Prediction of Effective Humoral Response to SARS-CoV-2 Vaccines in Healthy Subjects by Cortical Thickness of Post-vaccination Reactive Lymphadenopathy

Overview

Journal Eur Radiol

Specialty Radiology

Date 2023 May 4

PMID 37142867

Authors

Alba Cristina Igual-Rouilleault

Ignacio Soriano

Paola Leonor Quan

Gabriel Reina

Jose Luis Del Pozo

Alvaro Gonzalez

Leire Fernandez-Ciriza

Alejandro Fernandez-Montero

Luis Pina

Arlette Elizalde

Affiliations

Soon will be listed here.

Abstract

Purpose: To study the association between ultrasound cortical thickness in reactive post-vaccination lymph nodes and the elicited humoral response and to evaluate the performance of cortical thickness as a predictor of vaccine effectiveness in patients with and without a previous history of COVID-19 infection.

Methods: A total of 156 healthy volunteers were recruited and followed prospectively after receiving two COVID-19 vaccination doses using different protocols. Within a week after receiving the second dose, an axillary ultrasound of the ipsilateral vaccinated arm was performed, and serial post-vaccination serologic tests (PVST) were collected. Maximum cortical thickness was chosen as a nodal feature to analyze association with humoral immunity. Total antibodies quantified during consecutive PVST in previously-infected patients and in coronavirus-naïve volunteers were compared (Mann-Whitney U test). The association between hyperplastic-reactive lymph nodes and effective humoral response was studied (odds ratio). The performance of cortical thickness in detecting vaccination effectiveness was evaluated (area under the ROC curve).

Results: Significantly higher values for total antibodies were observed in volunteers with a previous history of COVID-19 infection (p < 0.001). The odds ratio associating immunized coronavirus-naïve volunteers after 90 and 180 days of the second dose with a cortical thickness ≥ 3 mm was statistically significant (95% CI 1.52-6.97 and 95% CI 1.47-7.29, respectively). The best AUC result was obtained comparing antibody secretion of coronavirus-naïve volunteers at 180 days (0.738).

Conclusions: Ultrasound cortical thickness of reactive lymph nodes in coronavirus-naïve patients may reflect antibody production and a long-term effective humoral response elicited by vaccination.

Clinical Relevance Statement: In coronavirus-naïve patients, ultrasound cortical thickness of post-vaccination reactive lymphadenopathy shows a positive association with protective antibody titers against SARS-CoV-2, especially in the long term, providing new insights into previous publications.

Key Points: • Hyperplastic lymphadenopathy was frequently observed after COVID-19 vaccination. • Ultrasound cortical thickness of reactive post-vaccine lymph nodes may reflect a long-term effective humoral response in coronavirus-naïve patients.

References

Pal I, Ramsey J . The role of the lymphatic system in vaccine trafficking and immune response. Adv Drug Deliv Rev. 2011; 63(10-11):909-22. DOI: 10.1016/j.addr.2011.05.018. View

Lederer K, Castano D, Gomez Atria D, Oguin 3rd T, Wang S, Manzoni T . SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation. Immunity. 2020; 53(6):1281-1295.e5. PMC: 7680029. DOI: 10.1016/j.immuni.2020.11.009. View

Igual-Rouilleault A, Soriano I, Quan P, Fernandez-Montero A, Elizalde A, Pina L . Unilateral axillary adenopathy induced by COVID-19 vaccine: US follow-up evaluation. Eur Radiol. 2021; 32(5):3199-3206. PMC: 8520081. DOI: 10.1007/s00330-021-08309-7. View

Yeahia R, Schefflein J, Chiarolanzio P, Rozenstein A, Gomes W, Ali S . Brain MRI findings in COVID-19 patients with PRES: A systematic review. Clin Imaging. 2021; 81:107-113. PMC: 8519663. DOI: 10.1016/j.clinimag.2021.10.003. View

Ozutemiz C, Krystosek L, Church A, Chauhan A, Ellermann J, Domingo-Musibay E . Lymphadenopathy in COVID-19 Vaccine Recipients: Diagnostic Dilemma in Oncologic Patients. Radiology. 2021; 300(1):E296-E300. PMC: 7909072. DOI: 10.1148/radiol.2021210275. View

Hao M, Edmonds C, Nachiappan A, Conant E, Zuckerman S . Management Strategies for Patients Presenting With Symptomatic Lymphadenopathy and Breast Edema After Recent COVID-19 Vaccination. AJR Am J Roentgenol. 2021; 218(6):970-976. DOI: 10.2214/AJR.21.27118. View

Becker A, Perez-Johnston R, Chikarmane S, Chen M, El Homsi M, Feigin K . Multidisciplinary Recommendations Regarding Post-Vaccine Adenopathy and Radiologic Imaging: Scientific Expert Panel. Radiology. 2021; 300(2):E323-E327. PMC: 7909071. DOI: 10.1148/radiol.2021210436. View

Granata V, Fusco R, Setola S, Galdiero R, Picone C, Izzo F . Lymphadenopathy after Covid-19 Vaccine: Preliminary Ultrasound Findings. Biology (Basel). 2021; 10(3). PMC: 8001230. DOI: 10.3390/biology10030214. View

Shin M, Hyun C, Choi Y, Choi J, Lee K, Cho Y . COVID-19 Vaccination-Associated Lymphadenopathy on FDG PET/CT: Distinctive Features in Adenovirus-Vectored Vaccine. Clin Nucl Med. 2021; 46(10):814-819. PMC: 8411598. DOI: 10.1097/RLU.0000000000003800. View

10.

Magni V, Cozzi A, Schiaffino S, Colarieti A, Sardanelli F . Artificial intelligence for digital breast tomosynthesis: Impact on diagnostic performance, reading times, and workload in the era of personalized screening. Eur J Radiol. 2022; 158:110631. DOI: 10.1016/j.ejrad.2022.110631. View

11.

Shirone N, Shinkai T, Yamane T, Uto F, Yoshimura H, Tamai H . Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination. Ann Nucl Med. 2012; 26(3):248-52. DOI: 10.1007/s12149-011-0568-x. View

12.

Thomassen A, Nielsen A, Gerke O, Johansen A, Petersen H . Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination. Eur J Nucl Med Mol Imaging. 2011; 38(5):894-8. DOI: 10.1007/s00259-011-1729-9. View

13.

Panagiotidis E, Exarhos D, Housianakou I, Bournazos A, Datseris I . FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1). Eur Radiol. 2010; 20(5):1251-3. DOI: 10.1007/s00330-010-1719-5. View

14.

Coates E, Costner P, Nason M, Herrin D, Conant S, Herscovitch P . Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses. Clin Nucl Med. 2017; 42(5):329-334. DOI: 10.1097/RLU.0000000000001603. View

15.

Burger I, Husmann L, Hany T, Schmid D, Schaefer N . Incidence and intensity of F-18 FDG uptake after vaccination with H1N1 vaccine. Clin Nucl Med. 2011; 36(10):848-53. DOI: 10.1097/RLU.0b013e3182177322. View

16.

Pani A, Cento V, Vismara C, Campisi D, DI Ruscio F, Romandini A . Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe-short- And long-term Immune reSponSe evAluatioN in health Care workErs. Mayo Clin Proc. 2021; 96(12):2966-2979. PMC: 8403667. DOI: 10.1016/j.mayocp.2021.08.013. View

17.

Caimi B, Franzetti M, Velleca R, Lai A, Gatti A, Rossi P . Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention. BMC Geriatr. 2022; 22(1):191. PMC: 8908300. DOI: 10.1186/s12877-022-02884-0. View

18.

Fernandez-Ciriza L, Gonzalez A, Del Pozo J, Fernandez-Montero A, Carmona-Torre F, Carlos S . Humoral and cellular immune response over 9 months of mRNA-1273, BNT162b2 and ChAdOx1 vaccination in a University Hospital in Spain. Sci Rep. 2022; 12(1):15606. PMC: 9546941. DOI: 10.1038/s41598-022-19537-2. View

19.

Thorne L, Bouhaddou M, Reuschl A, Zuliani-Alvarez L, Polacco B, Pelin A . Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2021; 602(7897):487-495. PMC: 8850198. DOI: 10.1038/s41586-021-04352-y. View

20.

Igual-Rouilleault A, Soriano I, Elizalde A, Quan P, Fernandez-Montero A, Sobrido C . Axillary lymph node imaging in mRNA, vector-based, and mix-and-match COVID-19 vaccine recipients: ultrasound features. Eur Radiol. 2022; 32(10):6598-6607. PMC: 9098792. DOI: 10.1007/s00330-022-08846-9. View