ABSTRACT
Background: Nuclei acid-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalisation and death. As they were distributed for the first time on a large-scale population, the adenovirus-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between vaccination and platelet activation gained increasing attention. Aim(s): To compare the effect of mRNA-based and adenovirus-based vaccines on platelets of young healthy adults. Method(s): We prospectively enrolled 15 healthy volunteers (53% females) who received two doses of the mRNA-based vaccine BNT162b2, 21 days apart, and 25 healthy volunteers (64% females) that received one dose of the adenovirus-based vaccine, AZD1222, followed by one dose of BNT162b2 and we studied their platelet response before and after each dose of the vaccine (3 and 10 days post-injection). Result(s): Subjects receiving the AZD1222 vaccine experienced a transient but significant 20% decrease of the platelet count 3 days after the first injection, which was not detected after the first dose of BNT162b2. The BNT162b2, but not the AZD1222, vaccine was followed by increased plasmatic thrombopoietin concentration and mean platelet volume, indicative of higher platelet turnover. Three days after the AZD1222 injection, basal platelet integrin activation was elevated, but P-selectin exposure was unchanged. Conversely, the BNT162b2 vaccine induced a gradual increase in platelet P-selectin exposure and platelet-leukocyte aggregate formation, which correlated with the ability of the vaccines to evoke neutralizing antibodies against the Sars-COV- 2 spike protein. Moreover, three days after the AZD1222 injection we detected a transient 10-fold increase of the plasmatic concentration of IFN-gamma, while BNT vaccination induced a progressive increase of IL-1beta. Conclusion(s): Based on these observations we propose that the adenovirus-based vaccines, not the mRNA-based vaccines, transiently impair platelet count homeostasis. Future studies will investigate how these distinct vaccine vectors and inflammatory profiles affect platelet consumption and platelet production.
ABSTRACT
Background: A severe SARS-CoV-2 related immunopathology may be the driver cause underlying the deleterious clinical manifestations observed in COVID-19 patients. To identify possible tissue-specific immune responses patterns, a compartmental immunophenotyping analysis of CD4+ and CD8+ T lymphocytes and IFN response has been performed in SARS-CoV-2 infected subjects with acute respiratory distress syndrome. Methods: Bronchoalveolar lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) samples were collected from 13 SARS-CoV-2 infected subjects (9 males and 4 females) consecutively admitted to intensive care unit (ICU) of Policlinico Umberto I, Sapienza University Hospital in Rome (Italy). The frequencies of CD4+, CD8+ T lymphocytes and those expressing immune activation markers (CD38, HLADR), naïve, central memory (CMEM), and effector memory (TEM) T cell subsets were evaluated in both anatomical sites by multiparametric flow cytometry. Gene expression levels of Interferon regulatory factor 7 (IRF7) and the Interferon Stimulated Gene 15 (ISG15) were evaluated in BAL and PBMC by Real-time PCR. Results: Critically SARS-CoV-2 infected patients exhibited a lung compartmentalization of CD8+ T cells (p=0.003), with a lower CD4/CD8 ratio in BAL compared to blood district (p<0.01). However, higher frequencies of CD8+ T cells were recorded in PBMC of female SARS-CoV-2 infected patients (p=0.04) and the same trend was observed in the lung compartment. By contrast, a trend of increasing CD4+ T cells frequencies was observed in BAL samples of male patients, as opposed to blood compartment. Additionally, an increased expression of immune activation markers CD38 and HLADR has been detected in BAL CD8+ T cells (p<0.01) as well as in blood CD4+ T cells (p=0.03). An increased frequency of CD4+ and CD8+ TEM cells has been documented in BAL of SARS-CoV-2 infected patients (p<0.05), as opposed to higher frequencies of CD4+ and CD8+ TCM cells recorded in the blood compartment (p<0.01). Notably, higher levels of ISG15 and IRF7 found in BAL were inversely associated to activated CD8+ T cell frequencies in the lung compartment compared to blood district (ISG15: r=-0.570, p<0.05) (IRF7: r=-0.683, p=0.01). Conclusion: Our findings provide new insight into a distinct T cells profile and IFN genes expression in the lung and in the blood compartment of SARS-CoV-2 infected patients, that might be highly relevant for the clinical course of COVID-19.