SARS-CoV-2 Omicron found to be more immune evasive than other variants among mild COVID-19 convalescent patients

By Pooja Toshniwal PahariaReviewed by Aimee MolineuxMay 19 2022

In a recent study published in Cell Reports Medicine, researchers evaluated the humoral and T lymphocyte immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) among mild coronavirus disease 2019 (COVID-19) convalescent patients in South Australia.

Background

Antibody responses and SARS-CoV-2 neutralization potential wane with time following SARS-CoV-2 infections and after vaccination with existing COVID-19 vaccines. SARS-CoV-2 VOCs possess several mutations in their spike (S) proteins which confer immune evasive properties to escape host immune responses. Therefore, the emergence of SARS-CoV-2 VOCs has increased the risk of convalescent patients and vaccine recipients to reinfections and has caused a hindrance in bringing the COVID-19 pandemic to an end.

About the study

In the present study, researchers assessed the humoral/antibody-mediated and T lymphocyte-mediated immunity among mild COVID-19 convalescents against SARS-CoV-2 VOCs after one year of infection with the ancestral (Wuhan-like) strain. The VOCs assessed were Alpha, Beta, Gamma, Delta, and Omicron.

The study cohort comprised 43 mild polymerase chain reaction (PCR)-confirmed COVID-19 convalescent patients.

Detailed assessments of immune responses against pseudotyped viruses, receptor-binding domain (RBD)-targeted B lymphocyte counts, and S- and non-S SARS-CoV-2 VOC-specific cluster of differentiation 4+ (CD4+) and CD8+ T lymphocyte immune responses, were undertaken. The neutralization of SARS-CoV-2 VOCs was assessed using neutralization assays. T lymphocytes were identified and quantified by activation-induced marker (AIM) assays using SARS-CoV-2 antigen peptide pools and flow cytometry analysis. The observations among the COVID-19 convalescents were compared to sex- and age-matched healthy individuals after six months and one year of infection.

In addition, the memory phenotype of SARS-CoV-2-specific CD4+ and CD8+ T lymphocytes was evaluated by measuring the expression of surface markers CD45RA and CCR7. Intracellular cytokine staining (ICS) of S-specific CD4+ and CD8+ T lymphocytes was performed to assess their functionality among the highly responding convalescents. Additionally. the frequency and functionality of -specific circulating T follicular helper cells (cT_FH) were assessed.

Results

Despite the ancestral RBD-targeted antibody and circulating memory B lymphocyte titers being conserved among most individuals, serum neutralization against live Omicron was completely abrogated and substantially decreased for the other SARS-CoV-2 VOCs.

Similarly, the ancestral strain-specific memory T lymphocyte frequencies were maintained in more than half of the COVID-19 convalescents but the lymphocytic cytokine response to Omicron and Beta S epitopes was impaired. The relative frequencies of CD4+ and CD8+ T lymphocytes did not differ between the two time points (six months and one year) and between COVID-19 convalescents and healthy individuals.

RBD-targeted serological immunoglobulin G (IgG) titers declined for all VOC isotypes after six months and one year of infection with the area under the curve (AUC) titers declining from 73-200 to 28-82, from 67-218 to 0.8-4, and from 0-44 to 0.2-0.9 for IgG, IgG1 and IgG3, respectively.  Above background levels of memory (CD27+) B lymphocytes expressing RBD-targeted IgG were observed among 89% of the convalescents (153 to 336 RBD-targeted lymphocytes/10⁶ B lymphocytes) in comparison to healthy individuals (28 RBD-targeted /10⁶ B lymphocytes). This was indicative of long-lasting (one year) humoral immune responses against SARS-CoV-2 among the COVID-19 convalescent patients.

After one year of infection, 64% and 44% of the serum samples of the COVID-19 convalescent patients yielded neutralization titers substantially above those of healthy controls against the ancestral S- and Alpha S-pseudotyped viruses. Neutralization titers for the live ancestral SARS-CoV-2 strain ranged between 16.8 and 40.8 with 51% of the convalescent patients demonstrating positive neutralizing activity.

Alpha neutralization titers ranged between 13 and 30. However, a remarkable decrease in live virus neutralization titers against Beta (0 to 2), Gamma (0.2 to 10), Delta (1.1 to 11), and Omicron (0.0 to 0.0) with only 5%, 12%, 16%, and 0% among the COVID-19 convalescents, respectively, demonstrating positive neutralization activity. This indicated that despite the increased prevalence of serum RBD-targeted antibodies, the existence of memory B lymphocytes, and SARS-CoV-2 neutralization by the COVID-19 convalescents, functional antibody-mediated/humoral immunity against SARS-CoV-2 VOCs substantially decreased one year after infection and were entirely abolished for Omicron.

In the phenotype analysis, between six months and 12 months of infection, the frequency of S-specific CD4+ T lymphocytes was substantially decreased in all memory compartments, central memory T lymphocytes (from 0.3-0.7 to 0.2-0.4), effector memory T lymphocytes (from 1-2 to 0.8-1.5) and terminal effector T lymphocytes (from 0.7-1.2 to 0.3-0.9). A similar trend was observed for memory subsets of non-S CD4+ T lymphocytes.

After one year of infection, the frequency of S-specific cT_FH among the mild COVID-19 convalescent patients and healthy individuals did not differ significantly. Likewise, the frequencies of c_TFH lymphocytes expressing cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and cytotoxic molecules such as granzyme B and perforins, were comparable among the two groups.

Conclusion

Overall, the study findings showed that Omicron was more immune evasive than other SARS-CoV-2 variants. The results highlighted the impairment in humoral and S-specific T lymphocyte immune responses post-infection among mild COVID-19 convalescent patients due to antigenic variability of the variants of concern.