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. 2023 Feb 16;23(1):97.
doi: 10.1186/s12879-023-08060-y.

Serological response to vaccination in post-acute sequelae of COVID

Sandy Joung #  1 , Brittany Weber #  2 , Min Wu  1 , Yunxian Liu  1 , Amber B Tang  3 , Matthew Driver  1 , Sarah Sternbach  1 , Timothy Wynter  1 , Amy Hoang  1 , Denisse Barajas  1 , Yu Hung Kao  1 , Briana Khuu  1 , Michelle Bravo  1 , Hibah Masoom  1 , Teresa Tran  1 , Nancy Sun  1 , Patrick G Botting  1 , Brian L Claggett  2 , John C Prostko  4 , Edwin C Frias  4 , James L Stewart  4 , Jackie Robertson  5 , Alan C Kwan  1 , Mariam Torossian  6 , Isabel Pedraza  6 , Carina Sterling  6 , Caroline Goldzweig  7 , Jillian Oft  5 , Rachel Zabner  5 , Justyna Fert-Bober  1 , Joseph E Ebinger  1 , Kimia Sobhani  8 , Susan Cheng #  9 , Catherine N Le #  10
Affiliations

Serological response to vaccination in post-acute sequelae of COVID

Sandy Joung et al. BMC Infect Dis. .

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.

Keywords: Anti-spike antibody; Immune activation; Post-acute sequelae; SARS-CoV-2; Serological response.

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Conflict of interest statement

JCP, ECF, and JLS work for Abbott Diagnostics, a company that performed the serological assays on the biospecimens that were collected for this study. The remaining authors have no potential conflicts of interests.

Figures

Fig. 1
Fig. 1
Pre- and post-vaccination IgG-S and IgG-N antibody levels in PASC. Individuals with PASC had a higher IgG-S antibody response to COVID vaccination compared to that seen in COVID-recovered or never-infected individuals (Panel A), suggesting more pronounced immune activation. Differences in vaccination provoked IgG-S response persisted over time despite PASC-affected and COVID-recovered individuals having similar levels of IgG-N antibody levels (Panel B), a marker of severity and timing of prior exposure to natural infection
Fig. 2
Fig. 2
Pre- and post-vaccination IgM-S antibody levels in PASC. In both never-infected and COVID-recovered individuals, IgM-S antibody levels were expectedly increased in the immediate post-vaccination period and then significantly decreased after 8 weeks (P ≤ 0.002 for within group comparisons between the time periods before and after 8 weeks). However, in the setting of PASC, IgM-S antibody levels were not significantly lower after compared to before 8 weeks from vaccination (P = 0.33). This finding was consistent with IgM-S levels being higher in COVID-recovered than PASC-affected individuals within 8 weeks after vaccination (P = 0.001) and then not significantly different between these groups beyond 8 weeks after vaccination (P = 0.12)
Fig. 3
Fig. 3
Pre- and post-vaccination ACE2 binding levels in PASC. Individuals with PASC compared to COVID-recovered individuals had similarly elevated ACE2 binding levels within 8 weeks following COVID vaccination. Notably, after 8 weeks, ACE2 binding levels remained higher in the PASC-affected compared to COVID-recovered individuals, mirroring results of IgG-S levels assessed during the same time period
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