Prediction of effective humoral response to SARS-CoV-2 vaccines in healthy subjects by cortical thickness of post-vaccination reactive lymphadenopathy.

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.

Axillary lymph node imaging in mRNA, vector-based, and mix-and-match COVID-19 vaccine recipients: ultrasound features.

OBJECTIVES: To assess ultrasound characteristics of ipsilateral axillary lymph nodes after two doses of four different COVID-19 vaccination protocols, to determine whether these parameters differed with age, and to describe how they changed on follow-up imaging. METHODS: A total of 247 volunteer employees from our center who had received two doses of COVID-19 vaccination were recruited and followed prospectively. Axillary ultrasound of the ipsilateral vaccinated arm was performed the week after receiving the second dose to analyze lymph node features (number, long-axis, cortical thickness, morphology, and vascular imaging). Axillary lymphadenopathy resulting from four vaccination protocols-mRNA (BNT162b2, mRNA-1273), ChAdOx1-S, and mix-and-match-was compared. Analysis was conducted using the Kruskal-Wallis test and post hoc analysis with Bonferroni corrections. Nodal reactogenicity was evaluated for two age groups: young (< 45 years old) and middle-aged ( ≥ 45 years old). All parameters were compared between both groups using an unpaired-sample Student t test. A p value < 0.05 was considered statistically significant. RESULTS: Significantly higher values for total number of visible nodes, cortical thickness, Bedi's classification (p < 0.001), and vascularity (p < 0.05) were observed in mRNA vaccine recipients compared to full ChAdOx1-S protocol recipients. Moreover, mix-and-match protocol recipients showed greater nodal cortical thickness and higher Bedi's classification than full ChAdOx1-S recipients (p < 0.001). Analyses between age groups revealed greater cortical thickness, Bedi's classification, and color Doppler signal in younger patients (p < 0.05). CONCLUSIONS: Nodal parameters of Bedi's classification and cortical thickness were more often increased in mRNA and mix-and-match vaccine recipients when compared to ChAdOx1-S vaccine alone, especially in younger patients. KEY POINTS: • Hyperplastic lymphadenopathy was observed more frequently in mRNA and mix-and-match vaccine protocols compared to full vector-based vaccination. • Higher values for cortical thickness, Bedi's classification, and color Doppler signal parameters were identified in younger patients. • Observed lymph node findings normalized in greater than 80% of patients by the third month following vaccination.

Unilateral axillary adenopathy induced by COVID-19 vaccine: US follow-up evaluation.

OBJECTIVES: This study was conducted in order to investigate COVID-19 vaccine influence on unilateral axillary lymph nodes, comparing nodal basal features with their characteristics after the first and second vaccination dose. METHODS: Ninety-one volunteer employees from our center who participated in the BNT162b2 (Pfizer-BioNTech) vaccination campaign were prospectively recruited. A total of three axillary ultrasound evaluations of the ipsilateral vaccinated arm were performed: before vaccination, the week after the first dose and the week after the second dose. The following findings were recorded: the total number of visible nodes, the maximum measurements of the diameter and cortex, Bedi's classification, and color Doppler evaluation. The collected data were compared using paired-sample Student's t-test for quantitative continuous variables and Wilcoxon rank-sum test for ordinal variables. Additional analyses were performed after classifying patients according to the previous history of COVID-19 disease. Differences among both groups were evaluated with the Mann-Whitney U test. Variables with a p value < 0.05 were considered statistically significant. RESULTS: Comparative analyses between the three US examinations showed a statistically significant augmentation of total visible nodes, maximum diameter, cortical thickness, grade of Bedi's classification, and Doppler signal (p < 0.001). Analyses between patients with and without previous COVID-19 infection showed a higher lymph node response in naïve patients compared to those who were previously infected. CONCLUSIONS: According to our results, both doses of COVID-19 vaccine induced an increase of all axillary lymph node parameters with statistically significant differences, especially in coronavirus-naïve patients. KEY POINTS: • Pfizer COVID-19 vaccine induces a high incidence of ipsilateral axillary lymphadenopathy. • US scan identified an increase of all lymph nodes parameters, especially in coronavirus-naïve patients.