ABSTRACT
Background and aims: Relative Bradycardia (RB) is a poorly understood condition that refers to inappropriately low heart rate response to a given increase in body temperature. Dysfunctional crosstalk between the immune system and the autonomous nervous system has been advocated. It is most often observed in intracellular gram negative and parasitic infections, with a prevalence ranging between 15% and 20%. The aim of this study was to identify the prevalence, clinical determinants and significance of RB in patients hospitalized for SARS-CoV-2 infection and to evaluate its prognostic value for long-covid syndrome during follow-up. Method(s): We enrolled consecutive patients hospitalized for SARS-CoV-2 infection from March 2020 to April 2021. We collected clinical parameters including clinostatic and orthostatic blood pressure (BP) and heart rate (HR) at 1,3 and 5 minutes, oxygen saturation, body temperature (BT), routine blood tests, 12-lead ECG, and 48-h Holter ECG. At follow up, clinical symptoms were investigated by novel Malmo POTS Symptoms (MAPS) questionnaire. Result(s): Total population included 269 inpatients (mean age 67+/-17 years, 59% male).Of these, 30 (11%) presented with sinus bradycardia and 37 (14%) RB. RB was more frequently observed in younger male patients with higher BT and heightened CRP levels. There were no significant correlations between BP and HR orthostatic changes and BR during hospital admission or during follow-up. No clinically relevant arrhythmias were revealed during 48-hour ECG monitoring. After mean16-month follow-up, MAPS score was higher in patients with RB (30+/-19) compared to those without RB (18+/-21, p=0.001) during index hospital admission. Dizziness, palpitations and fatigue were more frequently reported in patients with RB(p<0.001). Conclusion(s): RB is not an uncommon condition during acute COVID-19. SARS-CoV-2 inpatients who presented RB during index hospitalization showed a higher symptom burden during follow-up, as recorded by MAPS score. Further studies are needed to clarify the clinical significance of RB and its value to predict post-acute sequelae of COVID-19. (Figure Presented).
ABSTRACT
Background: COVID-19 is associated with an increased risk of venous thrombosis, even when patients are on standard-dose antithrombotic prophylaxis. Hence, the identification of biomarkers of thrombosis helps tailoring dosage of antithrombotic prophylaxis. D-dimer has been extensively employed as a biomarker and cut-off values at hospital admission have been proposed to stratify the risk of thrombosis and make decision on prophylaxis. However, D-dimer measurement is not standardized, and it is unknown if the cut-off values used for decision making can be used interchangeably between methods. Aim(s): To assess for concordance of results obtained with different commercially available laboratory methods measuring D-dimer. Method(s): Plasma samples collected from COVID-19 patients at the Hospital of Cremona were evaluated for D-dimer with three widely used immunoturbidimetric methods (Liatest D-di, Stago, Asnieres, France;D-dimer HS 500, Werfen, Orangeburg, NY;Innovance D-dimer, Siemens, Marburg, Germany). Result(s): A total of 87 COVID-19 patients [54 male and 33 female, median age of 73 years (range 28-98)] were enrolled in the study. No significant differences were found between mean D-dimer concentrations obtained with the three methods even when stratifying D-dimer levels in 4 groups (<1000, 1000-2000, 2000-5000, >5000 ng/mL) (Figure 1). The three methods showed substantial result agreement [Stago-vs- Werfen and Siemens-vs- Stago (Cohen's kappa coefficient of 0.760 and 0.699, respectively)] to an almost perfect agreement [Siemens-vs- Werfen (Cohen's kappa coefficient of 0.811)], with a p-value < 0.001. Results from the three methods showed a good linear correlation (Rho = 0.94) (Figure 2). Conclusion(s): The relatively good concordance of D-dimer results among the three investigated methods indicates that D-dimer cut-off values could be used interchangeably regardless of the method used for testing. The results pave the way to clinical trials aimed to assess the value of D-dimer as a biomarker to make decision on the intensity of antithrombotic prophylaxis in COVID-19 patients. (Figure Presented).
ABSTRACT
Background: Cancer patients (pts) have higher risk of serious COVID-19 symptoms, morbidity and mortality than general population. SARS-CoV-2 vaccine trials excluded patients with metastatic cancer or undergoing immunosuppressive therapies;therefore, the effectiveness of vaccines are unknown in this population. Hence, there is an urgent need to understand the correlation between cancer type, its treatment and vaccine efficacy. Material and Methods: This is a prospective study conducted by the Oncology Unit of Cremona Hospital, enrolling pts from Oncology, Hematology, Radiotherapy and Palliative Care divisions. The trial aims to evaluate effectiveness of mRNA vaccines [BNT162b2 (Pfizer) and mRNA-1273 (Moderna)], incidence of symptomatic COVID-19 infection, antibodies (Abs) response in a consecutive population of 300 cancer pts, undergoing antiblastic therapies, starting from March 2021. Primary endpoint: Number of symptomatic pts affected by COVID-19, diagnosed 7-60 days after the 2nddose of vaccines. Secondary endpoints: Abs variation at different timepoints;duration of abs;correlation between effectiveness of vaccines and antiblastic treatments. Statistical Analysis: The primary objective will be tested by non-inferiority one-single proportion test, compared with the value of 95% observed in the vaccine registration trials. The hypothesis of vaccine inferiority in the trial population is rejected if a rate of protection conferred by the vaccine is observed in 89% of the sample size. Results: 356 patients received mRNA anti-COVID-19 vaccines. None of them reported symptomatic COVID-19 infection after vaccination. Whereas almost all patients (95.6%) with solid tumors developed an antibody response, only 77% of patients with hematological malignancy demonstrated anti-COVID-19 antibody production after vaccination. The different antiblastic treatments didn't have a significant impact on the antibody response. In particular, patients treated with immunotherapies and with chemotherapy developed antibodies against COVID-19 in 98% and 92% of cases, respectively. Conclusions: Vaccination against COVID-19 demonstrated to be effective and to prevent symptomatic COVID- 19 infection in patients with solid and hematological tumors during antiblastic treatment. The depth of antibody response resulted different between patients with solid and hematological malignancies. Different antiblastic therapies didn't significantly impact on the development of the antibody response.
ABSTRACT
Background : COVID-19 (Coronavirus Disease 2019) is associated with High rates of thrombosis in hospitalized patients leading to varying pharmacologic thromboprophylaxis use based on rapidly changing societal guidance, institutional protocols from local expertise, and geographic patterns of practice. Aims : To assess the efficacy and safety of enoxaparin in hospitalized patients with moderate to severe COVID-19 infection. Methods : Phase II single-arm interventional prospective study including all patients treated with the study drug and an observational prospective cohort study including all patients screened for receiving the study drug but not included in the phase II study. Each patient was followed-up for a minimum of 90 days after COVID19 diagnosis. Patients included in the interventional study received subcutaneous enoxaparin in a single daily dose of:60 mg once daily in case of body weight of 45 to 60 kg 80 mg per day in case of weight from 61 to 100 kg or 100 mg once daily in case of bodyweight >100 kg for 14 days, with dose adjustments on the basis of anti-factor Xa activity monitoring. Patients included in the observational cohort received standard thrombo-prophylaxis with subcutaneous enoxaparin 40 mg/die. Primary outcomes were all-cause in-hospital 30-day and 90 mortality rates. Secondary outcomes were the proportion of patients in the severe or critical stage of disease at the end of treatment, proportion of patients who developed major and non-major bleeding events and thromboembolic complications, time to first negative RT-PCR on nasofaringeal swab, reduction of viral load in blood. Results : Recruitment of 100 patients enrolled phase II single-arm interventional prospective study has been completed, while the recruitment of 200 patients in the observational prospective cohort study is ongoing. Conclusions : Full results will be available by June 2021.
ABSTRACT
Background: Cancer patients (pts) have higher risk of serious COVID-19 symptoms, morbidity and mortality than general population. SARS-CoV-2 vaccine trials excluded patients with metastatic cancer or undergoing immunosuppressive therapies;therefore, the effectiveness of vaccines are unknown in this population. Hence, there is an urgent need to understand the correlation between cancer type, its treatment and vaccine efficacy. Trial design: Methods: This is a prospective study conducted by the Oncology Unit of Cremona (Cr) Hospital, enrolling pts from Oncology, Hematology, Radiotherapy (RT) and Palliative Care divisions. The trial aims to evaluate effectiveness of mRNA vaccines [BNT162b2 (Pfizer) and mRNA-1273 (Moderna)], incidence of symptomatic COVID-19 infection, antibodies (Abs) response and onset of adverse events (AEs) in a consecutive population of 300 cancer pts, undergoing antiblastic therapies, starting from March 2021. A vaccination point was set up by Cr Hospital, dedicated to cancer pts treated with chemotherapy (CT), TKIs, RT, hormones. Only pts in follow-up or treated with adjuvant hormone are excluded. CT was suspended at least 5 days before and 3 days after vaccination;targeted therapy, immunotherapy and RT are not interrupted. Primary endpoint: Number of symptomatic pts affected by COVID-19, diagnosed 7-60 days after the 2nddose of vaccines. The infection is defined according to the FDA criteria combined with a positive nasopharyngeal swab. Secondary endpoints: Abs variation at different timepoints compared to baseline;vaccine-related adverse events;duration of abs, up to 12 months after 2nd dose;correlation between effectiveness of vaccines and antiblastic treatments, tumor burden, PS ECOG. Statistical analysis: The primary objective will be tested by non-inferiority one-single proportion test, compared with the value of 95% observed in the vaccine registration trials. The hypothesis of vaccine inferiority in the trial population is rejected if a rate of protection conferred by the vaccine is observed in 89% of the sample size. Results Preliminary results will be available in July 2021. Clinical trial identification: NCT04878796. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.