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. 2024 Aug 12;22(1):755.
doi: 10.1186/s12967-024-05556-2.

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

Ruggiero Alessandra #  1 , Caldrer Sara #  2 , Pastori Claudia  3 , Gianesini Natasha  1 , Cugnata Federica  4 , Brombin Chiara  4 , Fantoni Tobia  1 , Tais Stefano  2 , Rizzi Eleonora  2 , Matucci Andrea  2 , Mayora-Neto Martin  5 , Uberti-Foppa Caterina  6 , Temperton Nigel  5 , Di Serio Mariaclelia Stefania  4 , Lopalco Lucia #  7 , Piubelli Chiara #  2
Affiliations

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

Ruggiero Alessandra et al. J Transl Med. .

Abstract

Background: A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022.

Methods: The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender.

Result: We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs. 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs. VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010).

Conclusions: Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies.

Keywords: COVID-19 disease severity; COVID-19 vaccine; Elderly; Immunological response; Non-vaccinated; Plasma cytokines; Pneumonia; SARS-CoV-2 variants; Th2.

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Conflict of interest statement

Authors have no interests to declare.

Figures

Fig. 1
Fig. 1
Levels of SARS-CoV-2 specific antibodies and neutralizing activity. The dashed lines represent the cutoff values. p-values correspond to the comparison against the group VACno adjusted for age, gender and cancer. Tobit regression models for IgG-N (index), IgM-S (index) and IgG-RBD-S (BAU/mL). Linear regression models for the other outcomes. Full statistics report is available in Table 2 and Supplementary Table 2.
Fig. 2
Fig. 2
The relative frequencies of T Helper subpopulation and Treg lymphocyte in the different groups of subjects. Bar plot representing the median and 95% IC of Th cells relative frequencies in non vaccinated (VAC0) or vaccinated (VAC2 + 3) (a) or depending on the number of doses (b). Pie-chart showing the relative frequency of CD19 + B cells, CD8 and CD4 T-cells sub-populations on CD3 + lymphocytes in VAC0, VAC2 and VAC3 (c). p-alues were obtained using non-parametric Spearman test. Levels of statistical significance was set at p < 0.05
Fig. 3
Fig. 3
Spearman’s correlations between immunological responses in VACno (n = 17 in a) and VAC2 + 3 (n = 30 in b). The magnitude of each correlation is denoted with a colour, whereby the red colour indicates a positive correlation and the blue colour represents a negative correlation, such that the deeper the colour, the stronger the correlation. Levels of statistical significance with false discovery rate (FDR) correction are denoted as: p < 0.05, *p < 0.01, ***p < 0.001
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