Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis
Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. From January...
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| Published in | Circulation (New York, N.Y.) Vol. 147; no. 11; pp. 867 - 876 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Lippincott Williams & Wilkins
14.03.2023
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.
From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects.
Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired
test;
<0.0001).
Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause. |
|---|---|
| AbstractList | Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.
From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects.
Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired
test;
<0.0001).
Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause. Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.BACKGROUNDCases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail.From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects.METHODSFrom January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects.Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001).RESULTSExtensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001).Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.CONCLUSIONSImmunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause. |
| Author | Cheng, Chi-An Dionne, Audrey Balaguru, Duraisamy Kane, Abigail Yonker, Lael M. Loiselle, Maggie Edlow, Andrea G. Lahoud-Rahme, Manuella Walt, David R. Burns, Madeleine D. Burgess, Eleanor Davis, Jameson P. Julg, Boris Swank, Zoe Chou, Janet Alter, Galit Boribong, Brittany P. Novak, Tanya Senussi, Yasmeen Randolph, Adrienne G. Bartsch, Yannic C. Fasano, Alessio Arditi, Moshe |
| AuthorAffiliation | Department of Pediatrics, Division of Infectious Diseases and Immunology, Infectious and Immunologic Diseases Research Center, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA (M.A.) Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) Ragon Institute of MGH, MIT and Harvard, Cambridge, MA (Y.C.B., E.B., B.J., G.A.) |
| AuthorAffiliation_xml | – name: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA (Y.C.B., E.B., B.J., G.A.) – name: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – name: Department of Pediatrics, Division of Infectious Diseases and Immunology, Infectious and Immunologic Diseases Research Center, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA (M.A.) |
| Author_xml | – sequence: 1 givenname: Lael M. surname: Yonker fullname: Yonker, Lael M. organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 2 givenname: Zoe surname: Swank fullname: Swank, Zoe organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 3 givenname: Yannic C. surname: Bartsch fullname: Bartsch, Yannic C. organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 4 givenname: Madeleine D. surname: Burns fullname: Burns, Madeleine D. organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 5 givenname: Abigail surname: Kane fullname: Kane, Abigail organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 6 givenname: Brittany P. surname: Boribong fullname: Boribong, Brittany P. organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 7 givenname: Jameson P. surname: Davis fullname: Davis, Jameson P. organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 8 givenname: Maggie surname: Loiselle fullname: Loiselle, Maggie organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 9 givenname: Tanya surname: Novak fullname: Novak, Tanya organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 10 givenname: Yasmeen surname: Senussi fullname: Senussi, Yasmeen organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 11 givenname: Chi-An surname: Cheng fullname: Cheng, Chi-An organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 12 givenname: Eleanor surname: Burgess fullname: Burgess, Eleanor organization: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA (Y.C.B., E.B., B.J., G.A.) – sequence: 13 givenname: Andrea G. surname: Edlow fullname: Edlow, Andrea G. organization: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology (A.G.E.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 14 givenname: Janet surname: Chou fullname: Chou, Janet organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 15 givenname: Audrey surname: Dionne fullname: Dionne, Audrey organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 16 givenname: Duraisamy surname: Balaguru fullname: Balaguru, Duraisamy organization: Department of Pediatrics (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., D.B., M.L.-R., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 17 givenname: Manuella surname: Lahoud-Rahme fullname: Lahoud-Rahme, Manuella organization: Department of Pediatrics (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., D.B., M.L.-R., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 18 givenname: Moshe surname: Arditi fullname: Arditi, Moshe organization: Department of Pediatrics, Division of Infectious Diseases and Immunology, Infectious and Immunologic Diseases Research Center, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA (M.A.) – sequence: 19 givenname: Boris surname: Julg fullname: Julg, Boris organization: Department of Medicine (B.J.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 20 givenname: Adrienne G. surname: Randolph fullname: Randolph, Adrienne G. organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 21 givenname: Galit surname: Alter fullname: Alter, Galit organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) – sequence: 22 givenname: Alessio surname: Fasano fullname: Fasano, Alessio organization: Mucosal Immunology and Biology Research Center (L.M.Y., M.D.B., A.K., B.P.B., J.P.D., M.L., A.F.), Division of Infectious Disease, Massachusetts General Hospital, Boston – sequence: 23 givenname: David R. surname: Walt fullname: Walt, David R. organization: Harvard Medical School, Boston, MA (L.M.Y., Z.S., Y.C.B., B.P.B., T.N., Y.S., C.-A.C., J.C., A.D., D.B., M.L.-R., B.J., A.G.R., G.A., A.F., D.R.W.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36597886$$D View this record in MEDLINE/PubMed |
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| Copyright | Lippincott Williams & Wilkins 2023 American Heart Association, Inc. 2023 |
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| Snippet | Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA... Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–targeted mRNA... |
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| SubjectTerms | Adolescent Antibodies, Viral Autoantibodies Child COVID-19 - prevention & control COVID-19 Vaccines - adverse effects Cytokines Humans Myocarditis - etiology Original s SARS-CoV-2 Spike Glycoprotein, Coronavirus Young Adult |
| Title | Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis |
| URI | https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00003017-202303140-00004 https://www.ncbi.nlm.nih.gov/pubmed/36597886 https://www.proquest.com/docview/2760821287 https://pubmed.ncbi.nlm.nih.gov/PMC10010667 |
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