ABSTRACT
Background: SARS-COV2 infection is associated with inflammation, hypercoagulability and endothelial damage. Anti-SARS-COV2 vaccines have radically changed the course of the pandemic, however, reports on rare thrombotic events raise concern in the scientific community and the general population. Aims: In a prospectively enrolled cohort of adult subjects undergoing mRNA or adenovirus vector vaccination, we wanted to longitudinally evaluate the changes in levels of hemostatic biomarkers (i.e. activation of blood coagulation and perturbance of endothelium and fibrinolysis), together with the serological response, and occurrence of manifest thrombotic complications. Methods: Peripheral venous blood samples were collected at enrollment (day 0, D0) before the 1st vaccine dose, and on 15 (D15), 60 (D60), 90 (D90) and 180 (D180) days after the 1st dose. At each time point, hemostatic markers (i.e., fibrinogen, D-dimer, FVIII, von Willebrand Factor [vWF] antigen and activity, F1+2, thrombomodulin, protein C, protein S, FXIII, tPA, and PAI-1), and anti-Spike receptor-binding-domain protein (anti-S/RBD) IgG were measured. Follow up is currently continuing. Results: Fifty-three subjects (57% males) with a median age of 50 years (range 23-86) were enrolled into the study and followed-up for 6 months: 36 (68%) received BNT162b2, 6 (11%) mRNA-1273, and 8 (15%) ChAdOx1 nCoV-19 vaccines, in 2 doses over 21, 30 and 77 days, respectively;while 3 (6%) subjects received Ad26.COV2.S as single shot. Twenty individuals (38%) reported previous history of COVID-19, with a mean time from infection to vaccination of 10 months (4-18);only 1 required Hospitalization. Nine subjects presented cardiovascular risk factors and 4 a prior, non-active, cancer;3 were on anticoagulation for atrial fibrillation. The evaluation of the hemostatic biomarkers at the different time points showed variations in some of the parameters evaluated, with median values remaining within normal range levels. Specifically, compared to baseline, we observed a significant increase in thrombomodulin at D90 (p=0.001) and D180 (p=0.03), in parallel to a significant decrease in fibrinogen (D60), vWFAg (D60 and D180), FVIII (D60, D90 and D180), and TPA (D60 and D90) levels. The reduction of these biomarkers was particularly evident in individuals with a history of COVID-19. Of interest, this group of subjects was also characterized by significantly lower levels of PAI-1 both at baseline (7.18 ng/mL vs 17.53 ng/mL;p<0.0001), and at other time points (p<0.0001), and by an increase in F1+2 at D90 (p=0.02). The association between lower baseline PAI-1 levels with history of COVID-19 was confirmed by linear regression analysis (B= -10.351, p=0.013), and was independent by the time of infection resolution. Notably, no differences were observed in the hemostatic biomarkers according to vaccine types. All subjects positively responded to vaccination with a significant increase in anti-S/RBD IgG from baseline (D0) to each time point, especially COVID-19 subjects (D15, D60, and D90:p<0.0001;D180:p=0.031). No thrombotic or cardiovascular complications occurred during follow-up. Summary/Conclusion: No hypercoagulable state elicited by COVID-19 vaccination was observed, contrarily we detected an overall persistent reduction of coagulation activation over time. Subjects with previous SARS-COV2 infection had persistently low levels of PAI-1, supporting enhanced fibrinolysis activation. Compared with recent studies, our results provide a longer observation follow-up with all vaccine types and reassure on the safety of anti- SARS-COV2 vaccination.
ABSTRACT
Cancer patients exhibit an increased risk of venous thromboembolism (VTE), with VTE being the second leading cause of morbidity and mortality in these patients. The implementation of lockdowns following the COVID-19 pandemic has resulted in decreased mobility and delayed access to care, thus further increasing the susceptibility to VTE. Cancer patients may also be at a higher risk of SARS-CoV-2 infection and have been shown to be more likely to experience severe COVID-19 disease compared to patients without cancer. Given that both cancer and COVID-19 exhibit a hypercoagulable state, stasis of blood flow, and endothelial injury, cancer patients with COVID-19 constitute a vulnerable population with a high risk of thrombosis and bleeding. However, to date there are limited studies evaluating whether cancer patients infected with SARS-CoV-2 have a higher VTE incidence than COVID-19 patients without cancer, how to assess the risk of VTE, prophylaxis and treatment in this special population. Herein, we highlight the urgent need for studies in cancer patients with COVID-19 to ensure appropriate patient care and improve clinical outcomes. © 2022 The Authors
ABSTRACT
In March 2020, the World Health Organization declared a global pandemic due to an unprecedented health crisis by COVID-19. In the first stage, all the Countries applied strict policies to limit the spreading of the virus, significantly reducing the mobility trips (reduction over than the 90% for the public transport modes), and possibly by structurally modifying mobility habits of citizens. With respect to the study of how (and how much) mobility habits are changing during the pandemic, the new technologies and the real-time traffic data for monitoring the travel demand can play a significant role, and this research tries to contribute in this sense. Within this issue, the aim of this research was twice: i) verify the applicability of the Floating Car Data (FCD) for the origin-destination (OD) car trips (OD matrices) estimation, proposing an ad-hoc methodology for the scope;ii) estimating and comparing the OD car trips before and during COVID-19 pandemic within the Campania Region in south of Italy, investigating both seasonal and yearly impacts of the pandemic on the mobility habits (e.g. lock-down periods vs. recovery periods;summer vs. winter periods). Estimated results confirm the ability of FCDs to reproduce OD car trips. With respect to the impacts produced by the pandemic on car mobility, the estimation results underline that during the periods of the main mobility restrictions, the structure of the regional demand has significantly changed with respect to a pre-pandemic period: extra-provincial car trips have decreased (between 23% and 42%) than the intra-provincial ones, which have even increased (up to +5%);the distance travelled was reduced up to the 24%. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
Introduction: Severe COVID-19 patients present with a hypercoagulable state, complement activation and endothelial perturbation, which result from an excessive inflammatory response. Thromboinflammation is one important mechanism underlying the COVID-19-associated coagulopathy and the increased risk of thrombosis. Bergamo city is one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting convalescent COVID-19 patients, in a program of selection of candidates for convalescent plasma donation. In a large cohort of convalescent COVID-19 patients, we aimed to characterize markers of coagulation activation and endothelial perturbation, in order to explore whether the COVID-19-related hemostasis activation might persist afterwards and evaluate its possible association with the degree of severity of the previous infection, and/or with demographic characteristics, or anti-SARS-CoV-2 antibody levels. Methods: In 392 convalescent COVID-19 patients (216M/176F, median age: 46 years) plasma levels of fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, von Willebrand factor (vWF), prothrombin fragment F1+2 were measured at the recruitment, i.e. 1-5 months from recovery. Samples were tested for the anti-SARS-CoV-2 antibodies, including anti-S IgG (Anti-S Ab) and anti-N IgG (Anti-N Ab) antibodies at enrollment and at each scheduled subsequent visits. Results: Levels of fibrinogen, D-dimer, von Willebrand factor, protein S and protein C were significantly higher (p<0.05) in patients who were hospitalized for severe COVID-19 as compared to patients who were treated at home. There was no correlation between levels of coagulation biomarkers and days from end of symptoms. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab (p<0.001). Among hemostatic biomarkers, fibrinogen (p<0.01) and vWF (p<0.05) independently predict high levels of anti-S Ab. In particular, vWF levels positively correlated with anti-S Ab levels (vWFantigen r=0.188;vWF-activity r=0.241 and vWF-RiC of r=0.223, p<0.01). Evaluation of anti-SARS-CoV2 antibody levels at different time points during follow up revealed that 30% of patients displayed high levels of anti-S Ab until more than 8 months from the end of symptoms. Conclusions: Convalescent patients, with a history of severe COVID-19 had a persistent endothelium activation, despite of disease clinical remission even after 9 months from end of symptoms. Furthermore, fibrinogen and vWF levels predicted high levels of Anti-S Ab. Among demographic characteristics, gender, age and severe disease can be predictors of increased antibody response. These findings suggest that inflammation, coagulation and endothelial dysfunction may persist after recovery and may explain the findings of persistent clinical symptoms reported in these patients after healing from COVID-19.
ABSTRACT
[Formula presented] Introduction: Patients (pts) with immune thrombotic thrombocytopenic purpura (iTTP) are at high risk of severe COVID-19, therefore protection from SARS-CoV-2 by vaccination is particularly relevant in this setting, although concerns may exist on possible adverse reactions or disease relapse after vaccination. In this study, in a group of iTTP pts who received in-hospital COVID-19 vaccination in a special program for ‘fragile patients’, we prospectively evaluated over time the antibody response, the clinical and laboratory disease parameters and hemostatic biomarker levels. Methods: Twelve iTTP pts in clinical remission and regularly followed-up in our Center were enrolled in April 2021, all of them received 2 doses of BNT162b2 vaccine (Pfizer-BioNTech) over 21 days, and were followed-up for clinical and laboratory testing for 60 days. Blood samples were collected at enrollment (day 0, D0) before the 1 st vaccine dose;on day 21 (D21) before the 2 nd dose;and on day 60 (D60) after the 1 st dose. Blood cell counts, anti-Spike receptor-binding-domain protein (anti-S/RBD) IgG, ADAMTS-13 activity, and anti-ADAMTS-13 IgG (chromogenic assay and ELISA), were measured at each time point. Additionally, an extensive study of hemostatic markers (i.e. FVIII, von Willebrand Factor (vWF) antigen and activity, fibrinogen, D-dimer, tPA, PAI, and F1+2) was performed. Follow up is currently continuing. Results: Median age of our cohort was 65 years with M/F ratio of 4/8. Median time since last acute iTTP episode was 40 months, median follow up of the cohort was 71 months (95% CI 30-126). All pts were in clinical remission, except one patient (P1) who had an iTTP relapse after contracting SARS-CoV-2 infection, in Dec 2020, and was on low-dose steroids on D0. One patient (P2) had an ADAMTS-13 relapse in Jan 2021, and received pre-emptive rituximab. No other pts were on immunosuppressive therapy. Concerning the status of ADAMTS-13 activity on D0, 6 pts showed normal levels (>50%), while 5 had a moderate (50-20%) and 1 a complete (<10%) ADAMTS-13 deficiency. This latter patient (P3) had normal ADAMTS-13 activity before the pandemic. All patients were negative for anti-ADAMTS-13 inhibitor. Further, on D0, the anti-S/RBD IgG testing was positive in 3/12 pts (median 704,1 AU/mL), due to symptomatic infection in 1 case (P1), and asymptomatic in 2 (P3 and 1 pt with ADAMTS-13 activity of 54%, P4). The study of hemostatic markers on D0 showed an increase in median levels of FVIII and vWF antigen and activity. These parameters were altered in 7/12, 11/12 and 8/12 pts, respectively. Fibrinogen and D-dimer were increased in 3/12 and 2/12, respectively. Notably, P1, P3 and P4 presented the highest levels of FVIII and vWF antigen, associated with high levels of vWF activity in P1 and P3 (mean 233%);moreover, P3 showed higher levels of D-dimer (708 ng/mL) and tPA (13 ng/ml). After the 2 doses of BNT162b2, no significant clinical side effects were reported, and no changes in platelet counts. ADAMTS-13 activity and inhibitors did not significantly change on D21 and D60. A complete ADAMTS-13 activity deficiency persisted in P3 on D21 and D60, associated with anti-ADAMTS-13 IgG titer >15 U/ml, despite clinical remission. Overall, a significant increase in anti-S/RBD IgG level was observed on D21 (p = 0.0005) and D60 (p = 0.0005). Remarkably, only P2 did not show an increase in anti-S/RBD IgG titer after both doses of BNT162b2. Median levels of FVIII and vWF antigen did not significantly change during follow up, while increased vWF activity was seen on D60 (p = 0.05). Fibrinogen levels were stable, and an increase in D-dimer (>1000 ng/mL both on D21 and D60) was seen in P3. There were no changes in the other hemostatic parameters, and no thromboses were observed. Conclusions: In our cohort of iTTP pts, COVID-19 was associated with 1 clinical and 1 ADAMTS-13 relapse. Our data show that SARS-CoV-2 vaccination was effective in inducing an antibody response in all but one patient who received rituximab within 3 months before vaccinat on, confirming recent findings. Overall, vaccination had no relevant impact on the hemostatic profile of our pts, and did not appear to be a driver of iTTP relapses. However, anti-SARS-CoV-2 antibodies monitoring in iTTP pts may be useful after vaccination, as currently it is unknown how long the antibody titer may persist. Although small, this study is in favor of efficacy and safety of mRNA vaccines in pts with iTTP. Disclosures: Falanga: Bayer: Honoraria;Sanofi: Honoraria;Leo Pharma: Honoraria;Pfizer: Honoraria.
ABSTRACT
This article is a reflection by Psicologi per i Popoli - Campania's team about the intervention of Protezione Civile Campania at Ospedale del Mare Covid Center in Naples as a response to the Afghan emergency in Summer 2021. It is aimed at sharing some theoretical premises and some practical instruments adopted to provide refugees with psychological support. This is an opportunity to enhance our experience in the field and propose an intervention protocol and good practice for similar interventions. The article addresses the historical and cultural issues that led to this humanitarian crisis and how the team of emergency psychologists intervened to provide psychological first aid. The intervention was carried out according to the IASC guidelines with the primary objective of promoting an immediate and long-term state of safety, providing physical and emotional comfort. Where necessary it involved the use of techniques for the emotional stabilization of people overwhelmed by emotions and disoriented, preventing post-traumatic disorders in the medium and long term.
ABSTRACT
Background: Hospitalised COVID-19 pneumonia patients are characterised by the occurrence of a hypercoagulable state associated to a high risk of thromboembolic events. The main laboratory findings of this coagulopathy include D-dimer increase, mild thrombocytopenia, prolonged PT, and increase endothelial activation biomarkers (vWF, thrombomodulin). No data are available about coagulation profile in patients presenting with an acute coronary syndrome (ACS) combined with SARS-CoV-2 infection. Purpose: In this prospective study, we aimed to evaluate the contribute of concomitant SARS-CoV-2 infection to the haemostatic system derangement (i.e., from endothelial cell activation to fibrinolytic phase) observed in patients presenting with ACS. Further, the role of haemostatic biomarkers (HB) for in-hospital mortality risk prediction was also explored. Methods: Consecutive patients admitted to our hospital for ACS at peak intensity of local pandemia were enrolled into this study. At admission, all patients underwent routine blood examinations with blood count, serum biochemical tests and an extensive coagulation profiling. Data from coronary angiography and percutaneous coronary intervention (PCI), when performed, were collected. In-hospital major adverse cardio and cerebrovascular events -MACCEs- (total and cardiovascular death, stroke, systemic or pulmonary embolism, re-MI and bleedings) are reported. Results: A total of 99 (76M/23F) consecutive patients with a median age of 66.7 (±12.1) were enrolled. According to nasal swab, 24 patients were SARS-CoV-2 positive and 75 negative. The two groups, similar in age, sex and cardiovascular risk factors, significantly differed in presenting symptoms (p<.001) and radiological signs of pneumonia (p<.0001). At admission, there were no differences in routine laboratory values between groups. Differently, analysis of the HB showed significantly higher values of D-dimer, vWF antigen, vWF activity and vWF;RiCof, t-PA and PAI-1 and lower levels of ADAMTS-13 in the positive group. Furthermore, among ACS patients, both STEMI and NSTEMI subjects, positive for SARS-CoV-2, had significantly higher plasma values of all the HB compared to the respective negative counterparts, with SARS-CoV-2 positive STEMI subjects displaying the highest values. When performed, PCI finished more frequently with a final TIMI flow <3 (p=.004) in positive patients. The in-hospital rate of MACCEs was 24% (24/99 patients) with a higher (p<.0001) prevalence in SARS-Co-V2 positive group. Cardiovascular mortality accounted for the majority of deaths (8/10;p=.019). At multivariable analysis, we identified dyspnoea at presentation, vWF antigen and leukocyte values as independent risk factors for in-hospital death. Conclusions: In patients presenting with ACS combined with SARS-Cov- 2 infection an additional HB asset derangement with stronger endothelial cell activation occurs which negatively impact the outcome, regardless of the invasive treatment.
ABSTRACT
Background: Hypercoagulability, complement activation and endothelial perturbation characterize sever COVID-19. After disease remission, a proportion of convalescent subjects still experience post-COVID-19 symptoms. No information is available on persistence of hemostatic alterations in this setting. Bergamo city, represents one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting CCP donors. Aims: In a large cohort of CCP donors, we aimed to characterize biomarkers of hypercoagulability and of endothelial perturbation in order to find associations with disease severity, demographic characteristics, and anti-SARS-CoV-2 antibody levels. Methods : Candidate CCP donors were tested for the anti-SARSCoV-2 antibodies, including anti-S IgG antibodies (Anti-S Ab) and anti-N IgG antibodies (Anti-N Ab). In addition, the following plasma biomarkers were assessed: fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, and von Willebrand factor (vWF). Results: 425 CCP candidates (275M/150F, age range 19-67 years) were admitted to donation. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab ( p <0.001). Among hemostatic parameters, levels of vWF antigen, vWF activity and protein C were significantly higher in CCP donors who had severe COVID-19 compared to donors who had non-severe COVID-19 ( p <0.001). Furthermore, vWF levels positively correlated with anti-S Ab levels (vWF-antigen r=0.216 vWF-activity r=0.257 and vWFRiCof r=0.226, p <0.01). Conclusions: Our data show that gender, age and severe disease can be predictors of an increased immunological response. Furthermore, convalescent subjects show a persistently high vWF levels, suggesting a persistence of the endothelial activation, despite of clinical disease remission.
ABSTRACT
Background : Endothelial damage and hypercoagulability are major players behind the hemostatic derangement in SARS-CoV-2 infection. Aims : In this prospective cohort study of COVID-19 patients, we aimed to assess the role of circulating endothelial activation/damage biomarkers in predicting in-hospital mortality. Methods : Clinical data of COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were analyzed. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, CRP and procalcitonin were assessed. Results : Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of Ddimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). Patients with a moderate and severe ARDS (i.e. PaO2/FiO2 ≤200%) have considerably higher vWF and sTM levels, and lower t-PA/PAI-1 values compared to patients in the mild ARDS group (i.e. PaO2/FiO2 >200%). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/ FiO2 were significantly associated with death. Using these variables, we generated a linear score with 3-risk groups (AUC 0.903) that provided a cumulative incidence of death of 0 % in the low-, 32% in the intermediate-, and 78% in the high-risk group ( P < 0.001). Conclusions : In conclusion, our study provides an extensive overview of the endothelial damage induced by SARSCoV-2 infection in hospitalized patients with virus-induced pneumonia and different degrees of disease severity. In addition, despite the small sample size and the need for the external validation, we could generate an accurate score based on circulating vWF to predicting mortality in severe COVID-19 patients.
ABSTRACT
Background: Severe COVID-19 is associated with a profound derangement of the hemostatic system characterized by hypercoagulability, complement activation and endothelial cell perturbation. After disease resolution, some convalescent subjects still experience post-COVID-19 symptoms. No information is available on persistence of hemostatic alterations in this setting. Bergamo city, represents one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in hyperimmune plasma collection from COVID-19 convalescent subjects. Aims: In this study, in a large cohort of convalescent donors of hyperimmune plasma, we aimed to characterize select hemostatic parameters of hypercoagulability and endothelial cell perturbation and their association with disease severity, demographic characteristics, and antibody levels. Methods: Recovered COVID-19 patients eligible to plasma donation were tested for the SARS-CoV-2 antibodies by the anti-N IgG SARSCoV- 2 antibodies (Abbott Laboratories, IL, USA, Anti-N Abs), and/or the anti-S IgG SARS-CoV-2 antibodies (Liaison-Diasorin, Sallugia-VC, Italy, Anti-S Abs), according to the manufacturer's instructions. Fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, and von Willebrand factor (vWF) were assessed. Results: 425 subjects have been included (275M/150F) with a median age of 48 years (range: 19-67 years). Among convalescent subjects admitted to the donation, male gender, age > 40 years, and previous hospitalization for COVID-19, were identified as independent predictive factors for significantly (p<0.001) higher levels of SARS-CoV-2 IgG (both anti-S and anti-N). Hemostatic parameters including fibrinogen, protein S, factor V, factor VIII, factor XIII, and D-dimer were not different between severe and non-severe COVID-19. Differently, convalescent subjects with previous severe COVID-19 showed significantly higher levels of vWF (124±40 vs 121±41 %, p<0.001) and PC (119±19 vs 109±19 %, p<0.001) compared with non-severe COVID-19 subjects. In addition, significant positive correlations were found between vWF levels and anti-S Abs (vWF antigen r=0.216;vWF activity r=0.257 and vWF RiCof r=0.226, p<0.01). Summary/Conclusion: Our data show that gender, age and severe disease can be potential predictors of an increased immunological response. Furthermore, convalescent subjects show a persistently high vWF levels, suggesting a persistence of the endothelial activation, despite of clinical disease remission.