My bolding of relevant bits.
Vaccines show declining effectiveness against infection overall but strong protection against hospitalization amid delta variant
Results from a trio of studies, published in the CDC’s weekly report, motivated the Biden administration to consider booster shots

Three studies published Wednesday by the Centers for Disease Control and Prevention show that protection against the coronavirus given by vaccines declined in the midsummer months when the more contagious delta variant rose to dominance in the United States.

At the same time, protection against hospitalization was strong for weeks after vaccination, indicating the shots will generate immune fighters that stave off the worst effects of the virus and its current variations.

Data from these studies persuaded the Biden administration to develop a plan for additional doses to bolster the immune systems of people vaccinated months earlier. The Biden administration will begin offering coronavirus booster shots to fully vaccinated adults who received the Pfizer-BioNTech and Moderna shots the week of Sept. 20, top health officials announced Wednesday, after concluding that a third shot is needed to fight off waning immunity.

“Examining numerous cohorts through the end of July and early August, three points are now very clear,” CDC director Rochelle Walensky said at a White House covid-19 news briefing Wednesday. “First, vaccine-induced protection against SARS-CoV-2 infection begins to decrease over time. Second, vaccine effectiveness against severe disease, hospitalization and death remains relatively high. And third, vaccine effectiveness is generally decreased against the delta variant.”

The trio of reports, published Wednesday in the Morbidity and Mortality Weekly Report, the CDC’s scientific digest, also reinforce the idea that vaccines alone will be unable to lift the nation out of the pandemic.

Masks and other precautions should be part of “a layered approach centered on vaccination,” wrote researchers from the New York State Department of Health and the University at Albany School of Public Health in their study of vaccine effectiveness across New York state.

All three reports measure vaccine effectiveness, which compares the rates of infection or hospitalization among vaccinated people with the rates among people who had not been vaccinated. Twenty percent of new infections and 15 percent of hospitalizations from covid-19, the disease caused by the virus, were among vaccinated people.

Until now, evaluations of vaccine effectiveness amid delta largely relied on observations from outside the United States. A recent New England Journal of Medicine study concluded the Pfizer vaccine was 88 percent effective against infections that caused symptoms in England.

Others, such as a study in Israel, found larger declines in protection against infection. One U.S. report that has not yet gone through peer review, collecting data from Mayo Clinic Health System facilities in five states, found a drop in the Pfizer-BioNTech vaccine’s effectiveness against delta infections to 42 percent. The other mRNA vaccine, made by Moderna, was 76 percent effective.

The new study from New York is the first to assess vaccine protection against coronavirus infection across the entirety of a U.S. state amid delta. The study authors found a modest drop in effectiveness: It descended from 92 percent in May to 80 percent in late July.

The second of the three studies found effectiveness against infection declined for nursing home residents after delta emerged. It dropped from 75 percent in March through May to 53 percent in June and July. Vaccination for visitors and staff is crucial, the study authors wrote, and “additional doses of COVID-19 vaccine might be considered for nursing home and long-term care facility residents.”

The third report, an analysis of patients at 21 hospitals in 18 states, found sustained protection against hospitalization. Effectiveness was steady at 86 percent, even in the midsummer months when delta outcompeted other variants of concern. For adults who do not have compromised immune systems, that effectiveness stood at 90 percent.

Many factors influence vaccine effectiveness and the changes the scientists observed in New York cannot be attributed to delta with certitude, they noted.

If vaccinated people behave in riskier ways, such as not wearing masks in crowded areas, that may influence vaccine effectiveness. So might waning immune protections.

To conduct their study, the researchers in New York linked multiple health reporting systems across the state. These included immunization registries, the statewide collection of coronavirus laboratory test results and the system that surveys New York’s inpatient facilities daily. Those databases allowed the study authors to connect vaccine status to every new case and hospitalization reported to the state from May 3 to July 25.

“The New York state data gives us a nice look at how we can link data together when you have comprehensive reporting across a number of systems,” said Robert A. Bednarczyk, an epidemiologist at Emory University Rollins School of Public Health, who has worked with the study authors in the past but was not involved with this research.

By the end of the study period, 66 percent of New Yorkers 18 and older were vaccinated. Vaccine effectiveness against hospitalization remained constant, above 90 percent. And of the more than 48,000 new infections from late spring into summer, 9,675 were in vaccinated people, or about 1 in 5 cases.

But Bednarczyk said breakthrough cases such as these do not mean the vaccines are failing. “The vaccine is doing what it’s supposed to do. It’s priming our immune system,” he said.

Immunized people may still get infected, because the vaccines aren’t perfect. But it is possible immune fighters will sweep the virus out the door much more quickly in a vaccinated person, Bednarczyk said, citing a not-yet-peer-reviewed paper from researchers in Singapore. In that report, vaccinated patients more swiftly defeated an infection compared with those who weren’t.

Though the results in New York may not easily translate to other communities. Maria Sundaram, an infectious-disease epidemiologist at the University of Toronto Dalla Lana School of Public Health, said it is difficult to make comparisons partly because this is an examination of an entire state, not a model that accounts for uncertainties in a population sample.

The change in vaccine effectiveness over time “to about 10 percent lower, I would take with a grain of salt,” Sundaram said, because there may be uncertainty from mismatches between databases or reporting lags.

Studies such as these show that, as valuable as coronavirus vaccines are, they have limits.

“As we’re releasing the brakes on these other non-pharmaceutical interventions” — [meaning masks and other precautions] — “we may see more cases,” Sundaram said. “Vaccines are very, very helpful but they’re not the end-all, be-all of covid-19 prevention.”

The booster shots that will become available in September are designed to be given eight months after people have received their second dose of the Pfizer or Moderna vaccine.

Surgeon General Vivek H. Murthy explained at Wednesday’s White House covid briefing how experts settled on the eight-month time frame, citing data showing that about six months after vaccination, mild to moderate infections started increasing.

Murthy said that while protection against hospitalization and death remained strong at that point, “our anticipation is that if the trajectory that we are seeing continues, that we will likely see in the future an increase in breakthrough hospitalizations and breakthrough deaths. And that’s why we use our judgment to see when to make a determination when that point may be. And that’s how we came to the eight-month mark.”

People who received Johnson & Johnson vaccines may need boosters, too, Murthy said, adding that officials will have more information about additional Johnson & Johnson shots in coming weeks.

The administration announcement drew mixed reaction, with some experts praising the plan and others saying it was premature and could subvert the process for considering vaccines and boosters.

Paul A. Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, questioned the premise of the decision — that a decline in immunity against mild or moderate illness would likely be followed be a decrease in protection against severe disease and hospitalization. He said he believes protection against serious disease might last a few years.

He also said he doubted that boosters would have a major impact on the pandemic, adding that such a change can be brought about only by getting more Americans vaccinated.

In a later news media call with vaccine experts, Offit said he would be more comfortable with the administration plan if data first had been submitted and scrutinized by the CDC and Food and Drug Administration and their outside advisers. “This seems to be a declaration without the vetting you would have liked to have seen,” Offit said.

Standard practice is for the FDA to assess the safety and efficacy of vaccines and for the CDC’s outside advisers, the Advisory Committee on Immunization Practices, to recommend what vaccines Americans should get, and when — not the surgeon general or the National Institutes of Health. After the advisory panel makes its recommendation, the CDC director decides whether to accept it.

Jesse Goodman, former chief scientist at the FDA and professor of medicine and infectious diseases at Georgetown, said he suspects that boosters will be needed and added, “being prepared for a booster campaign makes sense.” But he said it was important for the administration to avoid putting “the cart before the horse.”

Goodman added that it was repeatedly said in the covid-19 briefing that normal processes would prevail, “but I think it puts that process under a date-certain kind of pressure.”

Administration officials stressed in the covid-19 briefing and in subsequent interviews that a booster-shot campaign will not go forward without the go-ahead from the FDA and the CDC advisory committee.

Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021

Summary
What is already known about this topic?

Early observational studies among nursing home residents showed mRNA vaccines to be 53% to 92% effective against SARS-CoV-2 infection.

What is added by this report?

Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%.

What are the implications for public health practice?

Multicomponent COVID-19 prevention strategies, including vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19–associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3–6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant† highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)–certified skilled nursing facilities or nursing homes to CDC’s National Healthcare Safety Network (NHSN)§ were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1–May 9, 2021]), and when the Delta variant predominated¶ (Delta [June 21–August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%–78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10–June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%–73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%–56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

Effectiveness of mRNA COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among nursing home residents was evaluated using data reported to NHSN. CMS-certified nursing homes are required to report aggregate weekly numbers of new laboratory-confirmed SARS-CoV-2 infections among residents, by vaccination status (product and number of doses received), to NHSN. Vaccination status of cases was categorized as 1) unvaccinated (no COVID-19 vaccine doses); 2) fully vaccinated with an mRNA vaccine (2 doses ≥14 days before collection of a SARS-CoV-2–positive specimen), and 3) “other” (single dose of mRNA or Janssen [Johnson & Johnson] vaccine or received unspecified vaccines). Nursing homes also reported weekly on the number of residents by vaccination status; reporting on resident vaccination status was voluntary during the pre-Delta period but was required by CMS starting on June 6, 2021.

Facility-level weekly records for the analysis combined case counts by vaccination status in each week with the weekly number of residents by vaccination status 2 weeks previously. This ensured that residents were counted as fully vaccinated only after ≥14 days from receipt of a second dose. Weekly reports of case counts were excluded if a facility did not report resident counts by vaccination status for the corresponding week 2 weeks earlier. Records from facilities with case data during March 1–August 1, 2021, and the corresponding data on resident vaccination status during February 15–July 18, 2021, were combined for an overall 22-week study period. During the study period, 15,254 facilities sent 330,864 weekly reports with case counts to NHSN; of these, 15,236 facilities (99.9%) sent 144,334 (43.6%) weekly reports with counts of residents by vaccination status.

A generalized linear mixed effects model was used with a zero-inflated Poisson distribution (used to model data that have an excess of zero counts) for case counts by vaccination status, offset by resident counts, to estimate the ratio of infection rates among fully vaccinated and unvaccinated residents. To account for variability across sites, facility was included as a random effect. Because of potential for confounding by time, calendar week was modeled as a fixed effect covariate. Nonlinearity of infection rates over calendar weeks was modeled with cubic splines. To evaluate the effect of circulating SARS-CoV-2 variants on VE, the study period was stratified into three periods: 1) pre-Delta (March 1–May 9); 2) intermediate, the period when Delta circulation was documented but not predominant (May 10–June 20); and 3) Delta, when ≥50% of SARS-CoV-2 viruses sequenced were the Delta variant (June 21–August 1), with an interaction term between this categorical time variable and vaccination status to obtain VE estimates for each period. The following characteristics were evaluated as potential confounders of VE: 1) facility-level cumulative SARS-CoV-2 infection rates combined for staff members and residents from May 8, 2020, through the week of reporting; 2) weekly local county incidence of SARS-CoV-2 infections; and 3) CDC Social Vulnerability Index score** for each facility’s county. The change-in-estimate criterion for the regression coefficient with a 10% cutoff was used to evaluate covariates; none met this criterion. VE was estimated as 1 minus the rate ratio multiplied by 100, adjusted for calendar week and facility as a random effect. VE for the “other” category is not presented because this group combines different categories, and estimates would not be meaningful. Data analysis was conducted using SAS (version 9.4; SAS Institute) and R (version 4.0.4; R Foundation); statistical significance was defined as p<0.05. This activity was reviewed by CDC and was conducted consistent with federal laws and institutional policies.††

After applying exclusion criteria and combining facility-level weekly case and corresponding resident counts, the analysis included 136,160 reports from 14,997 facilities (median of eight reports per facility; interquartile range = 6–10), with 3,862 (25.8%) facilities reporting during the pre-Delta period, 11,581 (77.2%) during the intermediate period, and 14,917 (99.5%) during the Delta period. Overall, the analysis included 10,428,783 aggregate weekly resident counts, including 1,531,446 (14.7%) unvaccinated residents, 5,174,098 (49.6%) fully vaccinated with Pfizer-BioNTech, 2,633,700 (25.3%) fully vaccinated with Moderna, and 1,089,539 (10.4%) with “other” vaccination status. Overall, 6,879 COVID-19 cases were identified, including 2,113 (30.7%) in unvaccinated residents, 2,603 (37.8%) in residents fully vaccinated with Pfizer-BioNTech, 1,302 (18.9%) in residents fully vaccinated with Moderna, and 861 (12.5%) in residents with “other” vaccination status.

During the pre-Delta period, adjusted VE against infection among those fully vaccinated (versus unvaccinated) was 74.7% for any mRNA vaccine, 74.2% for Pfizer-BioNTech, and 74.7% for Moderna (Table). During the Delta period, adjusted VE against infection among those fully vaccinated was 53.1% for any mRNA vaccine, 52.4% for Pfizer-BioNTech, and 50.6% for Moderna. VE estimates for the Delta period were significantly lower than those for the pre-Delta period (p<0.001). VE point estimates during the intermediate period were lower than those during the pre-Delta period; however, the estimates were not significantly different (p = 0.06) (Table).

Discussion
Analysis of nursing home COVID-19 data from NHSN indicated a significant decline in effectiveness of full mRNA COVID-19 vaccination against laboratory-confirmed SARS-CoV-2 infection, from 74.7% during the pre-Delta period (March 1–May 9, 2021) to 53.1% during the period when the Delta variant predominated in the United States. This study could not differentiate the independent impact of the Delta variant from other factors, such as potential waning of vaccine-induced immunity. Further research on the possible impact of both factors on VE among nursing home residents is warranted. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multipronged COVID-19 prevention strategies, including infection control,§§ testing, and vaccination of nursing home staff members, residents, and visitors are critical.

These results (pre-Delta 74.7%; Delta 53.1%) fall within the range of findings from other studies of COVID-19 mRNA VE in nursing home residents conducted before the Delta variant was prevalent, with estimates against infection ranging from 53% to 92% (3–6). Variability in VE estimates across studies can result from differences in underlying populations, SARS-CoV-2 testing practices and diagnostics, prevalence of previous infections, analytic methods, and virus variant strains in circulation.

Nursing home residents, who are often elderly and frail, might have a less robust response to vaccines, and are at higher risk for infection with SARS-CoV-2 and for severe COVID-19 (8). In addition, nursing home residents were among the earliest groups vaccinated in the United States; thus, if vaccine-induced immunity does wane over time, this decrease in VE might first be observed among nursing home residents. Because increased U.S. circulation of the Delta variant coincided with a period ≥6 months after vaccine introduction, the extent to which reduced vaccine protection against Delta and potential waning immunity contributed to the lower VE in the Delta period could not be determined by this study.

Nursing homes were aggressive in case ascertainment because of guidelines recommending weekly point prevalence surveys if a single SARS-CoV-2 infection in a staff member or resident was identified.¶¶ This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic infections. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time.

The findings in this report are subject to at least five limitations. First, resident-level demographic or clinical data were not reported to NHSN. Therefore, the analysis could not control for potential confounders, such as age, presence of underlying health conditions, or the influence of previous SARS-CoV-2 infections on VE. Second, vaccination dates were not available and time since vaccination could not be measured to evaluate potential waning of protection. Third, staff member vaccination data were not sufficiently complete to assess as a potential confounder. Fourth, before June 7, 2021, weekly reporting of resident vaccination status was voluntary, and missing data limited inclusion of facility records during this period. Although the magnitude of potential bias introduced by missing data could not be assessed, a bias indicator analysis was conducted, which indicated that VE was likely underestimated during the pre-Delta period (COVID-19 Vaccine Effectiveness Team, CDC, unpublished data, 2021). Finally, the study assessed only nursing home residents and is not generalizable to the broader population.

Both Pfizer-BioNTech and Moderna mRNA vaccines were highly effective in preventing SARS-CoV-2 infection in nursing home residents early after vaccine introduction. However, the effectiveness among this population in recent months has been significantly lower. To prevent transmission of SARS-CoV-2 in nursing homes, these findings highlight the critical importance of COVID-19 vaccination of staff members, residents, and visitors and adherence to rigorous COVID-19 prevention strategies. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence

Abstract
Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). However, in July, the effectiveness against infection was considerably lower for mRNA-1273 (76%, 95% CI: 58-87%) with an even more pronounced reduction in effectiveness for BNT162b2 (42%, 95% CI: 13-62%). Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.

Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection
Among Frontline Workers Before and During B.1.617.2 (Delta) Variant
Predominance — Eight U.S. Locations, December 2020–August 2021

During December 14, 2020–April 10, 2021, data from the HEROES-RECOVER Cohorts,* a network of prospective cohorts among frontline workers, showed that the PfizerBioNTech and Moderna mRNA COVID-19 vaccines were approximately 90% effective in preventing symptomatic and asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19, in real-world conditions (1,2). This report updates vaccine effectiveness (VE) estimates including all COVID-19 vaccines available through August 14, 2021, and examines whether VE differs for adults with increasing time since completion of all recommended vaccine doses. VE before and during SARS-CoV-2 B.1.617.2 (Delta) variant predominance, which coincided with an increase in reported COVID-19 vaccine breakthrough infections, were compared (3,4).

Methods for the HEROES-RECOVER Cohorts have been published previously (1,2,5). Health care personnel, first responders, and other essential and frontline workers in eight U.S. locations across six states were tested weekly for SARS-CoV-2 infection by reverse transcription–polymerase chain reaction (RT-PCR)† and upon the onset of any COVID-19–like illness. Weeks when the Delta variant accounted for ≥50% of viruses sequenced, based on data from each respective location, were defined as weeks of Delta variant predominance. Vaccination was documented by self-report and verified by provision of vaccine cards or extraction from electronic medical records or state immunization registries. Among 4,217 participants, 3,483 (83%) were vaccinated; 2,278 (65%) received Pfizer-BioNTech, 1,138 (33%) Moderna, and 67 (2%) Janssen (Johnson & Johnson) COVID-19 vaccines. Cox proportional hazards models were used to calculate ratios of unvaccinated to fully vaccinated (≥14 days after receipt of all recommended COVID-19 vaccine doses) infection rates, adjusted for occupation, site, and local viral circulation (6), and weighted for inverse probability of vaccination using sociodemographic characteristics, health information, frequency of close social contact, and mask use. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.

During the 35-week study period, 4,136 participants with no previous laboratory-documented SARS-CoV-2 infection contributed a median of 20 unvaccinated days per participant (interquartile range [IQR] = 8–45 days; total = 181,357 days), during which 194 SARS-CoV-2 infections were identified;
89.7% of these infections were symptomatic. A total of 2,976 participants contributed a median of 177 fully vaccinated days (IQR = 115–195 days; total = 455,175 days) with 34 infections, 80.6% of which were symptomatic. Adjusted VE against SARS-CoV-2 infection was 80% (95% confidence interval [CI] = 69%–88%). The VE point estimate was 85% among participants for whom <120 days had elapsed since completion of full vaccination compared with 73% among those for whom ≥150 days had elapsed; however the VE 95% CI were overlapping, indicating the difference was not statistically significant (Table).


During Delta variant–predominant weeks at study sites, 488 unvaccinated participants contributed a median of 43 days (IQR = 37–69 days; total = 24,871 days) with 19 SARS-CoV-2 infections (94.7% symptomatic); 2,352 fully vaccinated participants contributed a median of 49 days (IQR = 35–56 days; total = 119,218 days) with 24 SARS-CoV-2 infections (75.0% symptomatic). Adjusted VE during this Delta predominant period was 66% (95% CI = 26%–84%) compared with 91% (95% CI = 81%–96%) during the months preceding Delta predominance. During December 14, 2020–August 14, 2021, full vaccination with COVID-19 vaccines was 80% effective in preventing RT-PCR–confirmed SARS-CoV-2 infection among frontline workers, further affirming the highly protective benefit of full vaccination up to and through the most recent summer U.S. COVID-19 pandemic waves. The VE point estimates declined from 91% before predominance of the SARS-CoV-2 Delta variant to 66% since the SARS-CoV-2 Delta variant became predominant at the HEROES-RECOVER cohort study sites; however, this trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants. As with all observational VE studies, unmeasured and residual confounding might be present. Active surveillance through the cohort is ongoing and VE estimates will be monitored continuously. Although these interim findings suggest a moderate reduction in the effectiveness of COVID-19 vaccines in preventing infection, the sustained two thirds reduction in infection risk underscores the continued importance and benefits of COVID-19 vaccination.