The Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination and Infection on Neutralizing Antibodies: A Nation-wide Cross-sectional Analysis.

BACKGROUND: Neutralising antibodies (nAbs) play a critical role in the protection against severe COVID-19. In the era of vaccine boosters and repeated SARS-CoV-2 outbreaks, identifying individuals at risk represents a public health priority. METHODS: Relying on the Monaco COVID Public Health Programme, we evaluated nAbs from July 2021-June 2022 in 8,080 SARS-CoV-2 vaccinated and/or infected children and adults, at their inclusion visit. We stratified by infection status and investigated variables associated with nAbs using a generalised additive model. RESULTS: Infected and vaccinated participants had high and consistent nAbs (>800 IU/mL), which remained stable over time since injection, regardless of the number of vaccine doses, body mass index, sex, or age. By contrast, uninfected participants showed larger variability (two doses [V2] median 157.6; interquartile range [IQR] 43.3-439.1 IU/mL) versus three doses [V3] median 882.5; [829.5-914.8] IU/mL). NAbs decreased by 20% per month after V2 (adjusted ratio 0.80; 95%CI [0.79-0.82]), but remained stable after V3 (adjusted ratio 0.98; 95%CI [0.92-1.05]). CONCLUSIONS: Hybrid immunity provided stable, high and consistent nAbs over time. The benefit of boosters was marked to restore decaying nAbs in uninfected participants. NAbs could identify individuals at risk of severe COVID-19 and provide more targeted vaccine boosters' campaigns.

Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow.

Resting platelet adhesion to inflammatory vascular endothelium is thought to play a causal role in secondary thrombus formation or microcirculatory disturbance after vessel occlusion. However, though adhesion receptors involved in platelet-matrix interactions have been extensively studied, the molecular mechanisms involved in platelet-endothelium interactions are incompletely characterized and have been mainly studied under static conditions. Using human platelets or platelets from wild-type and CD47-/- mice in whole blood, we demonstrated that at low shear rate, CD47 expressed on human and mouse platelets significantly contributes to platelet adhesion on tumor necrosis factor-alpha (TNF-alpha)-stimulated vascular endothelial cells. Using the CD47 agonist peptide 4N1K and blocking monoclonal antibodies (mAbs), we showed that CD47 binds the cell-binding domain (CBD) of endothelial thrombospondin-1 (TSP-1), inducing activation of the platelet alphaIIbbeta3 integrin that in turn becomes able to link the endothelial receptors intercellular adhesion molecule 1 (ICAM-1) and alphavbeta3. Platelet CD36 and GPIbalpha are also involved because platelet incubation with blocking mAbs directed against each of these 2 receptors significantly decreased platelet arrest. Given that anti-CD47 treatment of platelets did not further decrease the adhesion of anti-CD36-treated platelets and CD36 is a TSP-1 receptor, it appears that CD36/TSP-1 interaction could trigger the CD47-dependent pathway. Overall, CD47 antagonists may be potentially useful to inhibit platelet adhesion on inflamed endothelium.