Immune response and severity of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants

Abstract

Introduction: COVID-19 continues to spread worldwide, with an increasing number of individuals experiencing reinfection after recovering from their primary infection. However, the nature and progression of this infection remain poorly understood. We aimed to investigate the immune response, severity and outcomes of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants.

Methods: We enrolled 432 COVID-19 cases who had experienced prior infection with the ancestral SARS-CoV-2 virus, Delta variant or Omicron BA.2 variant between January 2020 and May 2022 in Guangzhou, China. All cases underwent follow-up from March to April, 2023 through telephone questionnaires and clinical visits. Nasal lavage fluid and peripheral blood were collected to assess anti-RBD IgA, anti-RBD IgG and virus-specific IFN-γ secreting T cells.

Results: Our study shows that 73.1%, 56.7% and 12.5% of individuals with a prior infection of the ancestral virus, Delta or Omicron BA.2 variant experienced reinfection with the BA.5 variant, respectively. Fever, cough and sore throat were the most common symptoms of BA.5 reinfection, with most improving within one week and none progressing to a critical condition. Compared with individuals without reinfection, reinfected patients with a prior Delta infection exhibited elevated levels of nasal anti-RBD IgA, serum anti-RBD IgG and IFN-γ secreting T cells, whereas there was no noticeable change in reinfected individuals with a prior BA.2 infection.

Conclusion: These results suggest that BA.5 reinfection is common but severe outcomes are relatively rare. Reinfection with a novel SARS-CoV-2 variant different from the prior infection may induce a more robust immune protection, which should be taken into account during vaccine development.

Keywords: Omicron BA.5; SARS-COV-2 variants; disease severity; immune response; reinfection.

Figure 1

BA.5 reinfection rate and disease severity in individuals with primary infection with different variants. (A) Epidemic timeline of different primary infection and reinfection variants of SARS–CoV–2. (B) Incidence of BA.5 reinfection. Percentages were showed in the column. (C) Changes in clinical severity of BA.5 reinfection compared to primary infection. Case number were showed in the column.

Figure 2

Clinical symptoms of Omicron BA.5 reinfection. (A) Prevalence of symptoms reported in reinfection. (B) Duration of clinical symptoms in reinfection. (C, D) Prevalence and duration of symptoms during reinfection of the severe/critical cases in primary infection or cases older than 65. WT = wild type.

Figure 3

SARS–CoV–2 specific humoral and T cells response of participants with reinfection and non–reinfection. (A) Anti–RBD IgA antibody values in nasal lavage fluid. The RBD–IgA was detected by the semi–quantitative method which defines the result greater than 10 AU/ml as positive, bounded by the horizontal dotted line. (B) Anti–RBD IgG antibody values in serum. COI (cut off index) represents the ratio of the detected optical intensity value to the threshold value. If COI is less than 1, the result is negative. (C–E) Different T cellular response stimulated by three peptide pools. Numbers of IFN–γ–secreting cells per million PBMCs were shown. Statistical significance was determined using Mann–Whitney U–test. WT, wild type. RBD, receptor binding domain. NALF, nasal lavage fluid. PBMCs, peripheral blood mononuclear cells.