CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance† (1–5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites§ examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).¶ Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits.
VISION Network methods have been previously published (6). Eligible medical encounters were defined as those among adults aged ≥18 years with a COVID-19-like illness diagnosis†† who had received molecular testing (primarily reverse transcription-polymerase chain reaction assay) for SARS-CoV-2, the virus that causes COVID-19, during the 14 days before through 72 hours after the medical encounter. The study period began on August 26, 2021, 14 days after the first U.S. recommendation for a third mRNA COVID-19 vaccine dose.§§ The date when the Omicron variant accounted for ≥50% of sequenced isolates was determined for each study site based on state and national surveillance data. Recipients of daypg.com2.S (Janssen [Johnson & Johnson]) vaccine, 1 or >3 doses of an mRNA vaccine, and those for whom <14 days had elapsed since receipt of any dose were excluded.
See more: Covid 19 omicron
VE was estimated using a test-negative design, comparing the odds of a positive SARS-CoV-2 test result between vaccinated and unvaccinated patients using logistic regression models conditioned on calendar week and geographic area and adjusting for age, local virus circulation, immunocompromised status, additional patient comorbidities, and other patient and facility characteristics.¶¶ Immunocompromised status was identified by previously published diagnosis codes.*** Vaccination status was categorized based on the number of vaccine doses received and number of days between receipt of the most recent vaccine dose and the index medical encounter date (referred to as time since vaccination).††† Patients with no record of mRNA vaccination before the index date were considered unvaccinated. Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster).
View more: The Mauricio Pochettino admission that gives Antonio Conte and Tottenham Champions League boost
A standardized mean or proportion difference ≥0.2 indicated a nonnegligible difference in distributions of vaccination or infection status. The most remote category of time since vaccination was either ≥4 months or ≥5 months, depending on data availability (no hospitalizations were observed ≥5 months after receipt of a third dose during either period). To test for a trend in waning, time since vaccination categories were specified as an ordinal variable (<2 months = 0; 2-3 months = 1; 4 months = 2; ≥5 months = 3), with statistically significant waning indicated by a p-value <0.05 for the resulting regression coefficient. SAS (version 9.4, SAS Institute) and R software (version 4.1.2, R Foundation) were used to prepare data and perform statistical analysis.
For illustration purposes, the earliest and latest VE estimates for the trend are described. The overall trend can be statistically significant even though the precision of each estimate might be low, with the 95% CIs of estimates including zero. Analyses were stratified by two periods: Delta variant predominance and Omicron variant predominance. This study was reviewed and approved by the institutional review boards at participating sites and under a reliance agreement with the Westat, Inc. Institutional Review Board.§§§
Among 241,204 eligible ED/UC encounters, 185,652 (77%) and 55,552 (23%) occurred during the Delta- and Omicron-predominant periods, respectively (Table 1). Among persons with COVID-19-like illness seeking care at ED/UC facilities, 46% were unvaccinated, 44% had received 2 doses of vaccine, and 10% had received 3 doses. The median interval since receipt of the most recent dose before the ED/UC encounter was 214 days (IQR = 164-259 days) among those who had received 2 doses and 49 days (IQR = 30-73) among those who had received 3 doses (CDC, unpublished data, 2022).
During the Delta-predominant period, VE against laboratory-confirmed COVID-19-associated ED/UC encounters was higher after receipt of a third dose than after a second dose; however, VE declined with increasing time since vaccination (Table 2). Among recipients of 3 doses, VE was 97% within 2 months of vaccination and declined to 89% among those vaccinated ≥4 months earlier (p<0.001 for test of trend in waning VE).
View more: U.S. Relations With Russia
During the Omicron-predominant period, VE against COVID-19-associated ED/UC encounters was lower overall compared with that during the Delta-predominant period and waned after the second dose, from 69% within 2 months of vaccination to 37% at ≥5 months after vaccination (p<0.001). Protection increased after a third dose, with VE of 87% among those vaccinated within the past 2 months; however, VE after 3 doses declined to 66% among those vaccinated 4-5 months earlier and 31% among those vaccinated ≥5 months earlier, although the latter estimate is imprecise because few data were available on persons vaccinated for ≥5 months after a third dose. The decreasing trend of VE with increasing time since vaccination was significant (p<0.001).
Among 93,408 eligible hospitalizations, 83,045 (89%) and 10,363 (11%) occurred during the Delta- and Omicron-predominant periods, respectively (Table 3). Among persons hospitalized with COVID-19-like illness, 43% were unvaccinated, 45% had received 2 vaccine doses, and 12% had received 3 doses. The median interval since receipt of the most recent dose before hospitalization was 216 days (IQR = 175-257 days) among those who had received 2 doses and 46 days (IQR = 29-67 days) among those who had received 3 doses, (CDC, unpublished data, 2022).
During the Delta-predominant period, 2-dose VE against laboratory-confirmed COVID-19-associated hospitalizations declined with increasing time since vaccination and increased after a third dose (Table 2). Among recipients of 3 doses during the Delta-predominant period, VE against COVID-19-associated hospitalizations declined from 96% within 2 months of vaccination to 76% among those vaccinated ≥4 months earlier although the latter estimate is imprecise because few data were available on persons vaccinated for ≥4 months after a third dose during the Delta-predominant period (p<0.001 for test of trend in waning VE).
During the period of Omicron predominance, VE against COVID-19-associated hospitalizations was lower overall and waned with time since vaccination: VE after a second dose declined from 71% within 2 months of vaccination to 54% among those vaccinated ≥5 months earlier (p = 0.01). Among recipients of 3 doses, VE against COVID-19-associated hospitalizations declined from 91% among those vaccinated within the past 2 months to 78% among those vaccinated ≥4 months earlier (p<0.001).
