Editor’s Note: These letters were published on November 10, 2021, at NEJM.org.

Correspondence

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

To the Editor

In their study, Lopez Bernal et al. (Aug. 12 issue)1 estimate the effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against symptomatic disease caused by the B.1.617.2 (delta) variant. The authors encountered a unique situation and were able to capitalize on it. The decision in the United Kingdom to use an extended administration interval of up to 12 weeks allowed partially vaccinated and fully vaccinated populations to be studied. I found the test-negative case–control analysis to be reassuring. The findings show that the BNT162b2 vaccine was more effective than the ChAdOx1 nCoV-19 vaccine, and both vaccines were less effective against the delta variant than against the B.1.1.7 (alpha) variant. I believe that the values for efficacy will widen further with the waning of vaccine immunity.

The alpha and delta variants differ according to an amino acid at P681; in the delta variant, the arginine substitution at this position gives it a major replicative advantage. After vaccination with the messenger RNA vaccines, the serum levels of IgG and IgA rise promptly, but the IgA level falls more quickly and to a lower level than the IgG level.2 At present, we are fortunate that the vaccines developed for the alpha variant afford some protection against severe disease from the delta variant, but we need vaccines against specific variants to reduce mortality and the prevalence of asymptomatic nasal carriage. We also need specific vaccines that produce a strong soluble IgA immune response in the nasopharynx.

Josh Torgovnick, M.D.
Mount Sinai Hospital, New York, NY

No potential conflict of interest relevant to this letter was reported.

This letter was published on November 10, 2021, at NEJM.org.

  1. 1. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (delta) variant. N Engl J Med 2021;385:585-594.

  2. 2. Wisnewski AV, Campillo Luna J, Redlich CA. Human IgG and IgA responses to COVID-19 mRNA vaccines. PLoS One 2021;16(6):e0249499-e0249499.

To the Editor

Lopez Bernal et al. show that vaccine effectiveness against symptomatic infection with the delta variant of SARS-CoV-2 is preserved. Recent reports indicate that vaccination is less protective against asymptomatic community transmission of the delta variant than against that of earlier variants.1,2 Here, we report cryptic transmission of the delta variant between vaccinated inpatients.

Transmission of SARS-CoV-2 Infection among Vaccinated Persons with Exposure in a Single Inpatient Ward.

Shown is a diagram of the transmission of SARS-CoV-2 infections across time among persons with exposure in one of three inpatient rooms. The teal bars indicate the number of days spent in a room. The rows of small rectangles under “Room Location” show the location of the room where the infected person or persons had stayed (red rectangle), relative to the adjacent rooms (white rectangles) on either side of the hallway (the space between the rows); the small, gray rectangles within the rooms represent the number of beds. The numbers in the orange circles indicate the polymerase-chain-reaction cycle-threshold value in the person who had a positive PCR test. An asterisk in a green circle indicates a negative antigen test. The first patient who received a diagnosis is designated as the index patient.

At the end of a 24-day admission, a vaccinated patient in a private room received a diagnosis of asymptomatic infection with the delta variant after routine predischarge testing (index patient). Contact tracing of 38 patients, 168 staff members, and 6 visitors led to the detection of symptomatic infection in 1 vaccinated, nearby patient and asymptomatic infection in 3 vaccinated, nearby patients, 1 vaccinated visitor, and 1 vaccinated employee who had provided care for the undiagnosed, infected index patient (Figure 1). Patients were unmasked, whereas staff wore surgical masks. Polymerase-chain-reaction cycle threshold values for breakthrough infections at the Veterans Affairs Boston Healthcare System between March 11 and July 31, 2021, showed that the viral load for the delta variant was more than 1000 times as high as for earlier variants (mean [±SD] cycle thresholds of 21.7±4.3 among 15 persons with the delta variant and 31.8±10.9 among 12 persons with earlier variants; P=0.003 by the t-test).1,2 These findings show that the delta variant is transmitted between vaccinated inpatients with a high viral load and highlight the continued efficacy of masking and vaccination for the protection of health care personnel and the potential need for postadmission surveillance to prevent cryptic transmission of the delta variant.

Katherine Linsenmeyer, M.D.
Kalpana Gupta, M.D., M.P.H.
Michael E. Charness, M.D.
Veterans Affairs Boston Healthcare System, West Roxbury, MA

Dr. Gupta reports having equity in Moderna Pharmaceuticals and Abbott. No other potential conflict of interest relevant to this letter was reported.

This letter was published on November 10, 2021, at NEJM.org.

  1. 1. Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings — Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep 2021;70:1059-1062.

  2. 2. Li B, Deng A, Li K, et al. Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 delta variant. July 23, 2021 (https://www.medrxiv.org/content/10.1101/2021.07.07.21260122v2). preprint.

To the Editor

Distribution of Cases, Hospitalizations, and Deaths Related to the Delta Variant of SAR-CoV-2 among All Age Groups.

Lopez Bernal et al. present an incomplete picture of the Covid-19 vaccine effectiveness against the delta variant. In the technical briefing by Public Health England, dated July 23, 2021, it was reported that 90.2% of total deaths (415 of 460 persons) and 37.0% of hospitalizations (1365 of 3692 persons) occurred among adults 50 years of age older, who constitute approximately 40% of the U.K. population (Table 1).1,2 Of the hospitalizations in this age group, 51.5% occurred in fully vaccinated adults, 14.0% in partially vaccinated adults, and 32.2% in unvaccinated adults. Most importantly, of the deaths that occurred in this age group, 53.0% (220 persons) occurred in fully vaccinated adults and 31.6% (131 persons) in unvaccinated adults. These data suggest that a considerable proportion of the vaccinated population of adults 50 years of age or older who are infected with SARS-CoV-2 are at substantial risk for harm, including hospitalization and death. We believe that it is most important to take immediate remedial measures to protect lives among older adults at high risk through a balanced public disclosure of all the data from the recent briefing by Public Health England.

Venkata R. Emani, M.D.
Central Valley Cardiovascular Associates, Manteca, CA

Raghunath Reddy, M.D.
Stockton Primary Care, Stockton, CA

Sanjeev Goswami, M.D.
San Joaquin Critical Care Medical Group, Stockton, CA

No potential conflict of interest relevant to this letter was reported.

This letter was published on November 10, 2021, at NEJM.org.

  1. 1. Public Health England. SARS-CoV-2 variants of concern and variants under investigation in England: technical briefing 19. July 23, 2021 (https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1005517/Technical_Briefing_19.pdf).

  2. 2. Population pyramids of the world from 1950 to 2100 — UK population, 2020 (https://www.populationpyramid.net/united-kingdom/2020/).

Response

The authors reply: We agree with the points raised by Torgovnick regarding the differences in effectiveness between the two vaccines studied. We continue to see differences, although it is important to recognize that the demographic and clinical characteristics of the populations that received BNT162b2 differ from those of the populations that received ChAdOx1 nCoV-19 in the United Kingdom. As third doses are now being implemented in several countries, we agree that boosting with vaccines against specific variants of SARS-CoV-2 should be considered.

Linsenmeyer et al. report a transmission event. Recent data on the delta variant and on waning immunity indicate that protection against infection is lower than protection against severe disease.1,2 Therefore, as has been seen, vaccine recipients could become infected with the delta variant and transmit the infection to others. Nevertheless, protection against severe disease, in particular, appears to be well maintained.3

Emani et al. comment on reported cases, hospitalizations, and deaths among vaccinated persons in England. The incidence of hospitalization and mortality in vaccine-eligible cohorts in England are significantly lower than during the waves of infection before the availability of a vaccine, despite a large increase in cases with the emergence of the delta variant.4 Data on cases, hospitalizations, and deaths according to vaccination status in England are published on a weekly basis.5 One would expect that the incidence of hospitalization and mortality among vaccinated persons is increasing relative to unvaccinated persons simply because vaccine coverage is increasing. Even with a highly effective vaccine, as more and more people are vaccinated there will be an increasing proportion of deaths among vaccinated people. To take an extreme example, if everyone in the population is vaccinated, all deaths will occur among vaccinated persons (even if the vaccine is 99% effective at preventing deaths).

Jamie Lopez Bernal, F.F.P.H., Ph.D.
Charlotte Gower, D.Phil.
Nick Andrews, Ph.D.
Public Health England, London, United Kingdom

for the Public Health England Delta Variant Vaccine Effectiveness Study Group

Since publication of their article, the authors report no further potential conflict of interest.

This letter was published on November 10, 2021, at NEJM.org.

  1. 1. Pouwels KB, Pritchard E, Matthews PC, et al. Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nat Med 2021 October 14 (Epub ahead of print).

  2. 2. Chemaitelly H, Tang P, Hasan MR, et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med 2021;385:e83-e83.

  3. 3. Sheikh A, McMenamin J, Taylor B, Robertson C; the EAVE II Collaborators. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397:2461-2462.

  4. 4. Public Health England. National flu and COVID-19 surveillance reports. October 8, 2020 (https://www.gov.uk/government/statistics/national-flu-and-covid-19-surveillance-reports).

  5. 5. Public Health England. COVID-19 vaccine surveillance reports (weeks 19 to 38). May 14, 2021 (https://www.gov.uk/government/publications/covid-19-vaccine-surveillance-report).

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