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Publications

Journal Article Epublish 9 citations

PubMed: 36797666 DOI: 10.1186/s12879-023-08060-y

Serological response to vaccination in post-acute sequelae of COVID.

BMC Infect Dis 23(1):97

Authors: Sandy Joung, Brittany Weber, Min Wu, Yunxian Liu, Amber B Tang, Matthew Driver, Sarah Sternbach, Timothy Wynter, Amy Hoang, Denisse Barajas, Yu Hung Kao, Briana Khuu, Michelle Bravo, Hibah Masoom, Teresa Tran, Nancy Sun, Patrick G Botting, Brian L Claggett, John C Prostko, Edwin C Frias, James L Stewart, Jackie Robertson, Alan C Kwan, Mariam Torossian, Isabel Pedraza, Carina Sterling, Caroline Goldzweig, Jillian Oft, Rachel Zabner, Justyna Fert-Bober, Joseph E Ebinger, Kimia Sobhani, Susan Cheng, Catherine N Le

Affiliations

  • Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
  • David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • Abbott Diagnostics, Abbott Park, IL, USA.
  • Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Cedars-Sinai Medical Care Foundation, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Department of Pathology and Laboratory Medicine, Cedars- Sinai Medical Center, Los Angeles, CA, USA.
  • Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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.

MeSH

Immunity, Humoral, Vaccines, Vaccination, Immunity, Immunoglobulin Class Switching

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