Immunization against COVID-19 began in Qatar in December 2020, with the Pfizer-BioNTech and then Moderna vaccines being distributed firstly to frontline healthcare workers and the most vulnerable. As of August 2021, it is estimated that more than 80% of all individuals aged over 12 have received two doses of either mRNA vaccine, but despite this, SARS-CoV-2 infections are reportedly on the rise in the region.
In a paper recently uploaded to the preprint server medRxiv* by Chemaitelly et al. (August 27, 2021), the long-term effectiveness of the mRNA vaccines is analyzed amongst the Qatar population. The study observed waning protection against infection around six months post-vaccination but lasting protection from death and hospitalization.
How was the study performed?
The group utilized information from the national Qatar SARS-CoV-2 database, including all PCR testing, vaccination, and related demographic data for each individual since the beginning of the COVID-19 pandemic. The effectiveness of the vaccine was estimated by comparing infection rates, disease severity, and vaccination status. Only individuals who received two doses of the Pfizer-BioNTech vaccine were included in the study to remove some variability originating from heterogeneous dosing.
Positive PCR tests wherein the individual reported no symptoms were considered asymptomatic, and vaccine effectiveness was also reported against the probability of developing symptoms, with further analysis based on age, sex, race, and SARS-CoV-2 variant. Owing to the average young population of Qatar, the average age of participants was 31.5 years old, around 70% of which were male, with other demographics representing the general population proportionately.
Data from around 200,000 individuals were included in the study, and the authors state that as of August 15, 2021, 8,155 individuals that had received only one dose of the Pfizer-BioNTech vaccine had since become infected with SARS-CoV-2, while 8,935 individuals that had received both doses became infected. During the early stages of vaccine distribution, the percentage of individuals with breakthrough infections was very low, below 5%, given the low proportion of the population yet vaccinated. During the peak of the beta variant wave in the country in April 2021, breakthrough cases rose to almost 15% and have since risen to over 35% in an erratic fashion.
Around three-quarters of all breakthrough, cases were amongst those receiving the Pfizer-BioNTech vaccine rather than the Moderna vaccine, though around twice as many individuals have received the former, mainly the earliest and most vulnerable, introducing bias. Amongst those that have received just one dose of the Pfizer-BioNTech vaccine, 377 individuals have been hospitalized with severe COVID-19 as of August 15, compared to 96 that had received both, with a similar ratio amongst the critically ill: 31 and 8, and amongst the deceased: 34 and 15.
Protection against infection and death
As with other reports, the authors state that vaccine efficacy against infection is negligible for two weeks following the first dose, reaching a peak of around 70% protection five weeks after the second dose. This study reports that effectiveness, in fact, declines slightly in weeks 0-4 following the second dose, then declining more quickly after week 15 with little variation based on sex, age, or race. Effectiveness against symptomatic infection was noted to follow a similar decline, peaking around five weeks after receiving the second vaccine dose and then declining steadily, more quickly at 15-20 weeks. Protection against symptomatic infection was consistently higher than against asymptomatic infection, however, peaking at almost 80% compared to 63.7%.
Importantly, the decline in effectiveness against hospitalization or death was far less significant, not declining until 25 weeks post-second dose. Protection against hospitalization and death was found to remain stable at around 90% for six months post-vaccination, seen to decline to around 70% at later time-points. As these later time points reflect the most vulnerable amongst the population, the first to be vaccinated, they may be biased by other comorbidities and an increased probability of infection. However, the group state that the same pattern of waning protection was observed amongst all age groups, and therefore is likely to be representative of the general population.
Protection against variants of concern
Qatar experienced two large SARS-CoV-2 waves during 2021, the first characterized by a mixture of alpha and beta variants of concern, while the latter was dominated by the highly transmissible delta variant. The vaccine's efficacy for several thousand individuals each infected with the alpha, beta, or delta variants as confirmed by genomic testing was also compared on a weekly basis. For example, 5-9 weeks following the second dose, the vaccine provided 82.2% protection against infection from the alpha variant, 52.7% from the beta, 72.0% from the delta, while at weeks 15-19, protection levels were 11.9%, 47.7%, and 13.0%, respectively.
The possibility of waning protection due to exposure to new variants of concern was also dismissed by the group, given the observed drop in effectiveness when tracking individuals infected with each specific strain. Qatar, Israel, and the USA implemented a shorter three-week interval between vaccine doses. These countries have reported waning protection from the mRNA vaccine more greatly than the UK and Canada, which executed a more delayed vaccination schedule. The authors speculate that this may explain the disparity in reports observed between these locations, though this is yet to be confirmed.
A large portion of the vaccinated population is likely to be on the verge of a significant drop-off in vaccine-induced protection against infection with SARS-CoV-2, given the timing of most wide-scale vaccination programs around the world that initiated in early 2021. While this study has found that protection from hospitalization and death is longer-lasting, boosters may be required to reinforce this and avoid protection waning further.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.