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1.
J Thromb Haemost ; 20(4): 961-974, 2022 04.
Article in English | MEDLINE | ID: covidwho-1626860

ABSTRACT

BACKGROUND: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known. OBJECTIVE: To identify features of the platelet-immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA-based COVID-19 vaccine (BNT162b2). METHODS: We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post-injection), in relation to the kinetics of the humoral response. RESULTS: Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled receptor CD31 (PECAM-1) compared to slow responders, and formed specific platelet-leukocyte aggregates, with B cells, just 3 days after the first dose, and with non-classical monocytes and eosinophils. CONCLUSION: We identified features of the platelet-immune crosstalk that are associated with the development of a rapid humoral response to an mRNA-based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.


Subject(s)
Blood Platelets/immunology , COVID-19 , Immunity, Humoral , Adult , Antibodies, Viral/blood , COVID-19/prevention & control , Female , Humans , Male , SARS-CoV-2
2.
Dermatol Ther ; 34(6): e15153, 2021 11.
Article in English | MEDLINE | ID: covidwho-1555455

ABSTRACT

An in-depth characterization of the incidence, morphology, and onset of COVID-19-vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID-19 vaccination-related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID-19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine-related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID-19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID-19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID-19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2
3.
J Thromb Thrombolysis ; 52(1): 105-110, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1002136

ABSTRACT

Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients.


Subject(s)
Blood Platelets/metabolism , COVID-19/blood , Platelet Aggregation , von Willebrand Factor/metabolism , Adult , Aged , Aged, 80 and over , Agglutination , Blood Platelets/virology , COVID-19/diagnosis , COVID-19/virology , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Platelet Function Tests , Protein Binding , SARS-CoV-2/pathogenicity , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/virology
4.
Dig Liver Dis ; 52(12): 1383-1389, 2020 12.
Article in English | MEDLINE | ID: covidwho-834313

ABSTRACT

The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice.


Subject(s)
Bacterial Translocation/immunology , COVID-19/immunology , Cytokine Release Syndrome/immunology , Gastrointestinal Microbiome/immunology , Intestinal Mucosa/metabolism , Lipopolysaccharides/metabolism , Liver/metabolism , Permeability , Alarmins/immunology , Alarmins/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Disease Progression , Humans , Immunity/immunology , Inflammation , Interleukin-6/immunology , Lipopolysaccharides/immunology , Liver/immunology , Lung/immunology , Lung/metabolism , Microbiota/immunology , Pathogen-Associated Molecular Pattern Molecules/immunology , Pathogen-Associated Molecular Pattern Molecules/metabolism , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism
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