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Clinical characteristics and immunogenicity after Omicron breakthrough infection in patients with chronic hepatitis B
Guanhua Zha1,2, Zhiwei Chen1,2, Na Wu1,2
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Insights
Omicron breakthrough infections in chronic hepatitis B patients caused mild COVID-19 without liver damage. These patients mounted strong antibody and T cell responses, similar to healthy controls.
Area of Science:
- Immunology
- Hepatology
- Infectious Diseases
Background:
- Clinical and immunological outcomes of breakthrough infections (BTI) in patients with chronic hepatitis B virus infection (CHB) during the Omicron wave remain unclear.
- Understanding these effects is crucial for managing CHB patients during ongoing viral outbreaks.
Purpose of the Study:
- To investigate the clinical and immunological features of patients with CHB following BTI during the Omicron wave.
- To compare immune responses in CHB patients with those in healthy controls (HCs) after BTI.
Main Methods:
- A cohort of 101 CHB patients and 39 HCs with BTI were followed.
- Clinical data were collected via questionnaires and electronic medical records.
- Antibody, B cell, and T cell responses were analyzed from blood samples.
Main Results:
- CHB patients experienced mild to moderate COVID-19 symptoms (median 5 days) after BTI.
- Liver function remained stable, and HBV-DNA was not activated.
- CHB patients showed robust antibody responses (NAbs 13.0-fold, BA.5 IgG 24.2-fold) and augmented CD4+, cTfh, and CD8+ T cell responses, comparable to HCs.
- Immune imprinting was observed in B cell responses but not T cell responses in CHB patients.
Conclusions:
- Omicron BTI in CHB patients results in mild COVID-19 without liver disease exacerbation.
- BTI effectively induces strong antibody and T cell immunity in CHB patients, comparable to healthy individuals.
Abstract:
The clinical and immunological features after breakthrough infection (BTI) during Omicron wave in patients with chronic hepatitis B virus infection (CHB) are still unclear. A total of 101 patients with CHB from our previous coronavirus disease 2019 (COVID-19) vaccination cohort (NCT05007665), were continued to be followed up at the Second Affiliated Hospital of Chongqing Medical University after BTI, while an additional 39 healthcare workers after BTI were recruited as healthy controls (HCs). Clinical data were collected using questionnaire survey and electronic medical record. Blood samples were used to determine the antibody responses, as well as B and T cell responses. After BTI, the clinical symptoms of COVID-19 were mild to moderate in patients with CHB, with a median duration of 5 days. Compared with HCs, patients with CHB were more susceptible to develop moderate COVID-19. The liver function was not significantly damaged, and HBV-DNA was not activated in patients with CHB after BTI. Patients with CHB could elicit robust antibody responses after BTI (NAbs 13.0-fold, BA.5 IgG: 24.2-fold, respectively), which was also significantly higher than that in every period after vaccination (all p < 0.001), and compared to that in HCs after BTI. The CD4+, cTfh, and CD8+ T cell responses were also augmented in patients with CHB after BTI, while exhibiting comparability to those observed in HCs. In patients with CHB after BTI, the immune imprint was observed in B cell responses, rather than in T cell responses. In conclusion, Omicron breakthrough infection induced mild to moderate COVID-19 symptoms in patients with CHB, without exacerbating the progress of liver diseases. Meanwhile, BTI demonstrated the ability to induce robust antibody and T cell responses in patients with CHB, which was comparable to those observed in HCs.
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