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To the Editor

In the article by Dagan et al. (April 15 issue),1 the effectiveness of the BNT162b2 mRNA vaccine against coronavirus disease 2019 (Covid-19) in a real-world setting is presented. This study is important in the battle against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We note that recipients of a solid-organ transplant are at increased risk for severe SARS-CoV-2 infection2,3 and that transplant recipients have typically been excluded from trials investigating Covid-19 vaccines.4 In the study by Dagan et al., 2804 solid-organ recipients were included, of whom 435 were matched to unvaccinated controls.

We would like the authors to provide more information about these patients. What types of solid-organ transplants were included? What was the vaccine effectiveness among these patients? How many, and what kinds of, adverse events occurred? What was the immune response? We believe that such information could help clarify the safety and effectiveness of this vaccine in recipients of solid-organ transplants.

Stefan Roest, M.D.
Rogier A.S. Hoek, M.D.
Olivier C. Manintveld, M.D., Ph.D.
Erasmus MC Transplant Institute, Rotterdam, the Netherlands

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

This letter was published on April 21, 2021, at NEJM.org.

  1. 1. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:14121423.

  2. 2. Centers for Disease Control and Prevention. People with certain medical conditions. March 8, 2021 (www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html).

  3. 3. Aziz F, Mandelbrot D, Singh T, et al. Early report on published outcomes in kidney transplant recipients compared to nontransplant patients infected with coronavirus disease 2019. Transplant Proc 2020;52:26592662.

  4. 4. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:26032615.

Response

The authors reply: Roest et al. request a subgroup analysis involving the solid-organ recipients in our study. We have received multiple inquiries requesting vaccine-effectiveness measures in specific subgroups of patients. In response to these requests, we have performed a number of additional subgroup analyses, each time restricting the matching process to persons with a specific condition of interest, in order to maximize the sample size.

Estimated Vaccine Effectiveness in Subgroups.

We also extended the follow-up period through February 14, 2021. The extended analysis included almost 200,000 additional persons (Table 1) and a prolonged mean follow-up of 18 days. The additional person-time allowed for less-common outcomes, including Covid-19–related hospitalization and severe disease, to be assessed in many of the subgroups.

Among persons with three or more coexisting conditions, the estimated vaccine effectiveness was 81% (95% confidence interval [CI], 69 to 90) against documented infection and 88% (95% CI, 79 to 95) against symptomatic infection — findings that support the initial indications of potentially reduced vaccine effectiveness in this subgroup. There were also indications of potentially reduced vaccine effectiveness among persons with certain conditions, such as heart disease, chronic kidney disease, and cerebrovascular disease.

The number of control-matched pairs of solid-organ recipients for the period of at least 7 days after receipt of the second dose was too small for the evaluation of vaccine effectiveness. However, when we combined the subgroup of solid-organ recipients with the other category of immunosuppression that was used in our original article to create a combined “immunodeficiency” subgroup, we found that the vaccine effectiveness was 90% (95% CI, 49 to 100) against documented infection and 84% (95% CI, 19 to 100) against symptomatic infection. It should be noted, however, that solid-organ recipients constituted a small minority of this immunodeficiency subgroup.

Noam Barda, M.D., Ph.D.
Noa Dagan, M.D., Ph.D.
Ran D. Balicer, M.D., Ph.D.
Clalit Research Institute, Tel Aviv, Israel

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

This letter was published on April 21, 2021, at NEJM.org.

Estimated Vaccine Effectiveness in Subgroups.*

Subgroup and Period No. of Persons Vaccine Effectiveness (95% CI)
Against Documented Infection Against Symptomatic Infection Against Hospitalization Against Severe Disease
percent
Full study population
14–20 days after first dose 693,814 48 (42 to 52) 56 (51 to 61) 70 (52 to 82) 65 (45 to 80)
21–27 days after first dose 480,438 65 (60 to 69) 71 (66 to 75) 78 (61 to 90) 77 (56 to 91)
7–28 days after second dose 310,696 93 (91 to 94) 96 (94 to 97) 92 (85 to 97) 95 (89 to 99)
Age group
16–39 yr 115,916 94 (92 to 96) 97 (95 to 99) NA NA
40–69 yr 166,592 92 (90 to 94) 95 (93 to 97) 98 (94 to 100) 100 (35 vs. 0)
≥70 yr 28,318 91 (86 to 95) 92 (83 to 97) 81 (57 to 94) 86 (63 to 97)
No. of coexisting conditions
0 179,448 94 (92 to 96) 97 (95 to 99) 98 (91 to 100) 100 (15 vs. 0)
1 or 2 103,792 95 (93 to 96) 95 (93 to 97) 92 (80 to 100) 95 (78 to 100)
≥3 27,478 81 (69 to 90) 88 (79 to 95) 88 (71 to 97) 93 (78 to 100)
Overweight§ 79,440 94 (91 to 97) 96 (93 to 98) 97 (89 to 100) 100 (16 vs. 0)
Obesity§ 40,164 93 (89 to 97) 93 (86 to 97) 97 (90 to 100) 100 (12 vs. 0)
Hypertension 35,056 85 (75 to 92) 90 (84 to 95) 94 (84 to 99) 93 (80 to 100)
Type 2 diabetes mellitus 20,370 86 (76 to 93) 86 (76 to 94) 85 (65 to 100) 91 (71 to 100)
Heart disease 9,144 82 (62 to 93) 80 (60 to 93) 89 (69 to 100) 97 (84 to 100)
Chronic kidney disease 8,212 79 (60 to 92) 80 (57 to 94) 76 (14 to 100) 74 (−40 to 100)
Neurologic disease 3,464 81 (37 to 100) 84 (42 to 100) 69 (−27 to 100) 100 (5 vs. 0)
Cerebrovascular disease 2,762 53 (−42 to 92) 75 (29 to 96) 85 (26 to 100) 91 (43 to 100)
Immunodeficiency 1,674 90 (49 to 100) 84 (19 to 100) 100 (2 vs. 0) 100 (1 vs. 0)

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