Serological response to vaccination in post-acute sequelae of COVID
Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-pr...
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| Published in | BMC infectious diseases Vol. 23; no. 1; p. 97 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BioMed Central Ltd
16.02.2023
BioMed Central BMC |
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| Abstract | Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC.
We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity.
Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden.
We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. |
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| AbstractList | Background Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. Methods We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. Results Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. Conclusion We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. Keywords: SARS-CoV-2, Post-acute sequelae, Immune activation, Serological response, Anti-spike antibody Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. Abstract Background Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. Methods We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. Results Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. Conclusion We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. BackgroundIndividuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC.MethodsWe prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity.ResultsIndividuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden.ConclusionWe found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention. |
| ArticleNumber | 97 |
| Audience | Academic |
| Author | Le, Catherine N Sobhani, Kimia Sterling, Carina Frias, Edwin C Weber, Brittany Cheng, Susan Driver, Matthew Masoom, Hibah Zabner, Rachel Pedraza, Isabel Wynter, Timothy Khuu, Briana Kwan, Alan C Torossian, Mariam Ebinger, Joseph E Hoang, Amy Prostko, John C Joung, Sandy Oft, Jillian Goldzweig, Caroline Liu, Yunxian Fert-Bober, Justyna Wu, Min Barajas, Denisse Claggett, Brian L Tran, Teresa Botting, Patrick G Bravo, Michelle Sun, Nancy Sternbach, Sarah Stewart, James L Kao, Yu Hung Tang, Amber B Robertson, Jackie |
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Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 7 givenname: Sarah surname: Sternbach fullname: Sternbach, Sarah organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 8 givenname: Timothy surname: Wynter fullname: Wynter, Timothy organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 9 givenname: Amy surname: Hoang fullname: Hoang, Amy organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 10 givenname: Denisse surname: Barajas fullname: Barajas, Denisse organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 11 givenname: Yu Hung surname: Kao fullname: Kao, Yu Hung organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los 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Botting, Patrick G organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 18 givenname: Brian L surname: Claggett fullname: Claggett, Brian L organization: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA – sequence: 19 givenname: John C surname: Prostko fullname: Prostko, John C organization: Abbott Diagnostics, Abbott Park, IL, USA – sequence: 20 givenname: Edwin C surname: Frias fullname: Frias, Edwin C organization: Abbott Diagnostics, Abbott Park, IL, USA – sequence: 21 givenname: James L surname: Stewart fullname: Stewart, James L organization: Abbott Diagnostics, Abbott Park, IL, USA – sequence: 22 givenname: Jackie surname: Robertson fullname: Robertson, Jackie organization: Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 23 givenname: Alan C surname: Kwan fullname: Kwan, Alan C organization: Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 24 givenname: Mariam surname: Torossian fullname: Torossian, Mariam organization: Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 25 givenname: Isabel surname: Pedraza fullname: Pedraza, Isabel organization: Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 26 givenname: Carina surname: Sterling fullname: Sterling, Carina organization: Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 27 givenname: Caroline surname: Goldzweig fullname: Goldzweig, Caroline organization: Cedars-Sinai Medical Care Foundation, Cedars-Sinai Medical Center, Los Angeles, CA, USA – sequence: 28 givenname: Jillian surname: Oft fullname: Oft, Jillian organization: Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical 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Angeles, CA, USA. susan.cheng@cshs.org – sequence: 34 givenname: Catherine N surname: Le fullname: Le, Catherine N email: catherine.le@cshs.org organization: Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. catherine.le@cshs.org |
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| CitedBy_id | crossref_primary_10_1111_eci_14149 crossref_primary_10_3390_vaccines12060691 crossref_primary_10_3389_fimmu_2023_1223936 crossref_primary_10_1093_ofid_ofad364 crossref_primary_10_3390_idr15050058 |
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| Snippet | Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered... Background Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have... BackgroundIndividuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have... BACKGROUNDIndividuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have... Abstract Background Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals... |
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| SubjectTerms | ACE2 Adults Analysis Angiotensin Angiotensin-Converting Enzyme 2 Anti-spike antibody Antibodies Antibodies, Viral Binding Class switching Cohort analysis Comorbidity Comparative analysis Complications COVID-19 - prevention & control COVID-19 vaccines COVID-19 Vaccines - immunology Demographic variables Disease Progression Dosage and administration Drug dosages Enzymes Health aspects Health care Humans Humoral immunity Immune activation Immune response Immune response (humoral) Immune system Immunity Immunization Immunoglobulin G Immunoglobulin M Infections Longitudinal studies Missing data Nucleocapsids Patients Peptidyl-dipeptidase A Pharmaceutical industry Phenotypes Physiology, Pathological Plasma Post-Acute COVID-19 Syndrome - immunology Post-acute sequelae Regression analysis Review boards SARS-CoV-2 Serological response Serology Severe acute respiratory syndrome coronavirus 2 Vaccination Vaccines |
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| Title | Serological response to vaccination in post-acute sequelae of COVID |
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