Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021–March, 2022: a national, observational, test...

Introduction

Adolescents have a lower risk of severe or fatal COVID-19 than adults.

¹

• Ladhani SN
• Amin-Chowdhury Z
• Davies HG
• et al.

COVID-19 in children: analysis of the first pandemic peak in England.

Consequently, in England and elsewhere, from December, 2020, the roll-out of COVID-19 vaccines prioritised older adults, health-care workers, and adults at high risk of severe disease. In young people, early reports of rare but potentially severe myocarditis following mRNA vaccination led the UK Joint Committee on Vaccination and Immunisation (JCVI) to recommend only one dose of mRNA vaccine for people aged 16–17 years from Aug 4, 2021, and recommend against vaccinating healthy people aged 12–15 years, as the margin of benefit was deemed too small to support universal vaccination in this age group.

²

Public Health England
JCVI issues updated advice on COVID-19 vaccination of young people aged 16 to 17.

^, 

³

Public Health England
JCVI issues updated advice on COVID-19 vaccination of children aged 12 to 15.

Ministers were, however, advised to seek guidance in evaluating the wider national context, which was outside the JCVI's remit. An expert group recommended universal vaccination of people aged 12–15 years, to prevent educational disruption, from Sept 13, 2021.

⁴

Public Health England
Universal vaccination of children and young people aged 12 to 15 years against COVID-19.

A second vaccine dose was subsequently recommended for both age groups, to be given at 8–12 weeks after the first dose, which is consistent with the UK recommendation for adult vaccination.

⁵

UK Health Security Agency
COVID-19 vaccination: a guide for eligible children and young people aged 12 to 17 (version 3).

By March 31, 2022, in England, 63·6% of people aged 16–17 years and 48·2% of people aged 12–15 years had received at least one COVID-19 mRNA vaccine dose, 42·9% and 25·7% had received at least two doses, and 6·3% and 0·2% had received three doses, respectively.

⁶

UK Health Security Agency
Coronavirus (COVID-19) in the UK.

Research in context

Evidence before this study

We searched PubMed and preprint servers SSRN and medRxiv on Sept 22, 2022, from Jan 1, 2020, to Sept 8, 2022, for papers in English, using the terms ("SARS-CoV-2" or "COVID-19") AND ("effectiveness" or "hybrid immunity" or "protection" or "waning" or "reinfection") AND ("delta" or "omicron") in the title or abstract. Most previous studies focused on adults and showed high protection from previous SARS-CoV-2 infection against reinfection with pre-omicron variants, but lower protection against reinfection with omicron (B.1.1.529) variants, with hybrid immunity providing the most robust protection. We have previously reported COVID-19 vaccine effectiveness in adolescents with no previous infection; however, there are limited data on the protection offered by infection with specific individual SARS-CoV-2 variants, and the added protection from vaccination, in adolescents with previous infection.

Added value of this study

Using national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England, we were able to estimate protection associated with previous SARS-CoV-2 infection, mRNA vaccination, and hybrid immunity from previous infection plus vaccination, using a test-negative, case-control design against PCR-confirmed symptomatic COVID-19. We found that protection against symptomatic infection with the delta (B.1.617.2) variant was greater than protection against symptomatic omicron infection in adolescents who had previous infection with wild-type, alpha (B.1.1.7), or delta variants. Similar trends were observed in vaccinated adolescents with no previous infection. Previous omicron infection together with vaccination provided the greatest protection against omicron variant infection.

Implications of all the available evidence

Previous SARS-CoV-2 infection with any variant provides some protection against reinfection, and COVID-19 mRNA vaccination also provides some protection. Our findings show, for the first time in adolescents, the additional protection afforded by hybrid immunity. In the context of the waves of omicron infections in the UK, our findings provide important evidence of only modest short-term protection against mild disease with omicron variant infection following vaccination, which has implications for the consideration of future adolescent COVID-19 vaccination and booster programmes.

There have been multiple waves of SARS-CoV-2 infections in the UK since March, 2020, with new waves often following the emergence and rapid spread of new variants, including the alpha (B.1.1.7) variant in November, 2020, delta (B.1.617.2) in April, 2021, and omicron (B.1.1.529) in November, 2021. Delta was more transmissible than alpha

⁷

• Kläser K
• Molteni E
• Graham M
• et al.

COVID-19 due to the B.1.617.2 (delta) variant compared to B.1.1.7 (alpha) variant of SARS-CoV-2: a prospective observational cohort study.

but, unlike in adults, it was not associated with more severe disease in children and adolescents.

⁸

• Delahoy MJ
• Ujamaa D
• Whitaker M
• et al.

Hospitalizations associated with COVID-19 among children and adolescents—COVID-NET, 14 states, March 1, 2020–August 14, 2021.

The ability of the omicron BA.1 variant, identified in England in late November, 2021, and the BA.2 variant, identified in late December, 2021, to evade both natural and vaccine-induced immunity was associated with the highest case numbers to date across all age groups, although hospitalisation rates and deaths remained low,

⁹

• Butt AA
• Dargham SR
• Tang P
• et al.

COVID-19 disease severity in persons infected with the omicron variant compared with the delta variant in Qatar.

which was likely to be due to immunity from a combination of previous infections and vaccination,

¹⁰

• Nyberg T
• Ferguson NM
• Nash SG
• et al.

Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.

and because the omicron variant infects the upper airway rather than the lower airway and causes less severe disease.

¹¹

• Peacock TP
• Brown JC
• Zhou J
• et al.

The altered entry pathway and antigenic distance of the SARS-CoV-2 omicron variant map to separate domains of spike protein.

^, 

¹²

• McMahan K
• Giffin V
• Tostanoski LH
• et al.

Reduced pathogenicity of the SARS-CoV-2 omicron variant in hamsters.

As in adults, we and others have shown a modest reduction in vaccine effectiveness over time against symptomatic delta disease in adolescents with no previous SARS-CoV-2 infection, and much lower vaccine effectiveness against symptomatic omicron disease, although protection against severe disease with both variants was higher after vaccination.

¹³

• Powell AA
• Kirsebom F
• Stowe J
• et al.

Effectiveness of BNT162b2 against COVID-19 in adolescents.

^, 

¹⁴

• Price AM
• Olson SM
• Newhams MM
• et al.

BNT162b2 protection against the omicron variant in children and adolescents.

Studies have shown that adults with hybrid immunity from a combination of previous infection and vaccination had greater, longer-lasting protection against reinfection than unvaccinated adults with previous infection or adults with no previous infection who had received two or more COVID-19 vaccine doses.

¹⁵

• Goldberg Y
• Mandel M
• Bar-On YM
• et al.

Protection and waning of natural and hybrid immunity to SARS-CoV-2.

^, 

¹⁶

• Altarawneh HN
• Chemaitelly H
• Ayoub HH
• et al.

Effects of previous infection and vaccination on symptomatic omicron infections.

Whether the same trends occur in adolescents, who are more likely than adults to remain asymptomatic or develop a mild illness when exposed to SARS-CoV-2, is not known.

¹

• Ladhani SN
• Amin-Chowdhury Z
• Davies HG
• et al.

COVID-19 in children: analysis of the first pandemic peak in England.

In England, SARS-CoV-2 PCR testing was freely available from June, 2020, to March, 2022. Given that around half of all adolescents have had at least one COVID-19 vaccine dose since September, 2021, together with high levels of community PCR testing, this provided a unique opportunity to assess protection against SARS-CoV-2 infection in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta and omicron BA.1 and BA.2 variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity.

Methods

Study design and participants

We conducted an observational, test-negative, case-control study in England. We estimated protection against PCR-confirmed COVID-19 (symptomatic SARS-CoV-2 infection) after combinations of previous infection with wildtype, alpha, delta, and omicron variants of SARS-CoV-2 with one or two BNT162b2 (Comirnaty, Pfizer-BioNTech) doses or a booster dose of either BNT162b2 or mRNA-1273 (Spikevax, Moderna), during periods of delta or omicron BA.1 and BA.2 dominance (appendix p 1). Symptomatic adolescents aged 12–17 years who were unvaccinated, or had received primary BNT162b2 immunisation, at symptom onset and had a community (Pillar 2) SARS-CoV-2 PCR test were included. Vaccination status and previous SARS-CoV-2 infection status in participants with PCR-confirmed COVID-19 (cases) were compared with vaccination status and previous infection status in participants who had a negative SARS-CoV-2 PCR test (controls).

PCR testing data for adolescents were extracted on May 31, 2022, for tests taken from Aug 9, 2021, when routine vaccination uptake in people aged 16–17 years started to increase, to March 31, 2022, when community SARS-CoV-2 PCR testing ended. We accessed the National Immunisation Management System (NIMS) on May 31, 2022, to collect dates of vaccination and vaccine manufacturer, sex, date of birth, race or ethnic group, and residential address. More details on data sources and linkage are provided in the appendix (p 2).

The UK Health Security Agency has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information under Section 3 for national surveillance of communicable diseases and, as such, individual informed consent was not required to access patient records.

Procedures

Previous infection was defined as PCR-confirmed SARS-CoV-2 infection at least 90 days before current sample date. Negative tests taken within 7 days of a previous negative test, and negative tests where the symptom onset date was within the 10 days of a symptom onset date for a previous negative test, were excluded as these were likely to represent the same episode. Negative tests taken within 21 days of a subsequent positive test were excluded as these were thought to possibly be false negative results. Positive and negative tests within 90 days of a previous positive test were excluded; however, where participants had later positive tests within 14 days of a positive test, then preference was given to PCR tests and tests associated with symptomatic infection. For adolescents who had more than one negative test, a maximum of two negative tests could be included per person, one from before Nov 22, 2021, and one after Nov 22 (before and after omicron emergence, respectively). Data were restricted to people who reported symptoms and gave a symptom onset date within the 10 days before testing to account for reduced PCR sensitivity beyond this period.

The variant responsible for each case was defined according to whole genome sequencing, genotyping, S-gene target failure (SGTF) status, or time period, with sequencing taking priority, followed by genotyping followed by SGTF status, as described previously.

¹⁷

• Andrews N
• Stowe J
• Kirsebom F
• et al.

Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England.

^, 

¹⁸

• Andrews N
• Stowe J
• Kirsebom F
• et al.

Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant.

Where subsequent positive tests within 14 days included sequencing, genotyping, or SGTF information, this information was also used to classify the variant. S target-negative status was used to define the omicron variant when it was responsible for at least 80% of S target-negative cases (from Nov 29, 2021, onwards). From Jan 10, 2022, delta cases were identified by sequencing and genotyping only because the positive predictive value of S target-negative status to identify the delta variant had decreased and could no longer be used. Tests were defined as delta where there was no SGTF, sequencing, or genotyping test done until Nov 28, 2021, (delta dominant period), and as omicron where there was no such test done from Jan 5, 2022 (omicron dominant period). Positive tests with no sequencing, genotyping, or SGTF between Nov 29, 2021, and Jan 4, 2022, were excluded as these could be omicron or delta (appendix p 3). Omicron included BA.1 and BA.2 subvariants, which were both circulating widely during the study period. We did not separate BA.1 and BA.2 in our analysis because both subvariants appeared in quick succession over a short time period (appendix p 3),

¹⁹

UK Health Security Agency
SARS-CoV-2 variants of concern and variants under investigation in England. Technical briefing 44.

and our previous analysis of real-world data showed similar vaccine effectiveness, and vaccine effectiveness rate of decline over time between the subvariants in adults.

²⁰

• Kirsebom FCM
• Andrews N
• Stowe J
• et al.

COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England.

The variant of previous infection was assigned only on the basis of the period when each variant was most common based on sequencing (see appendix p 2 for details on positive predictive values). Wildtype was assumed for the period before Dec 8, 2020, alpha for Dec 8, 2020–May 9, 2021, delta for May 10, 2021–Dec 12, 2021, and omicron from Dec 13, 2021, onwards. When considering previous infections, for participants with more than one previous positive test, the first positive test was used.

Statistical analysis

We performed logistic regression, with the PCR test result as the dependent variable and vaccination status as an independent variable. The primary outcome was protection against SARS-CoV-2 delta and omicron infection, defined as 1 – odds of vaccination or previous infection in cases divided by odds of vaccination or previous infection in controls, with vaccination stratified by time interval after each dose and previous variant infection. The protection from combinations of vaccination and previous infection was adjusted for in logistic regression models for age, sex, index of multiple deprivation quintile, ethnic group, geographical region (National Health Service region), period (calendar week of test), clinical risk group status (a separate flag for those aged 16 years or older and younger than 16 years), and clinically extremely vulnerable (if aged 16 years or older). Age was defined as age at Aug 31, 2021. Vaccination periods considered after each dose were 0–1 week, 2–14 weeks, 15–24 weeks, 25–39 weeks, and 40 or more weeks. CIs were obtained from the logistic regression models using the estimated log-odds ratio and it's SE. Once an individual received a second or third vaccine dose they no longer contributed to time after a previous dose. For booster vaccination, data for BNT162b2 and mRNA-1273 vaccinations were combined. Previous infection status was determined relative to 7 days after the first vaccination dose, with people who had infection before this period regarded as having infection before vaccination, and those who had infection during or after this period regarded as having infection after vaccination (irrespective of timing of other doses).

Role of the funding source

There was no funding source for this study.

Results

Between Aug 9, 2021, and March 31, 2022, 1 161 704 PCR tests were linked to NIMS data for COVID-19 vaccination status, including 390 467 positive tests with the delta variant and 212 433 positive tests with the omicron variant (table 1; appendix pp 3–5). There was a match rate of 93% of tests in adolescents that could be linked to NIMS, including 93% for both cases and controls and 92–93% by age in years. Overall, there were 558 804 negative tests, including 460 756 during the delta period and 225 447 during the omicron period. Some negative tests could be used as controls for both delta and omicron periods. 597 530 (51·4%) tests were in female participants and 562 279 (48·4%) were in male participants, and 927 923 (79·9%) were in White participants (table 1).

Table 1Characteristics of SARS-CoV-2 PCR test results among adolescents aged 12–17 years

Data are n (%).

In unvaccinated adolescents, protection against symptomatic delta infection was 87·6% (95% CI 86·8–88·4) after previous confirmed wildtype infection, 86·1% (85·4–86·8) after previous alpha infection, and 92·3% (91·7–92·9) after previous delta infection (table 2). Protection against symptomatic omicron infection was 32·7% (95% CI 27·7–37·4) after previous confirmed wildtype infection, 36·6% (32·9–40·1) after previous alpha infection, and 52·4% (50·9–53·8) after previous delta infection (table 2). Previous omicron infection was associated with protection of 59·3% (95% CI 46·7–69·0) against omicron reinfection, which was significantly lower than the protection associated with previous delta infection against delta reinfection.

Table 2Protection associated with previous infection by variant against symptomatic SARS-CoV-2 infection with the delta and omicron BA.1 and BA.2 variants in unvaccinated adolescents

Data are point estimate (95% CI).

Overall, mRNA vaccination protected against symptomatic delta infection in adolescents with no previous infection and provided additional protection in adolescents with previous infection. In adolescents with no previous infection, protection against delta after one vaccine dose was 59·4% (95% CI 58·8–60·0) after 2–14 weeks but decreased to 23·5% (18·3–28·3) after 15–24 weeks (table 3, figure 1). After two doses, protection against delta increased to 91·8% (91·2–92·3) after 2–14 weeks but was 71·9% (67·9–75·4) after 25–29 weeks. A third dose increased protection against delta to 96·0% (92·2–97·9) after 2–14 weeks; further follow-up was limited by the emergence of the omicron variant.

Table 3Protection from combinations of vaccination and previous infection with wildtype, alpha, and delta variants of SARS-CoV-2 against delta variant infection by time since vaccination

Data are point estimate (95% CI).

Figure 1Protection from combinations of vaccination and previous infection with wildtype, alpha, delta, and omicron variants BA.1 and BA.2 of SARS-CoV-2 against delta and omicron BA.1 and BA.2 infection, by time since vaccination

In adolescents with previous infection and at least one vaccine dose, protection against symptomatic delta infection was greater than 90% with limited waning over time after vaccination, irrespective of the infecting strain (wildtype, alpha, or delta) or whether the previous infection occurred before or after vaccination (table 3, figure 2).

Figure 2Protection from combinations of primary SARS-CoV-2 infection followed by vaccination or vaccination followed by primary SARS-CoV-2 infection with delta or omicron BA.1 and BA.2 variants against delta or omicron BA.1 and BA.2 reinfection, by time since vaccination

Overall, mRNA vaccination protected against symptomatic omicron infection in adolescents with no previous infection and provided additional protection in adolescents with previous infection, but to a lower extent than against delta (figure 1, table 4). In adolescents with no previous infection, protection against omicron was 18·8% (95% CI 17·2–20·3) at 2–14 weeks after vaccine dose one and peaked at 64·5% (63·6–65·4) at 2–14 weeks after dose two, before declining to 19·4% (11·7–26·4) by 25–39 weeks after dose two (figure 1, table 4). Protection increased to 62·9% (95% CI 60·5–65·1) at 2–14 weeks after dose three and then declined.

Table 4Protection from combinations of vaccination and previous infection with wildtype, alpha, delta, and omicron BA.1 and BA.2 variants of SARS-CoV-2 against omicron BA.1 and BA.2 variant infection by time since vaccination

Data are point estimate (95% CI).

Vaccination in adolescents who had previous infection with wildtype, alpha, delta, or omicron variants increased protection against symptomatic omicron infection, with higher peaks than in adolescents with no previous infection, reaching 85·3% (95% CI 83·7–86·8) with previous wildtype infection, 81·5% (80·0–82·9) with alpha, 78·8% (77·9–79·5) with delta, and 79·6% (44·9–92·4) with omicron, at 2–14 weeks after one vaccine dose (figure 1, table 4).

Protection against omicron infection waned after the first vaccine dose and then increased to 80–90% at 2–14 weeks after the second dose before waning again, to a greater extent in adolescents with previous wildtype infection (reaching a nadir of 53·4%, 95% CI 32·7–67·7), albeit with wide CIs, than in those with previous alpha infection (63·6%, 46·0–75·5) or previous delta infection (75·5%, 65·6–82·5), at 15–24 weeks after dose two (figure 1, table 4). A third vaccine dose boosted protection against omicron infection to 80–90% in adolescents who had previous infection with wildtype, alpha, or delta, but follow-up was limited to 2–14 weeks after dose three (table 4).

Similar trends in protection against symptomatic omicron infection were observed for adolescents who had previous infection with delta before vaccination compared with those who had previous delta infection after vaccination (figure 2, table 4).

There was short follow-up for adolescents vaccinated after previous omicron infection, with wide CIs because of small case numbers (figure 1, table 4). Adolescents who were vaccinated before primary omicron infection showed the highest protection against symptomatic omicron reinfection, with protection remaining high at 90·2% (95% CI 75·9–96·0) at 25–39 weeks after dose one and 96·4% (84·4–99·1) at 15–24 weeks after dose two (figure 2, table 4).

Discussion

There are limited data on the effects of natural and vaccine-induced immunity against SARS-CoV-2 in adolescents, with most reported studies focusing on adults. We found that primary SARS-CoV-2 infection with wildtype (estimated protection of 87·6%), alpha (86·1%), or delta (92·3%) was highly protective against subsequent symptomatic delta infection in unvaccinated adolescents, but less so against symptomatic omicron infection (32·7% with wildtype, 36·6% with alpha, and 52·4% with delta), while previous omicron infection provided an estimated protection of 59·3% against omicron reinfection. In adolescents with no previous infection, two mRNA vaccine doses provided an estimated protection of 92·3% against delta and although protection waned with time, high protection was restored after a third dose. By contrast, two doses provided lower protection (64·5%) against symptomatic omicron infection, with waning protection after each dose. In adolescents with previous infection, vaccination with one or two doses provided high protection against delta irrespective of the SARS-CoV-2 variant responsible for primary infection, which was sustained after each vaccine dose, with very little waning. Vaccination also added protection against symptomatic omicron infection in adolescents with previous infection, but with a lower peak and greater waning after each vaccine dose. High protection was observed against symptomatic omicron reinfection in vaccinated adolescents who had previous infection with omicron.

Our results support the findings of studies in adults that have shown high protection from previous infection against reinfection with pre-omicron variants.

¹⁵

• Goldberg Y
• Mandel M
• Bar-On YM
• et al.

Protection and waning of natural and hybrid immunity to SARS-CoV-2.

^, 

²¹

• Altarawneh HN
• Chemaitelly H
• Hasan MR
• et al.

Protection against the omicron variant from previous SARS-CoV-2 infection.

A study in Qatar reported that previous infection was associated with 90·2% protection (95% CI 81·9–94·6) against delta reinfection and 61·9% (48·2–72·0) against omicron in unvaccinated adults.

²¹

• Altarawneh HN
• Chemaitelly H
• Hasan MR
• et al.

Protection against the omicron variant from previous SARS-CoV-2 infection.

This is consistent with our data in unvaccinated adolescents showing lower protection against reinfection with omicron than with delta, which was likely to be because omicron variants harbour mutations that lead to evasion of natural and vaccine-induced immunity.

²²

• Cui Z
• Liu P
• Wang N
• et al.

Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 omicron.

Reassuringly, studies in adults have shown similar protection from mRNA vaccines against both BA.1 and BA.2 subvariants.

²⁰

• Kirsebom FCM
• Andrews N
• Stowe J
• et al.

COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England.

As previously shown in adults,

¹³

• Powell AA
• Kirsebom F
• Stowe J
• et al.

Effectiveness of BNT162b2 against COVID-19 in adolescents.

^, 

²³

• Andrews N
• Stowe J
• Kirsebom F
• et al.

Effectiveness of COVID-19 vaccines against the omicron (B.1.1.529) variant of concern.

we found limited, short-term protection from vaccination against symptomatic omicron infection, especially when compared with protection against delta in adolescents with no previous infection. We have previously reported higher protection in adolescents aged 12–15 years and those aged 16–17 years against symptomatic delta infection than against symptomatic omicron infection, including rapid waning in protection against symptomatic omicron infection after each vaccine dose in those aged 16–17 years.

¹³

• Powell AA
• Kirsebom F
• Stowe J
• et al.

Effectiveness of BNT162b2 against COVID-19 in adolescents.

In this study, we found that protection against symptomatic omicron infection wanes rapidly after each vaccine dose in adolescents with no previous infection and remained low at an estimated 33·6% even after three vaccine doses (at 15–24 weeks after vaccination). In a study in adults in Qatar, there was no protection against omicron BA.2 infection from 6 months after two BNT162b2 vaccine doses and 52·2% (95% CI 48·1–55·9) protection at 43 days after three doses.

¹⁶

• Altarawneh HN
• Chemaitelly H
• Ayoub HH
• et al.

Effects of previous infection and vaccination on symptomatic omicron infections.

Although timepoints are not directly comparable, consistent with data from the study in Qatar, we also observed a substantial reduction in protection against omicron infection to 19·4% at 25–39 weeks after dose two and 62·9% at 2–14 weeks after dose three.

Consistent with emerging literature in adults,

¹⁵

• Goldberg Y
• Mandel M
• Bar-On YM
• et al.

Protection and waning of natural and hybrid immunity to SARS-CoV-2.

^, 

¹⁶

• Altarawneh HN
• Chemaitelly H
• Ayoub HH
• et al.

Effects of previous infection and vaccination on symptomatic omicron infections.

^, 

²¹

• Altarawneh HN
• Chemaitelly H
• Hasan MR
• et al.

Protection against the omicron variant from previous SARS-CoV-2 infection.

and laboratory data in children and adolescents,

²⁴

• Dowell AC
• Lancaster T
• Bruton R
• et al.

Primary omicron infection elicits weak antibody response but robust cellular immunity in children.

we found that hybrid immunity provided the most robust protection against SARS-CoV-2 infection. In this study, protection against delta variant infection remained higher than 90% after previous infection with any pre-omicron variant and one or two BNT162b2 vaccine doses. Although vaccination improved protection against omicron in adolescents with previous infection, peak protection remained lower than against delta, with substantial waning over time after the first and second vaccine dose, although protection remained at 80–90% up to 3 months after the third dose. These data are consistent with the study in Qatar where a combination of previous infection and two BNT162b2 vaccine doses was associated with protection against BA.2 infection of 55·1% (95% CI 50·9–58·9) at a median of 270 days (IQR 213–296) between the second dose and PCR test, and a combination of previous infection and three BNT162b2 doses was associated with protection of 77·3% (95% CI 72·4–81·4) at a median of 43 days (IQR 26–65) between the third dose and PCR test.

¹⁶

• Altarawneh HN
• Chemaitelly H