Increasing COVID-19 Breakthrough Deaths In UK Prompted Study That Finds AstraZenaca Vaccines Is Associated With Increased Breakthrough Risk Compared To Pfizer!
As infection, hospitalization and mortality rates continue to rise in the United Kingdom, even among the fully vaccinated, medical experts are starting to worry about the waning immune protection offered by these vaccines.
In the UK COVID-19 vaccine surveillance reports for Weeks 43 to 45, compiled data showed that despite the rate of deaths being substantially lower in vaccinated groups;, 79% of recent coronavirus disease 2019 (COVID-19) deaths in the U.K. have occurred as a result of breakthrough infections in double vaccinated individuals at least 14 days prior to the positive SARS-CoV-2 test.https://www.gov.uk/government/publications/covid-19-vaccine-weekly-surveillance-reports
It should be noted that the Astrazenaca or ChAdOx1 COVID-19 vaccine is main vaccine being used in the United Kingdom.
The breakthrough infections, hospitalizations and mortality rates among the fully vaccinated prompted researchers from the University College London-UK, Lancaster University-UK, Liverpool School of Tropical Medicine-UK and London School of Hygiene and Tropical Medicine-UK to conduct a new study on the level of antibodies following vaccination and trajectories of waning that may differ between vaccines influencing the level of protection and as to when protection is reduced and, consequently the optimum timing of booster doses.
The study findings surprising found that the AstraZenaca vaccines or ChAdOx1 nCoV-19 are associated with an increased breakthrough risk compared to Pfizer’s vaccines or BNT162b2!
The study findings showed that anti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates one would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2.
The study findings showed an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with the study data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2.
The study findings demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritized to those who received ChAdOx1 as their primary course.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.11.05.21265968v1
The study team observed substantially lower levels of anti-spike protein antibodies (anti-S) and subsequent higher risk of severe acute respiratory disease syndrome coronavirus 2 (SARS-CoV-2
) breakthrough infections following the second dose of ChAdOx1 nCoV-19 (AstraZeneca/Oxford) vaccine as compared to BNT162b2 (BioNTech/Pfizer) vaccine.
The research team studied individuals recruited in the ‘Virus Watch’ community cohort who had received their second dose of either ChAdOx1 or BNT162b2 vaccine.
The study team stressed that understanding the timeline of antibody waning is crucial.
The SARS-CoV-2 vaccines are designed to stimulate the production of antibodies targeting the spike protein of SARS-CoV-2. The level of antibodies following vaccination and trajectories of waning may differ between vaccines, thus influencing the level of protection, how soon protection is reduced, and, as a result, the optimum timing of booster doses.
Despite the rate of deaths being substantially lower in vaccinated groups; alarmingly 79% of recent coronavirus disease 2019 (COVID-19) deaths in the U.K. have occurred as a result of breakthrough infections in double vaccinated individuals at least 14 days prior to the positive SARS-CoV-2 test.
Considering the high levels of breakthrough infections and subsequent deaths occurring in double vaccinated individuals, it is important to understand trajectories of anti-S waning in individuals after they have received their second dose of the COVID- 19 vaccine.
Additionally, it is important to determine whether the timing of their second dose can be used as a correlate of protection for SARS-CoV-2 infection in an effort to inform vaccine policies around the world.
The study findings showed how antibody waning vary by vaccine type, demographic and clinical characteristics.
In the study, anti-S levels were compared between ChAdOx1 and BNT162b2 vaccine recipients by time since vaccination, age, sex, and clinical vulnerability.
In all, a total of 24,049 samples from 8,858 individuals, 5,549 of whom received a second dose of ChAdOx1 and 3,205 received BNT162b2 vaccines, who remained anti-nucleocapsid (anti-N) antibody negative, were included in the analysis of anti-S waning over time.
It was noted that anti-S levels peaked following the second dose of vaccine and were nine-fold higher for BNT162b2 as compared to ChAdOx1. Later, waning anti-S levels followed a log-linear decline from three weeks after the second dose of vaccination.
Interestingly at 20 weeks after the second dose of the vaccine, mean anti-S levels were 1521 U/ml for BNT162b2 and 342U/ml for ChadOx1 recipients. However, the overall rates of waning were higher in BNT162b2 recipients as compared to those who had received the ChAdOx1 vaccine.
It was also noted that there was no evidence of a difference in the rates of waning by age, sex, or clinical risk groups for BNT162b2 or ChAdOx1 vaccines.
Data from 8,275 individuals were analyzed for anti-S levels prior to breakthrough infection to examine anti-S as a correlate of protection against SARS-Cov-2 infection.
Furthermore, these samples were also used to estimate a predicted time to reach a specified anti-S level for a threshold of protection. The study team undertook survival analysis using a Kaplan-Meier descriptive analysis, in addition to a Cox regression model.
Importantly during the timeline for this particular study, the study team observed 197 breakthrough infection cases.
Further, the study team found that individuals with anti-S levels less than 500 U/ml following the second dose were nearly twice as likely to experience a breakthrough infection compared to those with higher levels.
Also, it was found that mean antibody levels declined to the threshold of 500 U/ml after about 3 months for ChAdOx1 and after about 7 months for BNT162b2. Thus, humoral protection wanes to levels associated with breakthrough infections before a 6-month period for those vaccinated with ChAdOx1 but not for BNT162b2.
The detailed analysis included 14,340 participants who reported at least one test result in more than 14 days past the date of receiving their second vaccine dose or by the end of study follow-up.
The study team found an increased risk of breakthrough infections for those who received the ChAdOx1 vaccine as compared to those who received the BNT162b2 vaccine.
Individuals vaccinated with ChAdOx1 had 1.43 increased odds of a breakthrough infection as compared to those doubly vaccinated with BNT162b2.
Interestingly from 20 weeks onwards, the risk of breakthrough infection for BNT162b2 vaccinated individuals is approximately half of ChAdOx1.
Furthermore, anti-S levels may provide an indication of the underlying correlates for this increased risk.
Irrespective, circulating anti-S levels are unlikely to be the only immunological correlate of protection against COVID-19. As humoral immunity wanes, T-cell mediated immunity might act as the source of continued stable protection against infection and severe disease.
Importantly, the timing of SARS-CoV-2 infections included in the current study coincided with the period when the Delta SARS-CoV-2 variant was the main circulating strain in England and Wales. Therefore, the study team highlights that these study findings may relate to many countries currently experiencing an increase in breakthrough infections due to Delta and where the populations have received ChAdOx1 or BNT162b2 vaccines.
The study team concluded, “Together, these study findings suggest that boosting ChAdOx1 earlier than six months after the second dose may be advantageous, particularly in those at greatest risk of severe outcomes.”
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