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
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
HIV remains a major public health problem in Sub-Saharan Africa. About 54.5% of all people living with HIV live in Eastern and Southern Africa. There is no HIV vaccine or cure available yet despite ongoing research to develop one and uptake of vaccines is critical in the global society. It is imperative to describe the perceptions and experiences of the vaccines trial participants, as they may give lessons for COVID-19 vaccine development. A phenomenological qualitative study was conducted to describe the experiences of volunteers who participated in a phase I/II HIV vaccine trial in Tanzania. A purposive sample of 20 of the 60 trial participants was interviewed. Interviews were subjected to thematic-content analysis. The study showed that trial participation was driven by positive expectations related to health and the realization of the need for an effective vaccine to combat HIV. However, fear and concerns about the safety of the trial vaccine were the frequently reported challenges to participation. The significant others and community play an important role in trial participation. The success of a trial depends on direct and indirect participation in trials. Future vaccine trials must promote positive expectations for trial participation and address fears and concerns related to vaccine safety.
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.