The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant posed a severe threat to the hope of ending the outbreak by large-scale vaccination. A new Lancet preprint research paper discusses the effectiveness of the Pfizer-BioNTech BNT162b2 vaccine in reducing the load imposed by the surging number of cases of Omicron infection in healthcare facilities.
Study: BNT162b2 (Pfizer–Biontech) mRNA COVID-19 Vaccine Against Omicron-Related Hospital and Emergency Department Admission in a Large US Health System: A Test-Negative Design. Image Credit: diy13 / Shutterstock.com
Background
The SARS-CoV-2 Omicron variant contains more mutations in the spike receptor-binding domain (RBD) than any other variant of this virus. Many of these mutations have occurred in earlier strains and were linked to higher transmissibility and antibody escape.
Previous studies have indicated that full vaccination with the BNT162b2 vaccine was found to be relatively ineffective in protecting against the Omicron variant. An additional booster dose increased neutralizing activity against Omicron; however, these levels remained lower than those against the SARS-CoV-2 wild-type or Delta variants. Despite this, T-cell responses to the vaccine or natural infection remain protective against Omicron.
It remains unclear how neutralizing activity and T-cell responses correlate with actual vaccine effectiveness (VE) against SARS-CoV-2 infection, as well as both symptomatic and severe presentations of the coronavirus disease 2019 (COVID-19). However, preliminary data on real-world VE from many parts of the world indicate low levels of protection for a limited period against infection and symptomatic/severe disease with Omicron infection following double vaccination with the BNT162b2 vaccine.
With the third dose of any messenger ribonucleic acid (mRNA) vaccine, VE increases against infection and symptomatic disease, with 90% protection against hospitalization, but wanes after one month. The current study aimed to assess the VE of two and three doses of the BNT162b2 vaccine against Omicron-related hospitalizations and emergency department (ED) admissions.
Study findings
The current study was conducted between December 1, 2021, and January 11, 2022. A total of 14,137 patients were included in the current study who either tested negative for SARS-CoV-2 or were determined to be infected with the dominant lineage at the time when they presented with COVID-19 symptoms.
Taken together, 21.6% of the total study population had a positive SARS-CoV-2 test, of which 49.4% and 50.6% of individuals were identified as being infected with the Delta and Omicron variants, respectively.
Over 35% of the 14,137 patients were unvaccinated, whereas 38.5% had received two BNT162b2 doses and 26.4% had received three doses of this vaccine. About 43% of patients were admitted to the hospital, whereas 57% were admitted to the ED without subsequent hospital admission. Of those who were hospitalized, about 54% were infected by the Delta variant and the remainder of patients were infected by Omicron, with roughly equal proportions of ED admissions being due to these variants.
At three months from receiving the second vaccine dose, BNT162b2 prevented 80% of Delta-related ED admissions. This number dropped to only 63% at six months or more following the second dose. Similarly, a two-dose vaccination regimen prevented 88% and 74% of hospitalizations at three months and six months, respectively.
For the Omicron variant, the corresponding two-dose protection against ED and hospital admission was 60% and 68%, respectively, at three months. This VE was reduced to 40% at six months. After three doses, hospitalizations caused by Delta were reduced by 88% and 93% for ED and hospital admission, respectively.
For Omicron, the third dose of BNT162b2 prevented 78% of ED admissions at three months and 48% after three months. VE against Omicron-related hospitalization increased to almost 90% with a third dose.
Interestingly, the protective effect of the BNT162b2 vaccine against hospitalization did not wane after either two or three doses of BNT162b2. In vitro markers of T-cell immunity also appear to remain intact against Omicron after the second dose.
Implications
The two-dose efficacy of BNT162b2 against ED visits was reduced for both Omicron and Delta infections, which agrees with early reports of vaccine escape by these variants against infection and symptomatic disease. The overall VE against ED admissions was less for Omicron.
However, ED visits fell by 88% for Delta and 76% for Omicron after an additional BNT162b2 dose, with the immunity remaining steady at 81% VE at three or more months from the third dose. Protection against Omicron infection decreased by half at about three months after the third dose, which also corroborates with earlier reports of waning protection against asymptomatic Omicron infection after the third dose.
Protection against hospitalization was also lower for Omicron as compared to Delta at the peak VE after two doses.
The researchers concluded that two-dose BNT162b2 regimens should no longer be recommended, as a third booster dose is required against Omicron. A third dose provides a high level of immunity at about 90%.
Conclusions
The concept of a third dose became popular to boost protection against the Delta variant. However, the results of the current study indicate a high level of protection of three BNT162b2 vaccine doses against the Omicron variant to reduce infection, symptomatic illness, and severe COVID-19.
Neutralizing antibody titers also rose after the third dose to higher levels than those that were achieved at any point following the second dose.
At present, Omicron is the dominant circulating strain in most of the world, thereby making increasing the urgency of providing a third booster dose to as many people as possible. However, efforts to develop specific boosters based on BNT162b2 or other mRNA vaccines specific to the Omicron variant are currently in development.
The aim of such boosters is to avert mild-severe COVID-19 due to Omicron, which is currently spreading at unprecedented rates, and thus improve the social and economic status of the region.
“Our results suggest that effectiveness of a third dose against omicron-related hospitalization appears durable, but studies with longer duration of follow-up after receipt of a booster dose are needed—and early signs of waning effectiveness against omicron-related hospital admission may be emerging.”
*Important notice
Preprints with The Lancet publish 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.
