{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:20:53Z","timestamp":1787509253014,"version":"build-2736575974"},"reference-count":78,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-66\/2024-03\/200019"],"award-info":[{"award-number":["451-03-66\/2024-03\/200019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mem. Inst. Oswaldo Cruz"],"abstract":"<jats:p>BACKGROUND  Through coevolution, helminths have developed immunomodulatory mechanisms that regulate exaggerated host immune responses and may influence immune responses to coinfections or vaccines. The coronavirus disease 19 (COVID-19) pandemic has raised concerns about how such infections might affect vaccine-triggered immune responses.  OBJECTIVES  The aim of the study was to investigate how ongoing Trichinella spiralis infection affects the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in individuals already vaccinated or virus-primed, during Trichinella outbreak in Serbia.  METHODS  Among 21 individuals who tested positive for anti-Trichinella antibodies, 15 were included in the study, which allowed for the first time to examine the impact of Trichinella infection on the humoral and cellular immune response to the SARS-CoV-2 using flow cytometry.  FINDINGS  The results showed that Trichinella infection did not impair antibody production or cellular responses to SARS-CoV-2. Specifically, anti-SARS-CoV-2 antibodies and memory B cells remain unaffected, and T cells (CD4+ and CD8+) responded to SARS-CoV-2 antigens by generating pro-inflammatory cytokines.  MAIN CONCLUSIONS Trichinella spiralis infection does not disrupt the host\u2019s humoral or cellular immune response to SARS-CoV-2, suggesting that the use of Trichinella antigens for the treatment of chronic inflammatory disorders, which is promising, will not affect the host\u2019s ability to respond to future viral challenges.<\/jats:p>","DOI":"10.1590\/0074-02760250044","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:04:15Z","timestamp":1760972655000},"source":"Crossref","is-referenced-by-count":3,"title":["Patients with Trichinella spiralis infection display unmodified antigen-specific immune response to SARS-CoV-2"],"prefix":"10.1590","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-4213","authenticated-orcid":false,"given":"Ivana","family":"Mitic","sequence":"first","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Glamoclija","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasa","family":"Radulovic","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia; University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Sabljic","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergej","family":"Tomic","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Gruden-Movsesijan","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Sofronic-Milosavljevic","sequence":"additional","affiliation":[{"name":"University of Belgrade,  Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"key":"ref1","article-title":"T cell immune memory after covid-19 and vaccination","author":"Wang L","year":"2023","journal-title":"BMJ Med"},{"key":"ref2","article-title":"mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern","author":"Goel RR","year":"2021","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.01.050","article-title":"Maturation and persistence of the anti-SARS-CoV-2 memory B cell response","author":"Sokal A","year":"2021","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0249499","article-title":"Human IgG and IgA responses to COVID-19 mRNA vaccines","author":"Wisnewski AV","year":"2021","journal-title":"PLoS One"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1038\/s41423-021-00708-6","article-title":"Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection","author":"Wang H","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"ref6","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa2026116","article-title":"Humoral immune response to SARS-CoV-2 in Iceland","author":"Gudbjartsson DF","year":"2020","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","DOI":"10.1038\/s41577-020-0321-6","article-title":"The potential danger of suboptimal antibody responses in COVID-19","author":"Iwasaki A","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"ref8","article-title":"Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection","author":"Dan JM","year":"2021","journal-title":"Science"},{"key":"ref9","article-title":"Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity","author":"Moderbacher CR","year":"2020","journal-title":"Cell"},{"key":"ref10","article-title":"Malaria and COVID-19: unmasking their ties","author":"Hussein MIH","year":"2020","journal-title":"Malaria Journal"},{"key":"ref11","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1233082","article-title":"Negative association between ascaris lumbricoides seropositivity and Covid-19 severity: insights from a study in Benin","author":"Adjobimey T","year":"2023","journal-title":"Front Immunol"},{"key":"ref12","article-title":"COVID-19 unfolding filariasis: the first case of SARS-CoV-2 and Wuchereria bancrofti coinfection","author":"Mohamed MFH","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"ref13","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.05040-11","article-title":"Helminth infections and host immune regulation","author":"McSorley HJ","year":"2012","journal-title":"Clin Microbiol Rev"},{"key":"ref14","article-title":"Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities","author":"Ryan SM","year":"2020","journal-title":"PLoS Pathog"},{"key":"ref15","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2018.10.016","article-title":"Modulation of host immunity by helminths: the expanding repertoire of parasite effector molecules","author":"Maizels RM","year":"2018","journal-title":"Immunity"},{"key":"ref16","doi-asserted-by":"crossref","DOI":"10.1016\/j.pt.2017.05.007","article-title":"Can parasitic worms cure the modern world\u2019s ills?","author":"Harnett MM","year":"2017","journal-title":"Trends Parasitol"},{"key":"ref17","doi-asserted-by":"crossref","DOI":"10.1007\/s12026-015-8626-4","article-title":"Immunomodulatory effects of Trichinella spiralis-derived excretory-secretory antigens","author":"Radovic I","year":"2015","journal-title":"Immunol Res"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00563-12","article-title":"Hookworm excretory\/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis","author":"Ferreira I","year":"2013","journal-title":"Infect Immun"},{"key":"ref19","doi-asserted-by":"crossref","DOI":"10.1007\/s00430-012-0286-6","article-title":"Application of dendritic cells stimulated with Trichinella spiralis excretory-secretory antigens alleviates experimental autoimmune encephalomyelitis","author":"Sofronic-Milosavljevic LJ","year":"2013","journal-title":"Med Microbiol Immunol"},{"key":"ref20","doi-asserted-by":"crossref","DOI":"10.1002\/eji.201142161","article-title":"Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus","author":"McSorley HJ","year":"2012","journal-title":"Eur J Immunol"},{"key":"ref21","article-title":"Hook worm products ameliorate dextran sodium sulfate-induced colitis in BALB\/c mice","author":"Can\u00e7ado GG","year":"2011","journal-title":"Inflamm Bowel Dis"},{"key":"ref22","doi-asserted-by":"crossref","DOI":"10.1002\/ibd.20787","article-title":"Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice","author":"Ruyssers NE","year":"2009","journal-title":"Inflamm Bowel Dis"},{"key":"ref23","doi-asserted-by":"crossref","DOI":"10.1016\/S0169-4758(98)01287-3","article-title":"How does Trichinella spiralis make itself at home?","author":"Despommier DD","year":"1998","journal-title":"Parasitol Today"},{"key":"ref24","article-title":"Trichinella-induced immunomodulation: another tale of helminth success","author":"Bruschi F","year":"2022","journal-title":"Food Waterborne Parasitol"},{"key":"ref25","article-title":"Trichinella spiralis: nurse cell formation with emphasis on analogy to muscle cell repair","author":"Wu Z","year":"2008","journal-title":"Parasit Vectors"},{"key":"ref26","article-title":"Immunity to Trichinella. In: Bruschi F, editor. Trichinella and trichinellosis","author":"Grencis RK","year":"2021","journal-title":"Academic Press"},{"key":"ref27","doi-asserted-by":"crossref","DOI":"10.1111\/pim.12665","article-title":"Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties","author":"Kosanovic M","year":"2019","journal-title":"Parasite Immunol"},{"key":"ref28","doi-asserted-by":"crossref","DOI":"10.1007\/s00436-008-1248-1","article-title":"Functional genes and proteins of Trichinella spp","author":"Nagano I","year":"2009","journal-title":"Parasitol Res"},{"key":"ref29","article-title":"Induction of the IL-10-producing regulatory B cell phenotype following Trichinella spiralis infection","author":"Xie J","year":"2021","journal-title":"Mol Immunol"},{"key":"ref30","article-title":"Trichinella spiralis thioredoxin peroxidase 2 regulates protective Th2 immune response in mice by directly inducing alternatively activated macrophages","author":"Jin QW","year":"2020","journal-title":"Front Immunol"},{"key":"ref31","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2016.07.007","article-title":"Regulation of the host immune system by helminth parasites","author":"Maizels RM","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"ref32","article-title":"Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases","author":"Finlay CM","year":"2014","journal-title":"Immunol Rev"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1111\/all.13944","article-title":"Regulation of immunity and allergy by helminth parasites","author":"Maizels RM","year":"2020","journal-title":"Allergy"},{"key":"ref34","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.02349","article-title":"Immunomodulation by helminths: intracellular pathways and extracellular vesicles","author":"Zakeri A","year":"2018","journal-title":"Front Immunol"},{"key":"ref35","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2019.10.051","article-title":"Helminth infections suppress the efficacy of vaccination against seasonal influenza","author":"Hartmann W","year":"2019","journal-title":"Cell Rep"},{"key":"ref36","doi-asserted-by":"crossref","DOI":"10.1007\/s00430-014-0344-3","article-title":"Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens","author":"Apiwattanakul N","year":"2014","journal-title":"Med Microbiol Immunol"},{"key":"ref37","doi-asserted-by":"crossref","DOI":"10.1017\/S0950268823000109","article-title":"Trichinella infection in Serbia from 2011 to 2020: a success story in the field of One Health","author":"Vasilev S","year":"2023","journal-title":"Epidemiol Infect"},{"key":"ref38","doi-asserted-by":"crossref","DOI":"10.1016\/j.vetpar.2005.05.047","article-title":"Re-emergence of trichinelosis in Southeastern Europe due to political and economic changes","author":"Cuperlovic K","year":"2005","journal-title":"Vet Parasitol"},{"key":"ref39","article-title":"Epidemiology of swine trichinelosis in Yugoslavia","author":"Cuperlovic K","year":"1991","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"ref40","series-title":"FAO\/WHO\/OIE Guidelines for the surveillance, management, prevention and control of trichinellosis","author":"Dupouy-Camet J","year":"2007"},{"key":"ref41","article-title":"Commission implementing decision (EU) 2018\/945 on 22 June 2018 on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions","year":"2018","journal-title":"OJ L170"},{"key":"ref42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007157","article-title":"Effect of Schistosoma mansoni infection and its treatment on antibody responses to measles catch-up immunisation in pre-school children: a randomised trial","author":"Tweyongyere R","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"ref43","article-title":"Schistosomiasis burden and its association with lower measles vaccine responses in school children from rural Cameroon","author":"Nono JK","year":"2018","journal-title":"Front Immunol"},{"key":"ref44","doi-asserted-by":"crossref","DOI":"10.1093\/infdis\/jiw066","article-title":"Maternal helminth infection is associated with higher infant immunoglobulin A titers to antigen in orally administered vaccines","author":"Clark CE","year":"2016","journal-title":"J Infect Dis"},{"key":"ref45","article-title":"Schistosoma mansoni infection can jeopardize the duration of protective levels of antibody responses to immunizations against hepatitis B and tetanus toxoid","author":"Riner DK","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ref46","doi-asserted-by":"crossref","DOI":"10.1016\/j.vaccine.2014.07.107","article-title":"Chronic helminth infections impair pneumococcal vaccine responses","author":"Apiwattanakul N","year":"2014","journal-title":"Vaccine"},{"key":"ref47","article-title":"Impact of malaria and helminth infections on immunogenicity of the human papillomavirus-16\/18 AS04-adjuvanted vaccine in Tanzania","author":"Brown J","year":"2014","journal-title":"Vaccine"},{"key":"ref48","article-title":"Reduced antibody responses against Plasmodium falciparum vaccine candidate antigens in the presence of Trichuris trichiura","author":"Esen M","year":"2012","journal-title":"Vaccine"},{"key":"ref49","article-title":"Immunologic responses to Vibrio cholerae in patients co-infected with intestinal parasites in Bangladesh","author":"Harris JB","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"ref50","article-title":"How protective are antibodies to SARS-CoV-2, the main weapon of the B-Cell response?","author":"Pons S","year":"2023","journal-title":"Stem Cell Rev and Rep"},{"key":"ref51","doi-asserted-by":"crossref","DOI":"10.1093\/infdis\/jiad518","article-title":"Immunosuppressive ability of Trichinella spiralis adults can ameliorate type 2 inflammation in a murine allergy model","author":"Shi W","year":"2024","journal-title":"J Infect Dis"},{"key":"ref52","article-title":"Trichinella spiralis: inflammation modulator","author":"Ding J","year":"2020","journal-title":"J Helminthol"},{"key":"ref53","article-title":"The impact of parasite infections on the course of multiple sclerosis","author":"Correale J","year":"2011","journal-title":"J Neuroimmunol"},{"key":"ref54","article-title":"Association between parasite infection and immune responses in multiple sclerosis","author":"Correale J","year":"2007","journal-title":"Ann Neurol"},{"key":"ref55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0009402","article-title":"COVID-19 and helminth infection: Beyond the Th1\/Th2 paradigm","author":"Paniz-Mondolfi AE","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"ref56","article-title":"S. mansoni bolsters anti-viral immunity in the murine respiratory tract","author":"Scheer S","year":"2014","journal-title":"PLoS One"},{"key":"ref57","article-title":"Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection","author":"Rolot M","year":"2018","journal-title":"Nat Commun"},{"key":"ref58","article-title":"The helminth-derived immunomodulator AvCystatin reduces virus enhanced inflammation by induction of regulatory IL-10+ T Cells","author":"Schuijs MJ","year":"2016","journal-title":"PLoS One"},{"key":"ref59","article-title":"Amelioration of influenza-induced pathology in mice by coinfection with Trichinella spiralis","author":"Furze RC","year":"2006","journal-title":"Infect Immun"},{"key":"ref60","article-title":"Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation","author":"Osborne LC","year":"2014","journal-title":"Science"},{"key":"ref61","article-title":"Functional SARS-CoV-2-specific immune memory persists after mild COVID-19","author":"Rodda LB","year":"2021","journal-title":"Cell"},{"key":"ref62","article-title":"Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration","author":"Newell KL","year":"2021","journal-title":"PLoS One"},{"key":"ref63","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02631","article-title":"Heterologous immunity: role in natural and vaccine-induced resistance to infections","author":"Agrawal B","year":"2019","journal-title":"Front Immunol"},{"key":"ref64","article-title":"Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells","author":"Mateus J","year":"2021","journal-title":"Science"},{"key":"ref65","article-title":"Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2.","author":"Low JS","year":"2021","journal-title":"Science"},{"key":"ref66","article-title":"Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination","author":"Loyal L","year":"2021","journal-title":"Science"},{"key":"ref67","article-title":"Preliminary Trichinella spiralis infection ameliorates subsequent RSV infection-induced inflammatory response","author":"Chu KB","year":"2020","journal-title":"Cells"},{"key":"ref68","article-title":"The resistance against Trichinella spiralis infection induced by primary infection with respiratory syncytial virus","author":"Chu KB","year":"2019","journal-title":"Parasitology"},{"key":"ref69","article-title":"Robust T Cell immunity in convalescent individuals with asymptomatic or mild COVID-19","author":"Sekine T","year":"2020","journal-title":"Cell"},{"key":"ref70","article-title":"Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses","author":"Zhou R","year":"2020","journal-title":"Immunity"},{"key":"ref71","doi-asserted-by":"crossref","DOI":"10.1038\/s41590-020-0782-6","article-title":"Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19","author":"Peng Y","year":"2020","journal-title":"Nat Immunol"},{"key":"ref72","doi-asserted-by":"crossref","DOI":"10.1051\/parasite\/2019074","article-title":"Regulation of host immune cells and cytokine production induced by Trichinella spiralis infection","author":"Song Y","year":"2019","journal-title":"Parasite"},{"key":"ref73","article-title":"Trichinella spiralis antigens prime mixed Th1\/Th2 response but do not induce de novo generation of Foxp3+ T cells in vitro","author":"Ilic N","year":"2011","journal-title":"Parasite Immunol"},{"key":"ref74","article-title":"Trichinella spiralis excretory-secretory products induce tolerogenic properties in human dendritic cells via toll-like receptors 2 and 4","author":"Ilic N","year":"2018","journal-title":"Front Immunol"},{"key":"ref75","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.70.1.233-239.2002","article-title":"Increased CD8+-T cell expression and a Type 2 cytokine pattern during the musculature phase of Trichinella infection in humans","author":"Gomez-Morales MA","year":"2002","journal-title":"Infect Immun"},{"key":"ref76","article-title":"Tissue-specific immunity in helminth infections","author":"Vacca F","year":"2022","journal-title":"Mucosal Immunol"},{"key":"ref77","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T Cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals","author":"Grifoni A","year":"2020","journal-title":"Cell"},{"key":"ref78","article-title":"Long lasting immunity in trichinellosis - insight from a small study group.","author":"Ilic N","year":"2022","journal-title":"J Helminthol"}],"container-title":["Mem\u00f3rias do Instituto Oswaldo Cruz"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0074-02762025000101150&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:04:24Z","timestamp":1760972664000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0074-02762025000101150&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":78,"alternative-id":["S0074-02762025000101150"],"URL":"https:\/\/doi.org\/10.1590\/0074-02760250044","relation":{},"ISSN":["1678-8060","0074-0276"],"issn-type":[{"value":"1678-8060","type":"electronic"},{"value":"0074-0276","type":"print"}],"subject":[],"published":{"date-parts":[[2025]]},"article-number":"e250044"}}