron is limited, which leads to a significant prolongation of virus clearance time.…”

Distinguishing COVID-19 from seasonal influenza in patients under age 65 years—a retrospective observational cohort study comparing the 2009 influenza A (H1N1) and 2022 SARS-CoV-2 pandemics

“…The diversity of T cells, which play an important role in viral elimination ( Kumar et al., 2018 ), gradually decreases and shows a sharp decline after age 40 years ( Simnica et al., 2019 ). One study showed that in patients with Omicron, younger people had higher levels of neutralizing antibodies ( Liang et al., 2022 ). These differences may allow faster and more efficient viral clearing in younger patients, without significantly affecting the immune system, so that their lymphocyte counts remain within the normal range; this is supported by evidence that clinical symptoms among younger patients are relatively mild compared with those of older adults ( Davies et al., 2020 ).…”