Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

doi:10.1016/j.ebiom.2023.104734

Observational Study

. 2023 Sep:95:104734.

doi: 10.1016/j.ebiom.2023.104734. Epub 2023 Jul 27.

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

Heba N Altarawneh¹, Hiam Chemaitelly², Houssein H Ayoub³, Patrick Tang⁴, Mohammad R Hasan⁴, Hadi M Yassine⁵, Hebah A Al-Khatib⁵, Asmaa A Al Thani⁵, Peter Coyle⁶, Zaina Al-Kanaani⁷, Einas Al-Kuwari⁷, Andrew Jeremijenko⁷, Anvar Hassan Kaleeckal⁷, Ali Nizar Latif⁷, Riyazuddin Mohammad Shaik⁷, Hanan F Abdul-Rahim⁸, Gheyath K Nasrallah⁵, Mohamed Ghaith Al-Kuwari⁹, Adeel A Butt¹⁰, Hamad Eid Al-Romaihi¹¹, Mohamed H Al-Thani¹¹, Abdullatif Al-Khal⁷, Roberto Bertollini¹¹, Laith J Abu-Raddad¹²

Affiliations

¹ Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address: hea2015@qatar-med.cornell.edu.
² Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
³ Mathematics Program, Department of Mathematics, Statistics, and Physics, College of Arts and Sciences, Qatar University, Doha, Qatar.
⁴ Department of Pathology, Sidra Medicine, Doha, Qatar.
⁵ Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
⁶ Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; Hamad Medical Corporation, Doha, Qatar; Wellcome-Wolfson Institute for Experimental Medicine, Queens University, Belfast, United Kingdom.
⁷ Hamad Medical Corporation, Doha, Qatar.
⁸ Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
⁹ Primary Health Care Corporation, Doha, Qatar.
¹⁰ Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA; Hamad Medical Corporation, Doha, Qatar; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
¹¹ Ministry of Public Health, Doha, Qatar.
¹² Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA; Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar. Electronic address: lja2002@qatar-med.cornell.edu.

PMID: 37515986
PMCID: PMC10404859
DOI: 10.1016/j.ebiom.2023.104734

Observational Study

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

Heba N Altarawneh et al. EBioMedicine. 2023 Sep.

. 2023 Sep:95:104734.

doi: 10.1016/j.ebiom.2023.104734. Epub 2023 Jul 27.

Authors

Affiliations

¹ Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address: hea2015@qatar-med.cornell.edu.
² Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
³ Mathematics Program, Department of Mathematics, Statistics, and Physics, College of Arts and Sciences, Qatar University, Doha, Qatar.
⁴ Department of Pathology, Sidra Medicine, Doha, Qatar.
⁵ Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
⁶ Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; Hamad Medical Corporation, Doha, Qatar; Wellcome-Wolfson Institute for Experimental Medicine, Queens University, Belfast, United Kingdom.
⁷ Hamad Medical Corporation, Doha, Qatar.
⁸ Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
⁹ Primary Health Care Corporation, Doha, Qatar.
¹⁰ Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA; Hamad Medical Corporation, Doha, Qatar; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
¹¹ Ministry of Public Health, Doha, Qatar.
¹² Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA; Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar. Electronic address: lja2002@qatar-med.cornell.edu.

PMID: 37515986
PMCID: PMC10404859
DOI: 10.1016/j.ebiom.2023.104734

Abstract

Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants.

Methods: Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests.

Findings: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently.

Interpretation: Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy.

Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Keywords: Booster; COVID-19; Case-control; Reinfection; Test-negative; Variant.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no competing interests.

Figures

**Fig. 1**
Effectiveness of previous pre-Omicron infection, vaccination with BNT162b2, and hybrid immunity of previous infection and vaccination against symptomatic Alpha, Beta, or Delta infections and against severe, critical, or fatal COVID-19 due to infection with these variants.

**Fig. 2**
Effectiveness of previous pre-Omicron infection, vaccination with mRNA-1273, and hybrid immunity of previous infection and vaccination against symptomatic Alpha, Beta, or Delta infections and against severe, critical, or fatal COVID-19 due to infection with these variants.

**Fig. 3**
Estimated effectiveness of hybrid immunity against symptomatic Alpha, Beta, Delta, BA.1 Omicron, BA.2 Omicron, and any Omicron infection compared to predicted effectiveness against these infections assuming independence of the effects of previous infection immunity and vaccination immunity (independence model prediction).

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References

1. Altarawneh H.N., Chemaitelly H., Hasan M.R., et al. Protection against the omicron variant from previous SARS-CoV-2 infection. N Engl J Med. 2022;386(13):1288–1290. - PMC - PubMed
1. Abu-Raddad L.J., Chemaitelly H., Coyle P., et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. eClinicalMedicine. 2021;35 - PMC - PubMed
1. Abu-Raddad L.J., Chemaitelly H., Ayoub H.H., et al. Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: a nationally representative cohort study. PLoS Med. 2021;18(12) - PMC - PubMed
1. Chemaitelly H., Bertollini R., Abu-Raddad L.J., National Study Group for Covid Epidemiology Efficacy of natural immunity against SARS-CoV-2 reinfection with the Beta variant. N Engl J Med. 2021;385(27):2585–2586. - PMC - PubMed
1. Chemaitelly H., Tang P., Hasan M.R., et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med. 2021;385(24):e83. - PMC - PubMed

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[1] Altarawneh H.N., Chemaitelly H., Hasan M.R., et al. Protection against the omicron variant from previous SARS-CoV-2 infection. N Engl J Med. 2022;386(13):1288–1290. - PMC - PubMed

[2] Altarawneh H.N., Chemaitelly H., Hasan M.R., et al. Protection against the omicron variant from previous SARS-CoV-2 infection. N Engl J Med. 2022;386(13):1288–1290. - PMC - PubMed

[3] Abu-Raddad L.J., Chemaitelly H., Coyle P., et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. eClinicalMedicine. 2021;35 - PMC - PubMed

[4] Abu-Raddad L.J., Chemaitelly H., Coyle P., et al. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. eClinicalMedicine. 2021;35 - PMC - PubMed

[5] Abu-Raddad L.J., Chemaitelly H., Ayoub H.H., et al. Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: a nationally representative cohort study. PLoS Med. 2021;18(12) - PMC - PubMed

[6] Abu-Raddad L.J., Chemaitelly H., Ayoub H.H., et al. Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: a nationally representative cohort study. PLoS Med. 2021;18(12) - PMC - PubMed

[7] Chemaitelly H., Bertollini R., Abu-Raddad L.J., National Study Group for Covid Epidemiology Efficacy of natural immunity against SARS-CoV-2 reinfection with the Beta variant. N Engl J Med. 2021;385(27):2585–2586. - PMC - PubMed

[8] Chemaitelly H., Bertollini R., Abu-Raddad L.J., National Study Group for Covid Epidemiology Efficacy of natural immunity against SARS-CoV-2 reinfection with the Beta variant. N Engl J Med. 2021;385(27):2585–2586. - PMC - PubMed

[9] Chemaitelly H., Tang P., Hasan M.R., et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med. 2021;385(24):e83. - PMC - PubMed

[10] Chemaitelly H., Tang P., Hasan M.R., et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med. 2021;385(24):e83. - PMC - PubMed

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Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

Affiliations

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

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