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      Humoral response after a fourth dose of SARS-CoV-2 vaccine in immunocompromised patients. Results of a systematic review

      systematic-review

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          Abstract

          Background and objective

          The fourth dose the COVID-19 vaccine was first proposed to immunocompromised patients. The aim of the article is to systematically review the literature and report the humoral response and outcomes after the fourth dose administration in people with impaired immune system.

          Methods

          Published studies on the humoral response, efficacy and safety of the fourth dose of the COVID-19 vaccine were analyzed in various settings of immunocompromised patients. We conducted systematic searches of PubMed, Cochrane Library and WHO COVID-19 Research Database for series published through January 31, 2023, using the search terms “fourth dose” or “second booster” or “4th dose” and “Coronavirus” or “COVID-19” or “SARS-CoV-2.” All articles were selected according to the PRISMA guidelines.

          Results

          A total of 24 articles including 2,838 patients were comprised in the systematic review. All the studies involved immunocompromised patients, including solid organ transplant recipients, patients with autoimmune rheumatic disease, patients with human immunodeficiency virus (HIV) and patients with blood cancers or diseases. Almost all patients received BNT162b2 or mRNA-1273 as fourth dose. All the studies demonstrated the increase of antibody titers after the fourth dose, both in patients who had a serological strong response and in those who had a weak response after the third dose. No serious adverse events after the 4th dose have been reported by 13 studies. COVID-19 infection after the fourth dose ranged from 0 to 21%.

          Conclusion

          The present review highlights the importance of the fourth dose of covid-19 vaccines for immunocompromised patients. Across the included studies, a fourth dose was associated with improved seroconversion and antibody titer levels. In particular, a fourth dose was associated with increasing immunogenicity in organ transplant recipients and patients with hematological cancers, with a very low rate of serious side effects.

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          RoB 2: a revised tool for assessing risk of bias in randomised trials

          Jonathan A C Sterne, Jelena Savović, Matthew J L Page … (2022)
          Article 0 comments Cited 5789 times – based on 0 reviews     Review now
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            Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

            David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2011)
            David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
            Article 0 comments Cited 4993 times – based on 0 reviews     Review now
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              ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions

              Jonathan AC Sterne, Miguel A. Hernán, Barnaby Reeves … (2018)
              Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I (“Risk Of Bias In Non-randomised Studies - of Interventions”), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.
              Article 0 comments Cited 3777 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Public Health
                Journal ID (iso-abbrev): Front Public Health
                Journal ID (publisher-id): Front. Public Health
                Title: Frontiers in Public Health
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-2565
                Publication date (Electronic): 23 March 2023
                Publication date Collection: 2023
                Publication date PMC-release: 23 March 2023
                Volume: 11
                Electronic Location Identifier: 1108546
                Affiliations
                [1] 1Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore , Rome, Italy
                [2] 2Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
                Author notes

                Edited by: Abanoub Riad, Masaryk University, Czechia

                Reviewed by: Ali Tavakoli Pirzaman, Babol University of Medical Sciences, Iran; Mohammed Amir Rais, University of Algiers, Algeria

                *Correspondence: Silvia Martinelli silvia.martinelli04@ 123456icatt.it

                This article was submitted to Infectious Diseases: Epidemiology and Prevention, a section of the journal Frontiers in Public Health

                Article
                DOI: 10.3389/fpubh.2023.1108546
                PMC ID: 10076800
                PubMed ID: 37033069
                SO-VID: c4a85ca6-cfba-4bde-b7bc-9f94519e89b8
                Copyright © Copyright © 2023 Martinelli, Pascucci and Laurenti.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 26 November 2022
                Date accepted : 06 March 2023
                Page count
                Figures: 1, Tables: 6, Equations: 0, References: 51, Pages: 13, Words: 7956
                Categories
                Subject: Public Health
                Subject: Systematic Review

                Keywords: immunocompromised,fourth dose,immune system,second booster,covid-19,sars-cov-2
                Data availability:
                Keywords: immunocompromised, fourth dose, immune system, second booster, covid-19, sars-cov-2

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