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      Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings

      research-article
      , Ph.D. , , M.D., , M.D., , Sc.D., , Ph.D., , Ph.D., , M.D., M.P.H., , Ph.D., , Ph.D., M.P.H., , M.P.H., , M.D., Ph.D., , M.P.A., Ph.D., , M.P.H., , M.H.S., , M.D., , M.D., M.P.H., , B.S., , Ph.D., M.P.H., , M.P.H., , M.P.P., , Ph.D., , Ph.D., , Ph.D., , M.A., , M.P.H., , Dr.P.H., , Dr.P.H., , M.B., B.S., M.P.H., , Ph.D., , M.P.H., , M.P.H., , Ph.D., , M.P.H., , M.P.H., , Ph.D., , M.P.H., , M.D., , R.N., , D.Phil., , M.D., M.P.H., , M.D., M.P.H., , M.B., B.S., , M.D., M.P.H., , M.D., Ph.D.
      The New England Journal of Medicine
      Massachusetts Medical Society
      Keyword part (code): 18Keyword part (keyword): Infectious DiseaseKeyword part (code): 18_2Keyword part (keyword): VaccinesKeyword part (code): 18_6Keyword part (keyword): Viral InfectionsKeyword part (code): 18_12Keyword part (keyword): Coronavirus , 18, Infectious Disease, Keyword part (code): 18_2Keyword part (keyword): VaccinesKeyword part (code): 18_6Keyword part (keyword): Viral InfectionsKeyword part (code): 18_12Keyword part (keyword): Coronavirus , 18_2, Vaccines, 18_6, Viral Infections, 18_12, Coronavirus

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          Abstract

          Background

          There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic.

          Methods

          We conducted a study involving adults (≥50 years of age) with Covid-19–like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation.

          Results

          The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19–associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit.

          Conclusions

          Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.)

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

              Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.
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                Author and article information

                Journal
                N Engl J Med
                N Engl J Med
                nejm
                The New England Journal of Medicine
                Massachusetts Medical Society
                0028-4793
                1533-4406
                08 September 2021
                : NEJMoa2110362
                Affiliations
                From the Centers for Disease Control and Prevention COVID-19 Response Team, Atlanta (M.G.T., C.H.B., S. Reynolds, J.F., P.P., E.P.G., R.M.P., L.B., A.S., N.O., S.J.S., J.R.V., A.F., E.A.-B.); the Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare, Salt Lake City (E.S., K.D., N.G., J.A.); the Center for Biomedical Informatics, Regenstrief Institute (S.G., B.E.D., W.F.F., N.R.V.), Indiana University School of Medicine (S.G.), and Indiana University Richard M. Fairbanks School of Public Health (B.E.D., W.F.F., N.R.V.) — all in Indianapolis; Westat, Rockville, MD (S.W.B., R.J.B., M.E.L., E.A.R., M.D., Y.Z., P.S.); the Kaiser Permanente Northwest Center for Health Research, Portland, OR (A.L.N., S.A.I.); the Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora (T.C.O., S. Rao, M.B.); HealthPartners Institute, Minneapolis (M.B.D., E.K.); the Department of Biomedical Informatics, Columbia University Irving Medical Center (K.N., J.H.), and New York–Presbyterian Hospital (K.N.) — both in New York; the Vaccine Study Center, Division of Research, Kaiser Permanente Northern California, Oakland (N.L., K.G., B.F., O.Z., N.P.K.); and Baylor Scott and White Health, Texas A&M University College of Medicine, Temple, TX (M.G.).
                Author notes
                Address reprint requests to Dr. Thompson at the Influenza Division, Mailstop A32, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, GA 30333, or at isq8@ 123456cdc.gov .
                Author information
                http://orcid.org/0000-0001-6566-7138
                Article
                NJ202109083851501
                10.1056/NEJMoa2110362
                8451184
                34496194
                2b0f48e7-a1ca-4cd5-914f-2869bd843ce8
                Copyright © 2021 Massachusetts Medical Society. All rights reserved.

                This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.

                History
                Funding
                Funded by: National Center for Immunization and Respiratory Diseases, FundRef http://dx.doi.org/10.13039/100005224;
                Award ID: 75D30120C07765
                Award ID: 75D30120C07986
                Categories
                Original Article
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                2021-09-08T17:00:00-04:00
                2021
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