Immune evasion of SARS-CoV-2 omicron subvariants (B.1.1.529) resulted in large global waves of infection and raised concerns about vaccine efficacy against hospitalization and death related to COVID-19. In The Lancet Respiratory Medicine, Sara Y Tartof and colleagues1
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study. evaluated the effectiveness and duration of protection afforded by two doses and three doses of BNT162b2 (Pfizer–BioNTech) against hospital and ED admission after infection with omicron BA.1 or BA.2.1 subvariants
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study. Their study is timely, given the debate over the effectiveness of the current generation of COVID-19 vaccines against infection and disease in the age of omicrons.
One of the strengths of the study by Tartof and colleagues is that it was based on a large database containing the health records of more than 4.7 million patients from 15 hospitals in Southern California, USA . Data were retrieved from an integrated electronic platform with nearly complete information on comorbidities, PCR testing for COVID-19, and vaccination against COVID-19. The authors analyzed 16,994 adult hospital admissions for acute respiratory infection that occurred between December 27, 2021 and June 4, 2022 and involved RT-PCR COVID-19 testing. Using a test-negative design, Tartof and colleagues compared the vaccination status of 7435 admissions for BA.1 infection and 1056 admissions for BA.2 infection with that of 8503 admissions negative for SARS-CoV- 2. The median age of the study population was 55 years (IQR 36-73), 9823 (57.8%) of the 16,993 admitted were women and 7170 (42.2%) were men, and more than half of the admissions were people with a Charlson comorbidity index of 1 or more.
Tartof and colleagues found that the two-dose vaccination offered only partial and waning protection against hospital admission. Vaccine effectiveness against hospitalization was 54% (95% CI: 38 to 65) for BA.1 and 56% (-2 to 81) for BA.2 less than 6 months later of the second dose. Protection against BA.1-related hospitalization decreased to 32% (16 to 45) at 6 months or more after the second dose, but the decrease was not evident for BA.2. In contrast, three-dose vaccination induced high protection against hospital admission, with vaccine effectiveness equal to 80% (95% CI: 74 to 84) for BA.1 and 74% (47 at 87) for BA.2 less than 3 months later. the third dose. Booster protection was relatively durable: vaccine efficacy was 76% (69 to 82) against BA.1 and 70% (53 to 81) against BA.2 at 3 months or more after booster third dose Vaccine effectiveness against ED admission that did not require hospitalization was lower than against hospitalization and appeared to be substantially lower for BA.2 compared with BA.1.
Suboptimal vaccine protection against serious Omicron infections is of concern, but these estimates should probably be interpreted as minimum estimates of effectiveness. The authors defined the severity of COVID-19 by admissions related to acute respiratory infections with positive SARS-CoV-2 PCR test results. Massive pandemic waves BA.1 and BA.2 were associated with mild disease,2
- Ass AA
- Dargham MR
- Coyle P
- et al.
Severity of COVID-19 disease in individuals infected with omicron BA.1 and BA.2 sublineages and association with vaccination status. with many hospital or emergency room admissions related to acute respiratory infection with COVID-19 rather than due to COVID-19. Hospitalizations with incidental COVID-19 have become common in the omicron era and may lead to serious underestimations of vaccine protection against severe COVID-19.3.
- Stowe J
- Andrews N
- Kirsebom F
- Ramsay M
- Bernal JL
Effectiveness of COVID-19 vaccines against omicron and delta hospitalization: a study of cases and negative controls.4
- Feikin DR
- Abu-Raddad LJ
- Andrews N
- et al.
Evaluation of vaccine efficacy against severe disease of COVID-19 caused by the omicron variant. Report of a meeting of the World Health Organization. In Qatar4
- Feikin DR
- Abu-Raddad LJ
- Andrews N
- et al.
Evaluation of vaccine efficacy against severe disease of COVID-19 caused by the omicron variant. Report of a meeting of the World Health Organization. and the United Kingdom, 3
- Stowe J
- Andrews N
- Kirsebom F
- Ramsay M
- Bernal JL
Effectiveness of COVID-19 vaccines against omicron and delta hospitalization: a study of cases and negative controls. Specific definitions of severity of COVID-19 (ie, use of oxygen, mechanical ventilation, or admission to intensive care), as opposed to hospitalization alone, resulted in estimates of higher effectiveness and durability than those reported by Tartof and colleagues. Studies, including that of Tartof and colleagues, have also shown a gradient in vaccine efficacy against severe COVID-19, with higher and longer-lasting protection against more severe COVID-19.1 than less serious
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study.3
- Stowe J
- Andrews N
- Kirsebom F
- Ramsay M
- Bernal JL
Effectiveness of COVID-19 vaccines against omicron and delta hospitalization: a study of cases and negative controls.4
- Feikin DR
- Abu-Raddad LJ
- Andrews N
- et al.
Evaluation of vaccine efficacy against severe disease of COVID-19 caused by the omicron variant. Report of a meeting of the World Health Organization. This protection affirms the value of vaccination, despite immune evasion of omicron subvariants. To further explore this severity gradient and produce more representative estimates, studies should, whenever possible, use specific definitions of severe COVID-19, such as the WHO definitions for severe and critical COVID-19.In the context of other evidence about the effectiveness of the vaccine against COVID-19, Tartof and colleagues’ findings have important implications for the future shape of the pandemic. Strong and durable protection from the current generation of vaccines is increasingly looking like an elusive goal. Vaccine-derived immunity against infection with omicron subvariants declines rapidly over time.6
- Chemaitelly H
- Ayoub HH
- AlMukdad S
- et al.
Duration of mRNA vaccine protection against omicron BA.1 and BA.2 SARS-CoV-2 subvariants in Qatar. Viral evolution, leading to further immune evasion, will undermine vaccine protection and accelerate its decline.6
- Chemaitelly H
- Ayoub HH
- AlMukdad S
- et al.
Duration of mRNA vaccine protection against omicron BA.1 and BA.2 SARS-CoV-2 subvariants in Qatar. The same also applies to natural immunity induced by infection, although the decline in this context appears to be slower than that of vaccine immunity.7
- Chemaitelly H
- Nagelkerke N
- Job H
- et al.
Duration of immune protection from natural SARS-CoV-2 infection against reinfection in Qatar. These waning patterns suggest that the virus is likely to cause repeated temporal and geographic waves. The immune imprint could be another complication for the vaccine and natural immunity.8
- Reynolds CJ
- Pad C
- Gibbons JM
- et al.
Increased immunity by B.1.1.529 (omicron) depends on prior exposure to SARS-CoV-2.9
- Chemaitelly H
- Ayoub HH
- Tang P
- et al.
Immune protection against SARS-CoV-2 reinfection and immune imprinting. This pandemic is unlikely to end without considerable investment in the development of a new generation of vaccines that offer effective, long-term protection against a broad spectrum of potential variants. colleagues and other places,1
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study.10
- Abu-Raddad LJ
- Chemaitelly H
- Ayoub HH
- et al.
Effect of mRNA vaccine boosters against omicron SARS-CoV-2 infection in Qatar. remains the best intervention to reduce the severity of this pandemic. Boosters may need to be given at shorter intervals, at least to those who are clinically more vulnerable to severe COVID-19. Boosters restore vaccine protection to a high level for at least several months, even against immunoevasive omicron subvariants.1
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study.6
- Chemaitelly H
- Ayoub HH
- AlMukdad S
- et al.
Duration of mRNA vaccine protection against omicron BA.1 and BA.2 SARS-CoV-2 subvariants in Qatar.10
- Abu-Raddad LJ
- Chemaitelly H
- Ayoub HH
- et al.
Effect of mRNA vaccine boosters against omicron SARS-CoV-2 infection in Qatar. The new omicron-specific boosters should also offer greater and longer-lasting protection against currently circulating variants than boosters based on the original virus.
We declare no competing interests.
References
- 1.
- Tartof SY
- Slezak JM
- Puzniak L
- et al.
Efficacy and durability of BNT162b2 vaccine against hospital and ED admissions due to SARS-CoV-2 BA.1 and BA.2 omicron sublines in a large US health care system: a negative case-control study.
Lancet Respir Med. 2022; ()
- 2.
- Ass AA
- Dargham MR
- Coyle P
- et al.
Severity of COVID-19 disease in individuals infected with omicron BA.1 and BA.2 sublineages and association with vaccination status.
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