Scientific data is clear that vaccines are effective at preventing severe illness, hospitalization, and death from Covid-19, including with the Delta variant, and that booster doses likely provide additional protection.

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  • Protection of full vaccination against hospitalization/death remains significant. Pfizer vaccine efficacy against symptomatic disease from the Delta variant (Bernal et al., NEJM, July 21, 2021):

    • 88.0% effective after two doses (95%CI 85.3 to 90.1%)

    • 30.7% effective after one dose (95%CI 25.2 to 35.7%)

  • Griffin, Haddix, et al., “SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status — Los Angeles County, California, May 1–July 25, 2021,” MMWR, Aug 24, 2021, link. This study reports on Covid testing data from LA County, analyzed by vaccination status (fully, partially, not) (n=43,127 individuals with positive Covid test).

    • 25.3% of positive tests were in fully vaccinated individuals, 3.3% partially vaccinated, 71.4% in unvaccinated.

    • Lower percentages of fully vaccinated individuals were hospitalized (3.2% vs 6.2%), admitted to ICU (0.5% vs 1.0%), and required mechanical ventilation (0.2% vs 0.3%) compared to partially vaccinated persons (statistically significant differences).

    • On July 25, infection rate among unvaccinated individuals was 4.9 times higher and hospitalization rate was 29.2 times higher than among fully vaccinated persons.

    • Percentage of sequences due to Delta increased from 0% to a significant majority (87-91%) from May 1 to July 25.

    • In May there were differences in median Ct values between vaccinated and unvaccinated individuals (cycle threshold values, measure of viral load). By July, no differences were noted based on vaccination status.

    • Among fully vaccinated persons on July 25, 55.2% had received the Pfizer-BioNTech vaccine, 28.0% had received the Moderna vaccine, and 16.8% had received the Janssen vaccine.

    • Median age was higher among vaccinated persons who were hospitalized or admitted to ICU compared to partially and unvaccinated persons. For hospitalization: median 64 years vs 59 years and 49 years, respectively. For ICU admission: 64 years vs 65 and 56 years, respectively.

  • Havers, Pham, et al., “COVID-19-associated hospitalizations among vaccinated and unvaccinated adults ≥18 years – COVID-NET, 13 states, January 1 – July 24, 2021,” medRxiv, Aug 29, 2021, link. Pre-print from the CDC reporting on COVID-NET surveillance data looking at breakthrough Covid cases in fully vaccinated individuals leading to hospitalization and death between Jan 1 and June 30, 2020. Hospitalized fully vaccinated Covid cases were older compared to hospitalized unvaccinated Covid cases (73 vs 59 yrs), more likely to have 3 or more underlying medical conditions (70.8% vs 56.1%), and be residents of long-term care facilities (14.5% vs 5.5%). Cumulative hospitalization rates between Jan 1 and July 24, 2021 were 17 times higher among unvaccinated persons compared to vaccinated persons. Between June 27 and July 24, 2021 (when Delta was dominant), hospitalization rates were more than 10 times higher for unvaccinated compared to vaccinated persons.

  • Scobie, Johnson, et al., “Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status — 13 U.S. Jurisdictions, April 4–July 17, 2021,” MMWR, Sept 10, 2021, link. Study published by the CDC reporting on vaccination efficacy data during Delta dominance period (June 20-July 17) compared to pre-Delta (April 4-June 19). Incidence rate ratios comparing vaccine effectiveness among fully vaccinated vs not vaccinated individuals did not change significantly for hospitalizations and death before to after Delta dominance (13.3 to 10.4 and 16.6 to 11.3 respectively), but overall cases did decrease from 11.1 to 4.6. Fully vaccinated people had 5x lower risk of infection, more than 10 times reduced risk of hospitalization and death during Delta dominance period.

  • Grannis, Rowley, et al., “Interim Estimates of COVID-19 Vaccine Effectiveness Against COVID-19–Associated Emergency Department or Urgent Care Clinic Encounters and Hospitalizations Among Adults During SARS-CoV-2 B.1.617.2 (Delta) Variant Predominance — Nine States, June–August 2021,” MMWR, Sept 10, 2021, link. Study reporting on vaccine effectiveness during period of Delta dominance in the US. Vaccine effectiveness: 86% against hospitalization (95%CI 82-89%), significantly lower among 75+ yrs vs 18-74 yrs (76% vs 89%); 82% against emergency/urgent care encounters (95%CI 81-84%).

  • Bajema, Dahl, et al., “Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalization — Five Veterans Affairs Medical Centers, United States, February 1–August 6, 2021,” MMWR, Sept 10, 2021, link. Study reporting on vaccine effectiveness data from Veterans Affairs Medical Centers, Feb 1-Aug 6, 2021. During period of Delta variant circulation, effectiveness against hospitalization remained high (86.8% effective for entire study period; 89.3% for Delta period July 1-Aug 6). Effectiveness was lower for persons aged 65+ compared to 18-64 yrs (79.8% vs 95.1%). No difference was found between persons completing fully vaccination less than 90 days before positive test vs 90+ days.

Data indicating that vaccines may be less effective at preventing infection overall than at preventing severe illness, hospitalization, and death with the Delta variant. Fully vaccinated individuals who become infected can transmit the virus, reportedly have similar viral loads to unvaccinated individuals, and can experience persistent symptoms (long Covid).

  • Higher rates of breakthrough infection with Delta variant compared to previous variants.

    • Frontline workers cohort tested weekly: Pre-Delta 91% effective vs Delta-dominant 66% against infection (Fowlkes et al., MMWR Aug 2021).

    • Nursing home residents tested weekly or biweekly: Pre-Delta 74.7% effective, Intermediate 67.5% effective, Delta 53.1% effective (Nanduri et al., MMWR, Aug 18, 2021).

  • Pre-print from the Mayo Clinic reporting on cohort of about 25,000 vaccinated and unvaccinated individuals in Minnesota, Jan to July 2021. Analyzing vaccine effectiveness monthly, they found a significant decrease in July compared to previous months (76% for moderna, 95%CI 58-87%; 42% for Pfizer, 95%CI 13-62%). Effectiveness against hospitalization remained high in the month of July. Puranik, Lenehan, et al., “Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence,” medRxiv, Aug 9, 2021, link.

    • Breakthrough infection rates were consistently lower (when looking at data from MN and other states) for those fully vaccinated with Moderna compared to Pfizer. Hospitalization rates with breakthrough cases for Moderna vaccinated were about half the rates for those Pfizer vaccinated (ICU admission and death rates were not significantly different).

    • Note that several authors of this pre-print work for nference, which is collaborating with Moderna, Pfizer, and Janssen and have ties to other pharmaceutical companies. The Mayo Clinic may stand to gain financially from this research.

    • Axios reported that this pre-print may be part of Biden Admin’s calculation on booster shots https://www.axios.com/coronavirus-vaccines-pfizer-moderna-delta-biden-e9be4bb0-3d10-4f56-8054-5410be357070.html

  • Fowlkes, Gaglani, et al., “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,” MMWR Aug 24, 2021, link. This study provides an update on the HEROES vaccine effectiveness cohort of health care and other frontline workers that has been previously reported on. This report provides an update through Aug 14, 2021.

    • Calculated vaccine effectiveness against SARS-CoV-2 infection was 80% (95%CI 69-88%) during the 35-week study period.

    • Vaccine effectiveness was 85% among participants for whom <120 days had elapsed since full vaccination. Vaccine effectiveness was 73% among those for whom 150 or more days had elapsed since full vaccination. This difference was NOT statistically significant.

    • Looking just at the weeks where Delta was dominant at the location (Delta accounted for 50 or more % of samples sequenced, not reported whether for county or state or region), vaccine effectiveness was 66% (95%CI 26-84%) vs 91% (95%CI 81-96%) in the pre-delta dominance period.

    • The authors note: “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.”

  • Gounder, Saint, et al., “COVID-19 Outbreak Among Vaccinated Staff and Residents at a Skilled Nursing Facility in Los Angeles County,” Infection Control & Hospital Epidemiology, Sept 21, 2021, link. Report of an outbreak in a skilled nursing facility in Los Angeles that most likely began with a fully vaccinated health care worker who became infected and was asymptomatic, leading to infections of other staff and residents, many of whom were vaccinated. The facility had high vaccination rates among both residents and staff. This study underlines the importance of continued comprehensive infection control measures, in addition to vaccination, including weekly surveillance testing to identify and isolate cases.

  • Viral loads similar between vaccinated and unvaccinated (Brown et al., MMWR, July 30, 2021; Riemersma et al., medRxiv, Aug 11, 2021).

  • Transmission from asymptomatic vaccinated patient to other vaccinated patients and health care workers in inpatient hospital ward (Linsenmeyer et al., medRxiv, Aug 10, 2021).

  • Study from Israel of breakthrough infections among health care workers found 19% of infected vaccinated health care workers experienced symptoms longer than 6 weeks (Bergwerk et al., NEJM, July 28, 2021).

Data indicating that mRNA vaccine protection, especially the Pfizer mRNA vaccine, may wane months after vaccination, around 4-5 months after the second dose.

  • Cohort study from Israel (pre-print) looking at fully vaccinated adults who tested positive for SARS-CoV-2 at least 2 weeks after the second dose, between May 15 and July 26, 2021. Almost 34,000 fully vaccinated adults received a PCR test during the study period. 1.8% of patients had a positive result. Significantly higher rate of positivity among individuals who received second dose at least 146 days (4-5 months) prior to the PCR test compared to individuals who received the second dose more recently. For individuals over 60 years, odds for infection was 3.00 (95%CI 1.86-5.11), 40-59 years odds for infection was 2.29 (95%CI  1.67-3.17), 18-39 years odds for infection was 1.74 (95%CI 1.27-2.37). Israel, Merzon, et al., “Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort,” medRxiv, Aug 5, 2021, link.

  • Pre-print from Israel reporting on data from an HMO. Found that odds of infection were higher the longer the time interval from vaccination to infection. Comparing early vaccinees (Jan-Feb) to late vaccinees (March-April), odds of infection was 1.53 times higher overall (95%CI 1.40-1.68) between June 1 and July 27, 2021. Mizrahi, Lotan, et al., “Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Preliminary Study,” medRxiv, July 31, 2021, link.

  • Large community surveillance study from the UK where random households are tested at pre-determined intervals found that 2 doses of Pfizer mRNA covid vaccine reduces the risk of new SARS-CoV-2 infections. Protection waned, becoming similar to Astra Zeneca protection at 4-5 months. No evidence of difference in effectiveness with intervals <9 or 9+ weeks between 2 doses. Protection against infection was larger for those vaccinated with prior infection than those vaccinated without prior infection. Ct values were similar with Delta variant between vaccinated and unvaccinated. Pouwells, Pritchard, et al., “Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK,” pre-print posted by Univ of Oxford, link.

  • Fowlkes, Gaglani, et al., “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,” MMWR Aug 24, 2021, link. This study provides an update on the HEROES vaccine effectiveness cohort of health care and other frontline workers that has been previously reported on. This report provides an update through Aug 14, 2021.

    • Calculated vaccine effectiveness against SARS-CoV-2 infection was 80% (95%CI 69-88%) during the 35-week study period.

    • Vaccine effectiveness was 85% among participants for whom <120 days had elapsed since full vaccination. Vaccine effectiveness was 73% among those for whom 150 or more days had elapsed since full vaccination. This difference was NOT statistically significant.

    • Looking just at the weeks where Delta was dominant at the location (Delta accounted for 50 or more % of samples sequenced, not reported whether for county or state or region), vaccine effectiveness was 66% (95%CI 26-84%) vs 91% (95%CI 81-96%) in the pre-delta dominance period.

    • The authors note: “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.”

  • Levine-Tiefenbrun, Yelin, et al., “Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine,” medRxiv, Sept 1, 2021, link. Pre-print reporting on more data from Israel about breakthrough infections following the second mRNA (Pfizer) vaccine dose in adults above 20 yrs between June 28 and Aug 24 when Delta was dominant in Israel. They looked at viral loads in patients who tested positive 7 or more days following the second vaccine dose as well as patients who tested positive less than 7 days after a booster (third) dose (n=11,889). They found that the vaccine was effective in resulting viral load with a Delta variant infection post-second dose vaccination by 15-fold over the first 2 months following vaccination. But the effectiveness in viral load reduction is reduced over time post vaccination, significantly decreasing over 3 months and effectively vanishing at about 6 months post vaccination. This helps explain the multiple studies finding no difference in viral load between vaccinated and unvaccinated individuals infected with the Delta variant. Additionally, these results suggest that the decrease in vaccine effectiveness is related to waning immunity over time since vaccination, rather than inherent capacity of the Delta variant. After a third (booster) dose, viral load was decreased significantly again.

  • Keehner, Horton, et al., “Resurgence of SARS-CoV-2 Infection in a Highly Vaccinated Health System Workforce,” NEJM, Sept 1, 2021, link. This short report presents data from UC San Diego, which experienced a resurgence in HCW infections in June 2021. By March 2021, 76% of the workforce was fully vaccinated, up to 83% by July. Infections had decreased significantly by Feb 2021 and remained low through June. Infections began rising quickly following June 15 revocation of California’s mask order and increased spread of the Delta variant. Between March 1 and July 31,  227 HCWs tested positive, with 57.3% fully vaccinated. Of those fully vaccinated, 83.8% were symptomatic. No deaths were reported among vaccinated or unvaccinated workers and only 1 unvaccinated worker was hospitalized. Vaccine effective was 90% in March and dropped to 65.5% in July (95%CI 48.9- 76.9%). In workers completing vaccination in Jan or Feb, the attack rate was 6.7 per 1000 persons vs those completing vaccination in March thru May it was 3.7 per 1000 persons. Among unvaccinated individuals, the attack rate in July was 16.4 per 1000 persons. “Our findings underline the importance of rapidly reinstating nonpharmaceutical interventions, such as indoor masking and intensive testing strategies, in addition to continued efforts to increase vaccinations, as strategies to prevent avoidable illness and deaths and to avoid mass disruptions to society during the spread of this formidable variant.”

  • Goldberg, Mandel, et al., “Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel,” medRxiv, Aug 30, 2021, link. Pre-print posted by the Israel MOH reporting on data showing reduced effectiveness of vaccines over time. Look at data from Israel’s centralized health care system, they found that the rate of documented SARS-CoV-2 infections increased as a function of time. For certain subgroups, specifically adults 60 yrs or older, protection against severe disease also decreased over time.

Data  indicating that a third dose of mRNA vaccines, especially with the Pfizer vaccine, provides improved protection.

  • Bar-On, Goldberg, et al., “Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel,” NEJM, Sept 15, 2021. This study reported on effectiveness of booster doses among those 60 years of age and older in Israel- at least 12 days following a booster dose (Pfizer), rate of confirmed infection was 11 times lower in the booster group and rate of severe illness was 19.5 times lower in the booster group compared to the nonbooster group (only 2 doses).

  • “Pfizer and BioNTech Announce Submission of Initial Data to U.S. FDA to Support Booster Dose of COVID-19 Vaccine” Aug 16, 2021, https://www.businesswire.com/news/home/20210816005494/en/.

    • Phase 1 safety and immunogenicity data in individuals who received a third dose of the Pfizer-BioNTech vaccine (BNT162b2) show a favorable safety profile and robust immune responses

    • The booster dose elicited significantly higher neutralizing antibody titers against the initial SARS-CoV-2 virus (wild type), and the Beta and Delta variants, compared to the levels observed after the two-dose primary series

    • After the booster dose, neutralizing titers for variants were similar to wild type

    • Given the high levels of immune responses observed, a booster dose given within 6 to 12 months after the primary vaccination schedule may help maintain a high level of protection against COVID-19

  • Gilbert et al., “Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial,” medRxiv, August 15, 2021, link.

    • Preprint funded by Moderna

    • Researchers looked for biomarkers in vaccinated individuals infected with SARS-CoV-2 and those with no evidence of previous SARS-2 infection. Participants were part of Moderna’s Covid vaccine clinical trial.

    • Participants were selected for measurement of 4 serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike RBD, and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers.

    • Day 29 and Day 57 marker correlates analyses excluded participants with any evidence of SARS-CoV-2 infection before 7 days post Day 29 and Day 57 visit, respectively, because natural infection before the serology may have modulated the antibody response.

    • All 4 antibody markers at Day 29 and at Day 57 were inversely correlated with the risk of Covid-19 occurrence through 3 – 4 months post second dose.

    • For breakthrough symptomatic infections, VE was 50.8% (−51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%) at 4 months post second dose.

    • Almost all infections were similar to wild-type (i.e., not Delta), so authors could not assess the robustness of correlates to SARS-CoV-2 VOCs.

  • Pre-print reporting on data from Maccabi health services (HMO, Israel)- note conflicts of interest reported by authors-

    • “We found that 7-13 days after the booster shot there is a 48-68% reduction in the odds of testing positive for SARS-CoV-2 infection and that 14-20 days after the booster the marginal effectiveness increases to 70-84%. Further studies are needed to determine the duration of protection conferred by the third dose and its effect on severe disease.” https://www.medrxiv.org/content/10.1101/2021.08.29.21262792v1

  • Levine-Tiefenbrun, Yelin, et al., “Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine,” medRxiv, Sept 1, 2021, link. Pre-print reporting on more data from Israel about breakthrough infections following the second mRNA (Pfizer) vaccine dose in adults above 20 yrs between June 28 and Aug 24 when Delta was dominant in Israel. They looked at viral loads in patients who tested positive 7 or more days following the second vaccine dose as well as patients who tested positive less than 7 days after a booster (third) dose (n=11,889). They found that the vaccine was effective in resulting viral load with a Delta variant infection post-second dose vaccination by 15-fold over the first 2 months following vaccination. But the effectiveness in viral load reduction is reduced over time post vaccination, significantly decreasing over 3 months and effectively vanishing at about 6 months post vaccination. This helps explain the multiple studies finding no difference in viral load between vaccinated and unvaccinated individuals infected with the Delta variant. Additionally, these results suggest that the decrease in vaccine effectiveness is related to waning immunity over time since vaccination, rather than inherent capacity of the Delta variant. After a third (booster) dose, viral load was decreased significantly again.