# Natural Infection of Omicron BA.5.2 in Patients Provides Broad Immune Responses Against SARS-CoV-2

**Authors:** Le Li, Tang Feng, Quan Shen, Xiaoshan Shi, Zhigong Wei, Wanze Chen, Fan Yang, Yueting Zhu, Chengxin Zhang, Shuang Zhang, Qisi Zhang, Shengwei Fu, Ning Wang, Wen-xia Tian, Jiyan Liu, Longlong Si

PMC · DOI: 10.3390/microorganisms13040746 · Microorganisms · 2025-03-26

## TL;DR

Natural infection with the Omicron BA.5.2 variant provides broad immune protection against various SARS-CoV-2 strains.

## Contribution

The study shows that natural infection with Omicron BA.5.2 induces broad and robust immune responses, including cross-reactive neutralization against multiple SARS-CoV-2 variants.

## Key findings

- Natural infection with BA.5.2 induces strong humoral and T cell-mediated immune responses.
- The immune responses are directed against conserved viral antigens and provide cross-reactive neutralization.
- Pre-vaccination reduces inflammation and severity of Omicron BA.5.2 infections.

## Abstract

The implementation of COVID-19 policy and the rapid development of SARS-CoV-2 vaccines in the early pandemic significantly contained numerous outbreaks and reduced the severity and mortality of COVID-19. However, the population immunity induced by existing vaccines was insufficient to prevent SARS-CoV-2 outbreaks. The host immunity induced by the wide spread of Omicron variants and its influence on emerging SARS-CoV-2 variants are attracting broad attention. In this study, a clinical data analysis of the patients indicated that pre-vaccination reduced inflammatory responses and mitigated the severity of COVID-19 cases caused by natural infection with Omicron BA.5.2. The analysis of adaptive immune responses indicated that natural infection with BA.5.2 induced robust and broad immune responses, including both humoral and T cell-mediated immune responses (IFN-γ) against highly conserved viral antigens, and provided cross-reactive neutralization against various viral variants. Collectively, we report that the natural infection with Omicron BA.5.2 induced broad cross-reactive immunity against SARS-CoV-2 variants, which suggests that the development of a live attenuated SARS-CoV-2 vaccine with desired safety, high efficacy, broad spectrum, and long-term immune persistence is feasible. Therefore, we suggest that herd immunity, achieved through vaccination with attenuated vaccines, combined with booster doses of existing vaccines and antiviral therapy for people with high viral loads, may contribute to the eradication of this virus.

## Linked entities

- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** COVID-19 (MESH:D000086382), inflammatory (MESH:D007249), Infection (MESH:D007239)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12029644/full.md

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Source: https://tomesphere.com/paper/PMC12029644