Studies assess association between 3 doses of COVID-19 vaccine and infection and death caused by SARS-CoV-2 Omicron and Delta variants

Findings from a study published in JAMAsuggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

"For 3 doses vs unvaccinated, the ORs corresponded to an estimated effectiveness (1 – odds ratio [OR]) of 67.3% (95% confidence interval [CI], 65.0%-69.4%) for Omicron and 93.5% (95% CI, 92.9%-94.1%) for Delta. For 3 doses vs 2 doses, the ORs corresponded to an estimated relative effectiveness of 66.3% (95% CI, 64.3%-68.1%) for Omicron and 84.5% (95% CI, 83.1%-85.7%) for Delta," reported Emma K Accorsi, Centers for Disease Control and Prevention COVID-19 Response, Atlanta, Georgia, and colleagues. 

"For Omicron, the similarity between ORs for 3 doses using the unvaccinated referent group and the 2-dose referent group is consistent with the attenuation of the OR for 2 doses vs unvaccinated with time since second dose, which reflected no significant association by 6 months after second dose for both products. For Delta, the association between infection and 2 doses vs unvaccinated also attenuated over time since second dose, which is consistent with previous reports; however, the ORs were statistically significant even up to 11 months after the second dose," the researchers noted. 

The researchers performed a test-negative case-control analysis among adults 18 years or older with COVID-like illness tested from December 10, 2021, through January 1, 2022, by a national pharmacy-based testing programme (4,666 COVID-19 testing sites across 49 US states).

Overall, 23,391 cases (13,098 Omicron; 10,293 Delta) and 46,764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2,441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18,587) of controls. Meanwhile, prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7,245) of Omicron cases, 44.4% (n = 4,570) of Delta cases, and 41.6% (n = 19,456) of control; meanwhile, being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5,044), and 18.6% (n = 8,721) of cases, respectively. 

For vaccination history, the most common combination of 2 doses was BNT162b2/BNT162b2 (63.4% of 2-dose regimens), followed by mRNA-1273/mRNA-1273 (36.4%), while the most common 3-dose combination was BNT162b2/BNT162b2/BNT162b2 (57.5% of 3-dose regimens). Among individuals receiving 2 vaccine doses only, the median time between the second dose and test date was 8 months. Among those receiving 3 vaccine doses, the median time between the second and third dose was 7 months, and between the third dose and test date was 1 month.

The adjusted odds ratio for individuals who received 3 doses of vaccine compared with those who were unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta. In comparison with individuals who received 2 vaccine doses, the adjusted odds ratio among those receiving 3 vaccine doses was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta.

The researchers also observed that median cycle threshold values were significantly higher in cases occurring in individuals who had received 3 vaccine doses compared to those who received 2 vaccine doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24).

"Although these findings provide evidence supporting that 3-dose schedules are protective and that booster doses are more protective than primary series alone, the significantly higher OR for Omicron suggests that booster doses are less protective against Omicron than against Delta. These results are consistent with in-vitro neutralisation assays that suggested the potential for immune evasion with Omicron," the researchers noted, adding that "[these findings] also highlight that, in the setting of Omicron, higher booster coverage rates may be needed to achieve the same public health benefit as during Delta predominance. Additionally, nonpharmaceutical interventions may provide an important adjunct to slow the spread of Omicron."

Similarly, findings from the US Centers for Disease Control and Prevention's (CDC) latest Morbidity and Mortality Weekly Report show that protection against infection and death during the Delta-predominant period against infection during Omicron emergence were higher among booster vaccine dose recipients, and especially among persons aged 50–64 and ≥65 years.

To assess the impact of full vaccination with additional and booster doses (booster doses), case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April–May 2021), Delta emergence (June 2021), Delta predominance (July–November 2021), and Omicron emergence (December 2021) periods in the United States. Weekly COVID-19 cases (April 4–December 25, 2021) and associated deaths (April 4–December 4, 2021) by vaccination status, including additional and booster doses starting October 3, were reported from 25 state and local health departments that routinely link case surveillance to vaccination data from immunisation registries. 

During April 4–December 25, 2021, a total of 6,812,040 COVID-19 cases among unvaccinated persons and 2,866,517 cases among fully vaccinated persons were reported among persons aged ≥18 years in 25 US jurisdictions, while 94,640 and 22,567 COVID-19-associated deaths among unvaccinated and fully vaccinated persons, respectively, were reported by December 4. 

The age-standardised IRR for cases in unvaccinated versus fully vaccinated persons was 13.9 during April–May and progressively declined to 8.7 during June, 5.1 during July–November, and 3.1 during December, coinciding with the periods of Delta emergence, Delta predominance, and Omicron emergence, respectively. This decline suggests a change in crude vaccine effectiveness (VE) for infection from 93% during April–May, to 89% during June, 80% during July–November, and to 68% during December. Age-standardised IRRs for deaths among unvaccinated versus fully vaccinated persons were relatively stable; crude VE for deaths was 95% during April–May, 94% during June, and 94% during July–November.

Meanwhile, age-standardised case IRRs among unvaccinated persons compared with fully vaccinated persons with a booster dose declined from 13.9 during October–November to 4.9 during December, representing potential decreases in crude VE for infection from 93% to 80%, respectively. Comparing unvaccinated persons with fully vaccinated persons without a booster dose, age-standardised case IRRs during October–November and December were 4.0 and 2.8 respectively, representing decreases in VE from 75% to 64%. During October–November, age-standardised IRRs for deaths among unvaccinated persons were 53.2 compared with those in fully vaccinated persons with a booster dose and 12.7 compared with persons without a booster dose; these results represented crude VE against death of 98% and 92%, respectively.

Further, the report noted that booster doses provided the largest gains in protection among persons aged ≥65 years followed by persons aged 50–64 years when compared with those aged 18–49 years.

"Early analysis of surveillance data provided crude signals of VE that were consistent with other studies reporting decreased VE against Omicron infection compared with Delta and increased protection from booster doses compared with a primary series of COVID-19 vaccination alone. Ongoing analyses will help monitor the impact of the Omicron variant and other emerging variants on VE against COVID-19 cases and associated deaths," the report concluded.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
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