Loading…
Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals
Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. A...
Saved in:
Published in: | Vaccines (Basel) 2023-12, Vol.11 (12), p.1835 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63 |
---|---|
cites | cdi_FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63 |
container_end_page | |
container_issue | 12 |
container_start_page | 1835 |
container_title | Vaccines (Basel) |
container_volume | 11 |
creator | Erice, Alejo Prieto, Lola Caballero, Cristina |
description | Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (
< 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting. |
doi_str_mv | 10.3390/vaccines11121835 |
format | article |
fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_e72a39fe6a3b4ee6818d592d94207f92</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A779344901</galeid><doaj_id>oai_doaj_org_article_e72a39fe6a3b4ee6818d592d94207f92</doaj_id><sourcerecordid>A779344901</sourcerecordid><originalsourceid>FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63</originalsourceid><addsrcrecordid>eNptU8FO3DAUTKtWBQH3nipLvXAJje0kjnupwraUlRBUsEXtKXLil8U0sbd2smj_vm_ZLQXU5GDrZWaeM_McRW9pcsS5TD4sVdMYC4FSymjBs5fRLktEHnPJf7x6tN-JDkK4TfCRlBe5eBPt8IKmCeNy98X-mbPzeAa-J6VV3SpAIK4lV-XlVTxx1zEjp2PvvOqIsprMyAS6jlxCWDi7hq6Lxx7Ur-HGu3F-85g4tS00g0EgUe0AnszuHPnsth2Oz2c0ZzUjJ67r3B1oUq9If3lexpQJvhE2S9WBHchFbxrvbFxqtRgQ-cC93lrwkZTkm3dhsW64BHI1jHpF3BKbMvITlA_EWHKOEtO-H61rXL_wrjcBxaZWm6XRo-rCfvS6xQUOtute9P3ky2xyGp9dfJ1OyrO4ybJiiDmthUxomosaRKNBiFrmdVYDZXioGlJZFACNlFRqTjWkQnElIM0lTVOqc74XTTe62qnbauFNr_yqcspU9wXn55Xyg2k6qEAwxWULueJ1CpAXtNCZZFqmmG8rGWp92mgtxroH3aBfmNYT0adfrLmp5m5Z0USkBefr0xxuFbz7PUIYKjSmwZyVBTeGiskky1iOE4PQ98-gt270ODf3qFQyNIX9Q80xvsrY1mHjZi1alUJInqboHqKO_oPCVwPG7Sy0ButPCMmGgLMQgof24SdpUq1vRPX8RiDl3WNzHgh_55__AZxuBck</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2904921462</pqid></control><display><type>article</type><title>Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database</source><creator>Erice, Alejo ; Prieto, Lola ; Caballero, Cristina</creator><creatorcontrib>Erice, Alejo ; Prieto, Lola ; Caballero, Cristina</creatorcontrib><description>Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (
< 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting.</description><identifier>ISSN: 2076-393X</identifier><identifier>EISSN: 2076-393X</identifier><identifier>DOI: 10.3390/vaccines11121835</identifier><identifier>PMID: 38140239</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Asymptomatic ; bivalent Omicron-adapted vaccine ; BNT162b2 ; COVID-19 ; Evaluation ; Females ; Gender ; Health aspects ; Immune response ; Immune system ; Immunoassay ; Immunomodulation ; Infections ; Lymphocytes ; Lymphocytes T ; mRNA ; mRNA vaccines ; mRNA-1273 ; SARS-CoV-2 ; SARS-CoV-2 antibody humoral immune response ; SARS-CoV-2 vaccine ; Severe acute respiratory syndrome coronavirus 2 ; T cells ; Vaccines ; γ-Interferon</subject><ispartof>Vaccines (Basel), 2023-12, Vol.11 (12), p.1835</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63</citedby><cites>FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63</cites><orcidid>0000-0002-5836-2632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2904921462/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2904921462?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38140239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Erice, Alejo</creatorcontrib><creatorcontrib>Prieto, Lola</creatorcontrib><creatorcontrib>Caballero, Cristina</creatorcontrib><title>Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals</title><title>Vaccines (Basel)</title><addtitle>Vaccines (Basel)</addtitle><description>Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (
< 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting.</description><subject>Antibodies</subject><subject>Asymptomatic</subject><subject>bivalent Omicron-adapted vaccine</subject><subject>BNT162b2</subject><subject>COVID-19</subject><subject>Evaluation</subject><subject>Females</subject><subject>Gender</subject><subject>Health aspects</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunoassay</subject><subject>Immunomodulation</subject><subject>Infections</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>mRNA</subject><subject>mRNA vaccines</subject><subject>mRNA-1273</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 antibody humoral immune response</subject><subject>SARS-CoV-2 vaccine</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>T cells</subject><subject>Vaccines</subject><subject>γ-Interferon</subject><issn>2076-393X</issn><issn>2076-393X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptU8FO3DAUTKtWBQH3nipLvXAJje0kjnupwraUlRBUsEXtKXLil8U0sbd2smj_vm_ZLQXU5GDrZWaeM_McRW9pcsS5TD4sVdMYC4FSymjBs5fRLktEHnPJf7x6tN-JDkK4TfCRlBe5eBPt8IKmCeNy98X-mbPzeAa-J6VV3SpAIK4lV-XlVTxx1zEjp2PvvOqIsprMyAS6jlxCWDi7hq6Lxx7Ur-HGu3F-85g4tS00g0EgUe0AnszuHPnsth2Oz2c0ZzUjJ67r3B1oUq9If3lexpQJvhE2S9WBHchFbxrvbFxqtRgQ-cC93lrwkZTkm3dhsW64BHI1jHpF3BKbMvITlA_EWHKOEtO-H61rXL_wrjcBxaZWm6XRo-rCfvS6xQUOtute9P3ky2xyGp9dfJ1OyrO4ybJiiDmthUxomosaRKNBiFrmdVYDZXioGlJZFACNlFRqTjWkQnElIM0lTVOqc74XTTe62qnbauFNr_yqcspU9wXn55Xyg2k6qEAwxWULueJ1CpAXtNCZZFqmmG8rGWp92mgtxroH3aBfmNYT0adfrLmp5m5Z0USkBefr0xxuFbz7PUIYKjSmwZyVBTeGiskky1iOE4PQ98-gt270ODf3qFQyNIX9Q80xvsrY1mHjZi1alUJInqboHqKO_oPCVwPG7Sy0ButPCMmGgLMQgof24SdpUq1vRPX8RiDl3WNzHgh_55__AZxuBck</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Erice, Alejo</creator><creator>Prieto, Lola</creator><creator>Caballero, Cristina</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T7</scope><scope>7XB</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5836-2632</orcidid></search><sort><creationdate>20231201</creationdate><title>Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals</title><author>Erice, Alejo ; Prieto, Lola ; Caballero, Cristina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antibodies</topic><topic>Asymptomatic</topic><topic>bivalent Omicron-adapted vaccine</topic><topic>BNT162b2</topic><topic>COVID-19</topic><topic>Evaluation</topic><topic>Females</topic><topic>Gender</topic><topic>Health aspects</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunoassay</topic><topic>Immunomodulation</topic><topic>Infections</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>mRNA</topic><topic>mRNA vaccines</topic><topic>mRNA-1273</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 antibody humoral immune response</topic><topic>SARS-CoV-2 vaccine</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>T cells</topic><topic>Vaccines</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erice, Alejo</creatorcontrib><creatorcontrib>Prieto, Lola</creatorcontrib><creatorcontrib>Caballero, Cristina</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest research library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Vaccines (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erice, Alejo</au><au>Prieto, Lola</au><au>Caballero, Cristina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals</atitle><jtitle>Vaccines (Basel)</jtitle><addtitle>Vaccines (Basel)</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>11</volume><issue>12</issue><spage>1835</spage><pages>1835-</pages><issn>2076-393X</issn><eissn>2076-393X</eissn><abstract>Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (
< 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38140239</pmid><doi>10.3390/vaccines11121835</doi><orcidid>https://orcid.org/0000-0002-5836-2632</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2076-393X |
ispartof | Vaccines (Basel), 2023-12, Vol.11 (12), p.1835 |
issn | 2076-393X 2076-393X |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_e72a39fe6a3b4ee6818d592d94207f92 |
source | Open Access: PubMed Central; Publicly Available Content Database |
subjects | Antibodies Asymptomatic bivalent Omicron-adapted vaccine BNT162b2 COVID-19 Evaluation Females Gender Health aspects Immune response Immune system Immunoassay Immunomodulation Infections Lymphocytes Lymphocytes T mRNA mRNA vaccines mRNA-1273 SARS-CoV-2 SARS-CoV-2 antibody humoral immune response SARS-CoV-2 vaccine Severe acute respiratory syndrome coronavirus 2 T cells Vaccines γ-Interferon |
title | Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T15%3A36%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long-Term%20Analyses%20of%20SARS-CoV-2%20Humoral%20and%20T%20Cell%20Responses%20and%20Breakthrough%20SARS-CoV-2%20Infections%20after%20Two%20Doses%20of%20BNT162b2%20Followed%20by%20mRNA-1273%20and%20Bivalent%20Omicron-Adapted%20BNT162b2%20Vaccines:%20A%20Prospective%20Study%20over%202%20Years%20in%20Non-Immunocompromised%20Individuals&rft.jtitle=Vaccines%20(Basel)&rft.au=Erice,%20Alejo&rft.date=2023-12-01&rft.volume=11&rft.issue=12&rft.spage=1835&rft.pages=1835-&rft.issn=2076-393X&rft.eissn=2076-393X&rft_id=info:doi/10.3390/vaccines11121835&rft_dat=%3Cgale_doaj_%3EA779344901%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c558t-31b7901467be7cde77b96b5be122b2be4988eec9919d31de47a3a7e4691441d63%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2904921462&rft_id=info:pmid/38140239&rft_galeid=A779344901&rfr_iscdi=true |