The latest SARS-CoV-2 variant of concern that emerged has been named omicron.
1
WHO
Classification of omicron (B.1.1.529): SARS-CoV-2 variant of concern. Declaration 26 November 2021.
Its immune evasion potential was predicted by genomic data and has so far been confirmed by observations of an increased incidence of reinfections and breakthrough infections.
2
- Pulliam JRC
- van Schalkwyk C
- Govender N
- et al.
Increased risk of SARS-CoV-2 re-infection associated with the emergence of the omicron variant in South Africa.
This has sparked calls for intensifying vaccination programs, including the delivery of vaccine boosters.
3
Omicron supercharges the debate over COVID vaccine boosters.
A group of German visitors who had received three doses of SARS-CoV-2 vaccines, including at least two doses of an mRNA vaccine, experienced breakthrough infections with omicron between late November and early December 2021 while in Cape Town, South Africa. The group consisted of five white women and two white men) with a mean age of 27 · 7 years (range 25–39) and an average body mass index of 22 · 2 kg / m2 (range 17 · 9–29 · 4)), without relevant medical history. Four of the individuals attended clinical optional training at various hospitals in Cape Town while the others were on vacation. The persons were members of two unaffiliated social groups and participated in the ordinary social life of Cape Town in accordance with the applicable COVID-19 protocols. Upon arrival during the first half of November 2021, each individual tested negative for SARS-CoV-2 by PCR and provided records of complete vaccination, including booster or third doses administered via intramuscular injection using homolog (n = 5) and heterologous (n = 5) n = 2) vaccination course (Appendix s 3).
4
European Medicines Agency
EMA and ECDC recommendations on heterologous vaccination courses against COVID-19.
Six individuals were fully vaccinated with BNT162b2 (Comirnaty, Pfizer – BioNTech, Mainz, Germany), five of whom received a third (booster) dose of BNT162b2 in October or early November 2021. One individual had received a full dose of CX-024414 (Spikevax, Moderna, Cambridge, MA, USA) in early October 2021; this was not in line with the recommendations of the European Medicines Agency at the time, which suggested a half dose to boost healthy individuals.
5
European Medicines Agency
Spikevax: EMA booster recommendation.
The seventh individual received an initial dose of ChAdOx1-S (Vaxzevria, AstraZeneca, Cambridge, UK), followed by a dose of BNT162b2 to complete primary immunization and a booster dose of the same vaccine. Except for the CX-024414 booster, all vaccinations were in accordance with European recommendations.
4
European Medicines Agency
EMA and ECDC recommendations on heterologous vaccination courses against COVID-19.
,
5
European Medicines Agency
Spikevax: EMA booster recommendation.
The early days of some individuals’ primary and booster vaccinations were due to their profession in the medical field. No one reported a history of SARS-CoV-2 infection.
During a marked increase in the incidence of SARS-CoV-2 infections in the Western Cape province, these individuals observed incipient respiratory symptoms between November 30 and December 2, 2021. SARS-CoV-2 infections were diagnosed by ISO 15189-accredited diagnostic laboratories using molecular analyzes approved by the national regulator.
The study was approved by the Health Research Ethics Committees at Stellenbosch University (C21 / 12 / 004_COVID-19) and the University of Cape Town (279/2021), and all participants gave informed consent.
We received inoculation and serum samples 2-4 days after the onset of symptoms. Further details on how the samples were treated can be found in the appendix (p. 2). All patients were placed in domestic isolation and used a daily symptom diary to document the course of the disease during the 21-day observation period.
Disease was classified as mild (n = 4) or moderate (n = 3; shortness of breath) according to the National Institutes of Health COVID-19 Treatment Guidelines. Two subjects were asymptomatic at the end of the observation period (day 21). Blood oxygenation levels (SPO)2) remained in the normal range (> 94%) without exception and none of the patients required hospitalization. Occurrence of symptoms over time is indicated in the appendix (p. 4).
All seven individuals were infected with omicron (PANGO pedigree B.1.1.529, Nextstrain clade 21K). Viral load ranged from 4 · 07 to 8 · 22 (average 6 · 38) log10 viral RNA copy pr. ml swab eluate. Anti-spike antibody levels ranged from 15,000 random units (AU) per ml to more than 40,000 AU / mL, with an average of approx. 22,000 AU / mL serum (Appendix p. 3).
Robust CD4 and CD8-T cell responses to SARS-CoV-2 tip, nucleocapsid, and membrane proteins were detected in six of the participants tested at least 2 weeks after symptom onset (Appendix p. 5), with frequencies of 0 · 011 –0 · 192% for CD4 + and 0 · 004–0 · 079% for CD8 + T cells.
These were the first documented breakthrough infections with the omicron variant in fully vaccinated individuals after receiving booster vaccine doses. Some of these individuals had received heterologous vaccine doses in accordance with new global practice. Booster doses were administered 21-37 weeks after the second vaccine dose, and breakthrough infections occurred 22-59 days thereafter. At the onset of their breakthrough infections, all subjects had high levels of viral spike protein binding antibodies corresponding to levels reported 4 weeks after the second vaccine dose.
6
- Group D
- Gazit S
- writes L
- et al.
Kinetics of SARS-CoV-2 anti-S IgG after BNT162b2 vaccination.
and as expected after receiving booster vaccine doses.
7
- Demonbreun AR
- Sancilio A
- Vaught LA
- et al.
Antibody titers before and after booster doses of SARS-CoV-2 mRNA vaccines in healthy adults.
Viral RNA strains in omicron variant infections have not yet been reported. It is still unknown whether the viral strains observed in our group are different from those in unvaccinated or differently vaccinated individuals. During wild-type SARS-CoV-2 infection, a mean viral RNA load of 5.83 log
10 viral RNA copy pr. inoculation was found in samples taken up to the day after the onset of symptoms,
8
- Wölfel R
- Corman VM
- Guggemos W.
- et al.
Virological assessment of inpatients with COVID-2019.
with a maximum of 8 · 85 log10 viral RNA copy pr. cotton swab. In this group of individuals, an average of 6 · 38 logs10 viral RNA copy pr. ml eluted inoculum was detected with the highest viral load (8.22 log)10) detected on day 4 after the onset of symptoms. This suggests that the individuals were contagious, consistent with the presence of infection clusters that did not spare either member of the two groups.
Specific T cell responses were detected in all tested participants at least 2 weeks after symptom onset, in the interval reported after vaccination.
9
- Keeton R
- Richardson SI
- Moyo-Gwete T
- et al.
Previous infection with SARS-CoV-2 boosts and expands the immunogenicity of Ad26.COV2.S in a variant-dependent manner.
with additional T cell responses to the viral nucleocapsid and membrane proteins.
The mild to moderate disease course suggests that full vaccination followed by a booster dose still provides good protection against serious disease caused by omicron. However, we cannot rule out the long-term consequences of COVID-19. In addition, our findings are limited to a low number of individuals in relatively young and otherwise healthy individuals (n = 7). This case series adds further evidence that omicron, as predicted, is capable of avoiding immunity induced by mRNA vaccines in vivo. South Africa only recently introduced booster vaccinations for individuals immunized with two doses of BNT162b2, so the presence of this group from Germany provided a unique opportunity to study omicron breakthrough infections in individuals with mRNA vaccine boosters.
In vitro data suggest lower titers of neutralizing antibodies to omicron compared to other SARS-CoV-2 lines after BNT162b2 vaccination, but increased titers after a third dose.
10
- S
- Jackson L
- Khan K |
- et al.
Omicron largely, but incompletely, escapes Pfizer BNT162b2 neutralization.
,
11
- Wilhelm A
- Widera M
- Grikscheit K
- et al.
Reduced neutralization of SARS-CoV-2 omicron variant of vaccinesera and monoclonal antibodies.
,
12
Pfizer
Pfizer and BioNTech provide update on the omicron variant. Press release.
supports calls for booster doses, while the omicron variant appears to be spreading globally. However, our study shows insufficient prevention of symptomatic infection in otherwise healthy individuals who had received three doses of COVID-19 mRNA vaccines.
These results support the need for updated vaccines to provide better protection against symptomatic omicron infection
13
BioNTech says it can adjust the Covid vaccine to 100 days if needed.
and emphasize that non-pharmaceutical measures should be maintained. Encouragingly, early data from South Africa suggest that the efficacy of the BNT162b2 vaccine against hospitalization is maintained or reduced.
14
- Collie S
- Champion J
- Moultrie H
- Bekker LG
- Gray G
Efficacy of BNT162b2 vaccine against omicron variant in South Africa.
CK and CKM contributed equally. We declare no competing interests.
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N Engl J Med. 2021; ()
Article info
Release history
Published: January 18, 2022
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DOI: https://doi.org/10.1016/S0140-6736(22)00090-3
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