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      Association between BNT162b2 vaccination and reported incidence of post-COVID-19 symptoms: cross-sectional study 2020-21, Israel

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          Abstract

          The effectiveness of Coronavirus disease 2019 (COVID-19) vaccines against the long-term COVID-19 symptoms expressed by a substantial proportion of patients is not well understood. We determined whether vaccination with the BNT162b2 mRNA vaccine was associated with incidence of reporting long-term symptoms post-SARS-CoV-2 infection. We invited individuals PCR-tested for SARS-CoV-2 infection at participating hospitals between March 2020 and November 2021 to fill an online questionnaire that included information about demographics, acute COVID-19 episode and symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated and those uninfected, in terms of post-acute self-reported symptoms. Of the 951 infected, 637(67%) were vaccinated. In the study population, the most prevalent symptoms were: fatigue (22%), headache (20%), weakness of limbs (13%), and persistent muscle pain (10%). After adjusting for age, time from beginning of symptoms to responding to the survey, and baseline symptoms, those who received two vaccine doses were less likely than unvaccinated individuals to report any of these symptoms (fatigue, headache, weakness of limbs, persistent muscle pain) by 62%, 50%, 62%, and 66% respectively, (Risk ratios 0.38, 0.50, 0.38, 0.34, p < 0.04 in the listed sequence). Compared to the 2447 included individuals who never reported SARS-CoV-2 infection, double-vaccinated participants were no more likely to report any of the mentioned symptoms. Vaccination with 2+ doses of BNT162b2 was associated with a reduced risk of reporting most of the common post-acute COVID-19 symptoms. Our results suggest that BNT162b2 vaccination may have a protective effect against longer term COVID-19 symptoms.

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          Persistent Symptoms in Patients After Acute COVID-19

          This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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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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              Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

              Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. Methods At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Results Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Conclusions Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.
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                Author and article information

                Contributors
                michael.edelstein@biu.ac.il
                Journal
                NPJ Vaccines
                NPJ Vaccines
                NPJ Vaccines
                Nature Publishing Group UK (London )
                2059-0105
                26 August 2022
                26 August 2022
                2022
                : 7
                : 101
                Affiliations
                [1 ]GRID grid.22098.31, ISNI 0000 0004 1937 0503, Azrieli Faculty of Medicine, , Bar-Ilan University, ; Safed, Israel
                [2 ]Baruch Padeh Medical Centre, Poriya, Israel
                [3 ]Ziv Medical Centre, Safed, Israel
                [4 ]Galilee Medical Centre, Nahariyah, Israel
                Author information
                http://orcid.org/0000-0003-2483-3499
                http://orcid.org/0000-0003-2463-7105
                http://orcid.org/0000-0002-8006-5845
                http://orcid.org/0000-0002-7323-0806
                Article
                526
                10.1038/s41541-022-00526-5
                9411827
                36028498
                fa7263d6-f2cd-4dc0-b132-1e9e0370531c
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 March 2022
                : 9 August 2022
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                © The Author(s) 2022

                fatigue,viral infection
                fatigue, viral infection

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