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Comparison of the Clinical Features, Viral Shedding and Immune Response in Vaccine Breakthrough Infection by the Omicron and Delta Variants

35 Pages Posted: 24 Jun 2022

See all articles by Sai Meng Tham

Sai Meng Tham

National University of Singapore (NUS) - National University Hospital

Siew‐Wai Fong

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Zi-Wei Chang

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Kai Sen Tan

National University of Singapore (NUS) - Department of Microbiology and Immunology

Angeline Rouers

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Yun Shan Goh

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Douglas Jie Wen Tay

National University of Singapore (NUS) - Department of Microbiology and Immunology

Sean Wei Xiang Ong

National Centre for Infectious Diseases, Singapore

Ying Hao

National Centre for Infectious Diseases

Siang Li Chua

National Centre for Infectious Diseases

Jean-Marc Chavatte

National Centre for Infectious Diseases

Lin Cui

National Centre for Infectious Diseases, Singapore

Matthew Zirui Tay

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Raymond Tzer Pin Lin

National Centre for Infectious Diseases

Laurent Renia

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Yee-Sin Leo

National University of Singapore (NUS) - Department of Microbiology and Immunology

Justin Jang Hann Chu

National University of Singapore (NUS) - Department of Microbiology and Immunology

David Chien Lye

Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine; National University of Singapore (NUS) - Department of Microbiology and Immunology

Lisa F.P. Ng

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Barnaby E. Young

National Centre for Infectious Diseases, Singapore

PROTECT Cohort Study Group

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

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Abstract

Background: On 26 November 2021, the World Health Organization designated the B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the fifth variant of concern, Omicron. Infections have quickly spread worldwide but understanding of the viral dynamics and the cytokine and cellular immunological response during infection remain limited. 

Methods: Detailed patient-level data from 174 age-matched patients with sequence confirmed Omicron or Delta infection (87 from each group) admitted to the National Centre for Infectious Diseases, Singapore were analysed in an observational cohort study. All patients had received a primary vaccination series against SARS-CoV-2. Peripheral blood samples for measurement of SARS-CoV-2 immunological parameters were obtained from a subset. Respiratory samples were collected for viral cultures and correlated to corresponding PCR cycle threshold (Ct) values. 

Results: Omicron and Delta variant infections in this hospitalized cohort were mild with only 3 (3/87; 3%) and 14 (14/87; 16%) developing pneumonia respectively. Omicron infections were more likely to present with sore throat (46·0 vs 23·0%, p=0·005). Neutrophil counts and C-reactive protein (CRP) were significantly lower among the Omicron cohort (Median neutrophil 2·95 [IQR 2·16 – 3·96] vs 4·60 [IQR 3·76 – 6·10] x 109/L, p<0·001; Median CRP 5·7 [IQR 2·0 – 10·0] vs 12·0 [IQR 6·1 – 22·0] mg/L, p<0·001).  Mean peak viral loads were significantly lower with Omicron infection (Ct 17·6 [IQR 16·3 – 19·3]) compared with Delta infection (Ct 14·9 [IQR 13·9 – 19·0]) (p=0·001). The pattern and rate of change in viral load based on Ct values was similar between Omicron and Delta. At the time of infection, vaccine breakthrough infections with the Omicron variant had a low concentration of proinflammatory cytokines, chemokines, and growth factors at the acute phase of infection, but a more robust IFN-γ response. Less dysregulated immune cell profiles were also observed, including a lower immature neutrophil cell count in Omicron breakthrough cases 

Conclusions: Omicron infections resulted in mild vaccine breakthrough illness in the majority of patients. Compared with Delta, Omicron infections were more frequently associated with upper respiratory tract infections, had lower viral loads, lower levels of pro-inflammatory cytokines and less dysregulated immune cell profiles.

Funding: This work was supported by the Biomedical Research Council (BMRC), A*CRUSE (Vaccine monitoring project), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001; COVID19RF-007; COVID19RF-0008; COVID19RF-060; OF-LCG19May-0034), Singapore National Medical Research Council Centre Grant Program – Diabetes, Tuberculosis and Neuroscience CGAug16M009 and A*STAR COVID-19 Research funding (H/20/04/g1/006).

Declaration of Interest: None to declare.

Ethical Approval: Waiver of informed consent for collection of clinical data from individuals infected with the Omicron variant was granted by the Ministry of Health (MOH), Singapore, under the Infectious Diseases Act as part of the COVID-19 outbreak investigation. Retrospective data collection from individuals with Delta infection was approved by the institutional ethics committee (REF: 2020/01122). Written informed consent was obtained from study participants for collection of biological samples after review (REF DSRB: 2012/00917).

Keywords: COVID-19, SARS-CoV-2, Delta, Omicron, variants of concern, vaccine breakthrough

Suggested Citation

Tham, Sai Meng and Fong, Siew‐Wai and Chang, Zi-Wei and Tan, Kai Sen and Rouers, Angeline and Goh, Yun Shan and Tay, Douglas Jie Wen and Ong, Sean Wei Xiang and Hao, Ying and Chua, Siang Li and Chavatte, Jean-Marc and Cui, Lin and Tay, Matthew Zirui and Lin, Raymond Tzer Pin and Renia, Laurent and Leo, Yee-Sin and Chu, Justin Jang Hann and Lye, David Chien and Ng, Lisa F.P. and Young, Barnaby E. and Cohort Study Group, PROTECT, Comparison of the Clinical Features, Viral Shedding and Immune Response in Vaccine Breakthrough Infection by the Omicron and Delta Variants. Available at SSRN: https://ssrn.com/abstract=4142078 or http://dx.doi.org/10.2139/ssrn.4142078

Sai Meng Tham (Contact Author)

National University of Singapore (NUS) - National University Hospital ( email )

Level 9
1E Kent Ridge Road
119228
Singapore

Siew‐Wai Fong

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Zi-Wei Chang

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Kai Sen Tan

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

Angeline Rouers

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs

Yun Shan Goh

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Douglas Jie Wen Tay

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

Sean Wei Xiang Ong

National Centre for Infectious Diseases, Singapore

Singapore

Ying Hao

National Centre for Infectious Diseases ( email )

Singapore

Siang Li Chua

National Centre for Infectious Diseases ( email )

Singapore

Jean-Marc Chavatte

National Centre for Infectious Diseases ( email )

Singapore

Lin Cui

National Centre for Infectious Diseases, Singapore ( email )

Singapore

Matthew Zirui Tay

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Raymond Tzer Pin Lin

National Centre for Infectious Diseases ( email )

Laurent Renia

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Yee-Sin Leo

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

5 Science Drive 2 Blk MD4, Level 3
117545
Singapore

Justin Jang Hann Chu

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

David Chien Lye

Nanyang Technological University (NTU) - Lee Kong Chian School of Medicine ( email )

National University of Singapore (NUS) - Department of Microbiology and Immunology ( email )

5 Science Drive 2 Blk MD4, Level 3
117545
Singapore

Lisa F.P. Ng

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs ( email )

Singapore

Barnaby E. Young

National Centre for Infectious Diseases, Singapore ( email )

Singapore

PROTECT Cohort Study Group

Agency for Science, Technology and Research (A*STAR) - A*STAR Infectious Diseases Labs