#17,135
It's no secret that the highly divergent Omicron variant (see above graphic) - which appeared abruptly a year ago in South Africa - greatly undermined the effectiveness of our COVID vaccines which were developed against the original strain of SARS-CoV-2.
While the evidence suggests that these vaccines can still reduce the severity of infection, they aren't particularly good at preventing infection (or reinfection) by these newer Omicron subvariants.
As a result, last July the FDA Recommended Adding BA.4/5 Spike Protein To Create A Bivalent COVID Booster Shot for this fall in the United States. While the results are still coming in, some evidence suggests these bivalent boosters may be more effective than their predecessors against Omicron.
All of this is a concern because there is mounting evidence (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection) that repeated infections with COVID can significantly increase the risks of being hospitalized or dying.
We've seen similar loss of effectiveness in therapeutics - like monoclonal antibodies - developed against the original COVID strains as well, which continue to erode our treatment options.
Today the ECDC has published an interim analysis on the effectiveness of the COVID Vaccine (and booster) in HCWs in Europe before the release of the new bivalent booster shots.
This is not a comparison of vaccinated vs. unvaccinated, but rather between vaccinated and boosted, as the following excerpt explains:
Considering the very high COVID-19 vaccine coverage rates, with nearly all HCWs having received at least one dose of vaccine before enrolment (see Table 1 below), comparing the incidence of SARS-CoV-2 infection or COVID19 disease in vaccinated and unvaccinated groups was not possible.
Therefore, the rates in HCWs who had received any booster dose with those of the HCWs who had received a primary course of vaccination more than three months since the last dose of primary course vaccination were compared. Due to the specific features of the Omicron variant, the analysis was also restricted to HCWs who were followed up before or after 15 December 2022, when the first cases of the Omicron variant were identified in the study, defining the waves dominated by Delta (3 May 2021 to 14 December 2021) and Omicron (15 December 2021 to 19 July 2022).
This is a lengthy (21-page PDF), and detailed report, which helps to quantify what we already knew; that the original COVID boosters weren't very effective in preventing breakthrough infection from the newer Omicron subvariants.
Interim analysis of COVID-19 vaccine effectiveness in healthcare workers, an ECDC multi-country study, May 2021–July 2022
Monitoring
21 Nov 2022
This document reports on one of ECDC’s multi-country studies in the hospital setting to measure product-specific COVID-19 VE against any laboratory-confirmed SARS-CoV-2 infection among healthcare workers (HCWs) eligible for vaccination.
Executive summary
- ECDC is building infrastructure to allow the regular monitoring of COVID-19 vaccine effectiveness (VE) over time, using a multi-country approach that involves studies implemented in different settings [1,2].
- As of July 2022, 16 hospital sites (in Croatia, Estonia, Greece, Ireland, Italy, Latvia, Poland, Portugal, and Spain) have participated in the study, covering the period from 3 May 2021 to 19 July 2022. In this period, the study teams approached 2 832 HCWs, enrolled 2 629 of them, and followed up with 2 369 . Aside from 18 HCWs who remained unvaccinated during the study period, all other HCWs recruited to date have been vaccinated with one or more doses of COVID-19 vaccines at enrolment. Nearly two thirds (64%) of them have received a booster dose.
- At enrolment, over a quarter (26%) of the HCWs reported having had a COVID-19 infection, of which the majority (87%) were diagnosed 46 or more days prior to enrolment. Serological results have been reported by 11 sites, of which all reported detection of anti-spike antibodies in >90% of HCWs at enrolment.
- Genetic sequencing data for breakthrough infections have been submitted for 176 HCWs from eight sites, of which 116 were Omicron variant infections (B.1.1529) isolated since 15 December 2021. Thirty were Delta variant infections isolated between May 2021 and January 2022.
- Omicron variant BA.1 was isolated until May 2022, when it was replaced by BA.2, which was subsequently replaced in June 2022 by BA.4/5.
- Among HCWs who had received only the primary vaccination schedule, 196 SARS-CoV-2 infections were reported, representing a cumulative incidence of 2.9 per 1 000 person days, and 257 SARS-CoV-2 infections were reported among those who had a received a booster dose, representing a cumulative incidence of 2.7 per 1 000 person days.
- The adjusted rVE was 7% (95%CI: -28% to 32%) overall, while the adjusted rVE was 11% (95%CI: -48% to 47%) in the HCWs reporting a previous COVID-19 episode before enrolment and -6% (95%CI -81% to 38%) in HCWs without a previous COVID-19 episode.
- These results are in line with published evidence indicating that current COVID-19 vaccines have low effectiveness against mild Omicron infections, including after a booster dose. While this analysis does not include VE against severe disease, published literature indicates that VE against severe disease due to the Omicron variant is high following the administration of both the primary course and further maintained by a booster dose. Although point estimates of VE indicated some protective effects, the wide confidence intervals make the interpretation of the results difficult. The precision of the rVE estimates may improve through the continuation of the study in the participating sites (longer follow-up) or through the recruitment of new sites to increase the size of the HCW cohort.
Discussion and conclusions
Aside from 18 unvaccinated HCWs, all HCWs recruited to date have been vaccinated with one or more doses of COVID-19 vaccine. In this report, the estimation of relative VE is restricted to the population of HCWs who had completed a primary vaccination schedule and compared the incidence of laboratory-confirmed SARS-CoV-2 infections among those HCWs who had received any booster dose to those with primary course vaccination.
The estimation of relative VE is further restricted to the period of 15 December 2021 to 19 July 2022, a period of intense circulation of the Omicron variant, to account for the skewed distribution over time of the number of cases, the known epidemic differences between the Delta and Omicron waves [17-18] and the expected infection in vaccinated individuals [19].
In this study, the overall relative VE against infection of a booster dose compared to primary course vaccination, adjusted for key variables, suggested no significant protection offered by the booster dose compared to a completed primary series of vaccination, although the confidence intervals were wide.
Available evidence from the literature indicates that current COVID-19 vaccines have low effectiveness against mild and asymptomatic Omicron infections. The protection against infection due to the Omicron variant starts waning two to three months after completing the primary series and is largely lost after six months.
It was found that protection against infection also wanes rapidly after the first booster dose. The literature also shows that a second booster improves VE against infection, but this also seems to wane rapidly, as has been seen within the short follow-up period available so far after the second booster dose. In summary, the benefit of booster doses to protect against SARS-CoV-2 infection is seemingly limited [20].
Available evidence shows that the vaccine-induced protection is stronger and more durable against severe disease, although the balance of the evidence indicates gradual waning three to six months after the primary series. Studies of VE against severe disease due to the Omicron variant by time since first booster suggest that relative vaccine effectiveness against severe outcomes is high following the administration of a booster dose, and for up to two to three months after receiving the booster. Only a few studies with a follow-up time longer than six months are available, but the available limited evidence indicates that the vaccines provide protection against severe outcomes also more than six months after the first booster dose.
The first booster dose, usually administered four to six months after completion of the primary series, serves to improve the immune response after it has waned over time, as does the second booster. However, the incremental benefit of a second booster dose is likely lower compared to the primary series and first booster doses, including for severe disease [20].
Evidence from studies looking at the combined effect of naturally-acquired immunity and vaccine-induced immunity clearly point to an extra layer of protection for those with hybrid immunity. However, the scale of naturally acquired immunity in populations is difficult to quantify due to issues such as the under-ascertainment of COVID19 cases and reinfections, the lack of unbiased, longitudinal seroprevalence data, and the waning profiles of protection. In addition, few vaccine effectiveness studies disaggregate results by prior infection status. For those that do, direct comparison between studies is challenging, owing to heterogeneity (type of study, study population, type of vaccine, follow-up time, sequence of infection/vaccination) [20].
The findings from this study indicate that both vaccination with the primary series only and with booster doses appeared to offer more protection to HCWs reporting a COVID-19 episode prior to enrolment than those HCWs without a previous COVID-19 episode, in agreement with other studies [21]. Continuation of the study will increase the precision of the estimates and contribute to providing data to inform public health decisions in the anticipated SARS-CoV-2 waves in 2022 and 2023.
Hopefully, the new bivalent booster shot will fare better against these Omicron variants.
Time will tell.
But the emergence of Omicron should remind us that the SARS-CoV-2 virus continues to evolve, and there is nothing to say that we couldn't see another radical evolutionary leap in the future.
