High plasma levels of activated factor VII-antithrombin complex indicate increased tissue factor expression/activation in patients with COVID-19

Background: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), the causal agent of coronavirus disease 2019 (COVID-19), is associated with coagulation abnormalities, in which endothelial injury/dysfunction may be a key pathogenic mechanism. Endothelial dysfunction triggers tissue factor (TF) expression. Activated factor VII-antithrombin (FVIIa-AT) complex is a potential biomarker of prothrombotic diathesis reflecting FVIIa-TF interaction. Aim(s): To evaluate FVIIa-AT plasma levels in subjects with COVID-19 pneumonia. Method(s): FVIIa-AT plasma levels were assessed in 40 subjects (30 males and 10 females;64.8 +/- 12.3 years) admitted for COVID-19 pneumonia during the first pandemic wave in Italy (April 2020). FVIIa-AT levels were compared with those of two sex-and age-matched groups of hospitalized subjects without COVID-19, with or without laboratory signs of systemic inflammation. The concentration of FVIIa-AT was measured by ELISA on frozen citrate plasma samples. Data of coagulant activities of factor II (FII:c), factor V (FV:c), and factor VIII (FVIII:c) were available in a subgroup of subjects. Result(s): Hospitalized COVID-19 patients had FVIIa-AT levels significantly higher than sex-and age-matched no COVID-19 subjects (Table 1), either with or without inflammation (p = 0.013 and p = 0.017 by ANOVA with Tukey post-hoc comparison, respectively). No difference in FVIIa-AT levels was observed between no COVID-19 subjects with or without inflammation (p = 0.995). The association between COVID-19 and FVIIa-AT levels in the whole study sample remained significant by linear regression analysis adjusted for sex, age, C reactive protein, estimated glomerular filtration rate, fibrinogen, prothrombin time, and activated partial thromboplastin time (B coefficient 0.322 with standard error 0135, p = 0.019). In sub-analysis COVID-19 patients showed also lower FII:c, FV:c, and FVIII:c levels (Table 1). Conclusion(s): Our results indicate that SARS-CoV2 infection, at least during the first pandemic wave, was characterized by increased FVIIa-AT levels, thereby suggesting an increased FVIIa-TF interaction, which may be consistent with increased TF expression/activation due to SARS-CoV2 -induced endotheliopathy.

Enoxaparin in COVID-19 moderate to severe hospitalized patients (INHIXACOV19)

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.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Organizational challenges and oncological activity volumes during the SARS-CoV-2 epidemic peak in Verona, Italy

Background: On February 23rd the first case of SARS-CoV-2 infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22 inpatient beds COVID unit and we had to reshape our organization and personnel to face the SARS-CoV-2 epidemic, while maintaining our oncological activity. Methods: We tracked down oncological activity from January 1st to March 31st, 2020, in relationship to the organizational changes implemented and in comparison to the same period of 2019. We also recorded cases of SARS-CoV-2 infections observed in oncology health professionals and hospital admissions of active oncology patients for SARS-CoV-2 infection. Results: Progressive restrictions in patients', visitors', and caregivers' access to the inpatient and outpatient facilities of the Oncology section and organizational changes were adopted early on during the epidemic peak. Since March 13th, segregated personnel teams were created, one dedicated to the COVID unit and a "clean" one dedicated to oncological patients, resulting in an overall 40% and 43% reduction in oncology-dedicated medical and nursing/auxiliary staff, respectively. As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations, and specialty visits in the period January-March 2020 was 8%, 6%, and 3%, respectively;based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. Patient's acceptance of adopted measures was very high (see abstract by Tregnago D). Overall, 8/85 (9%) health professionals tested positive for SARS-CoV-2 (no hospital admissions and no treatment required) and 7/525 (1.3%) active oncology patients were admitted for SARS-CoV-2 infection (of whom, 2 died of infection-related complications). Conclusions: A minimal (<10%) reduction in Oncology activity was registered during the peak of SARS-CoV-2 epidemic in Verona, Italy. Organizational and protective measures adopted appear to have contributed to keep infections in both health professionals and oncological patients to a minimum. Legal entity responsible for the study: University of Verona. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Management of obstetrics and gynaecological patients with COVID-19

The widespread SARS-CoV-2 implies the application of procedures aimed to detect, isolate, and appropriately manage affected patients in the setting of obstetrics and gynaecologic emergency room and in inpatient setting, such as during labour, delivery, and postpartum. Here we report specific recommendations for the management of suspected and confirmed gynaecologic and obstetrics patients with COVID-19. The checklist developed by the Società Italiana di Malattie Infettive e Tropicali (SIMIT-2, available in English, Italian, Chinese) represents the first step to clas-sify patients who need to be managed following the SIMIT-1 flowchart, applying all the appropriate infection control procedures. In this scenario, the management of pregnant women needs to follow the same procedures as the general population. Nevertheless, as for other potentially severe respiratory infections, pregnant women could be more vulnerable. In this regard, the maternal and foetal interests can be conflicting, such as the choice of the time and mode of delivery or the use of steroids for foetal maturation. More-over, available evidence suggests a maternal-foetal transmission via contact with respiratory secretions and seems to exclude in utero transmission. Therefore, the appropriate management of breastfeeding is unclear, and the temporary separation of the infant from the mother could be an option. Finally, in general, delivery represents a moment of a high risk of infection for healthcare providers, and specific behaviours are mandatory.