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      Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

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          Abstract

          Background

          The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.

          Methods

          PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.

          Results

          Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2–66.6; female, 9.0–67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2–85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45–0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43–0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41–0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47–0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3–73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1–42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.

          Conclusions

          COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)
          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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            PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews

            Matthew J Page (2021)
            The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.
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              Bias in meta-analysis detected by a simple, graphical test.

              M. Egger, G Davey Smith, M. Schneider … (1997)
              Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Vaccine
                Journal ID (iso-abbrev): Vaccine
                Title: Vaccine
                Publisher: Elsevier Ltd.
                ISSN (Print): 0264-410X
                ISSN (Electronic): 1873-2518
                Publication date PMC-release: 8 February 2023
                Publication date (Electronic): 8 February 2023
                Affiliations
                [a ]Division of Hospital Medicine, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
                [b ]Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
                [c ]Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
                [d ]Center for Cardiovascular Research, The Abigail Wexner Research Institute and The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA
                [e ]Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan
                [f ]Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA
                Author notes
                [* ]Corresponding author at: Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, New York, NY 10467-2401, USA.
                Article
                Publisher Item ID: S0264-410X(23)00134-2
                DOI: 10.1016/j.vaccine.2023.02.008
                PMC ID: 9905096
                PubMed ID: 36774332
                SO-VID: ad78661a-8ed0-42b1-88ab-2d40b61fd0cd
                Copyright © © 2023 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 19 October 2022
                Date revision received : 4 January 2023
                Date accepted : 3 February 2023
                Categories
                Subject: Review

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: covid-19,vaccine,sars-cov-2,long covid,post-acute sequelae of covid-19,ci, confidence interval,covid-19, coronavirus disease 2019,ct, computed tomography,grade, grading recommendations assessment, development, and evaluation,icu, intensive care unit,or, odds ratio,prisma, preferred reporting items for systematic reviews and meta-analyses,rt-pcr, reverse transcriptase-polymerase chain reaction,sars-cov-2, severe acute respiratory syndrome coronavirus 2
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: covid-19, vaccine, sars-cov-2, long covid, post-acute sequelae of covid-19, ci, confidence interval, covid-19, coronavirus disease 2019, ct, computed tomography, grade, grading recommendations assessment, development, and evaluation, icu, intensive care unit, or, odds ratio, prisma, preferred reporting items for systematic reviews and meta-analyses, rt-pcr, reverse transcriptase-polymerase chain reaction, sars-cov-2, severe acute respiratory syndrome coronavirus 2

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