Management of Relapsed/Refractory All with Inotuzumab During COVID-19. A Case Report

Management of patients with concomitant acute lymphoblastic leukemia (ALL) and COVID-19 infection is challenging. We describe the clinical history of a 40-year-old male with relapsed B-common ALL who developed Sars-CoV2 prior to treatment initiation with inotuzumab. Since the patient was asymptomatic for COVID-19, the first dose of inotuzumab was administered, followed by remdesivir as prophylaxis. However, a worsening in respiratory findings led to a delay in administering the following doses of inotuzumab. Interestingly, even if the patient did not receive the full inotuzumab cycle, he achieved a complete hematologic remission: furthermore, he spontaneously developed anti-sars-COV2 antibodies. COVID-19 treatment also included convalescent plasma, leading to negativization of the viral load. The patient, after COVID-19 recovery, received a second full cycle of inotuzumab, underwent allogeneic transplantation, and is currently in complete hematologic and molecular remission, in good clinical conditions, five months from allograft

Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study

Coronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load.Objectives: Coronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load. Methods: Adult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidone‑iodine (PVPI) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse. Results: In the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group. Conclusions: Oral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups. Clinical relevance: PVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline

Clinical Characteristics and Outcome of Patients with Suspected COVID-19 in Emergency Department (RESILIENCY Study II)

COVID-19 may show no peculiar signs and symptoms that may differentiate it from other infective or non-infective etiologies; thus, early recognition and prompt management are crucial to improve survival. The aim of this study was to describe clinical, laboratory, and radiological characteristics and outcomes of hospitalized COVID-19 patients compared to those with other infective or non-infective etiologies. We performed a prospective study from March 2020 to February 2021. All patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited. All patients were evaluated according to a predefined protocol for diagnosis of suspected SARS-CoV-2 infection. The primary endpoint was evaluation of clinical, laboratory, and radiological characteristics associated or not with COVID-19 etiology at time of hospitalization in an emergency department. A total of 1036 patients were included in the study: 717 (69%) patients with confirmed COVID-19 and 319 (31%) without COVID-19, hospitalized for other causes. The main causes of hospitalization among non-COVID-19 patients were acute heart failure (44%) and bacterial pneumonia (45.8%). Overall, 30-day mortality was 9% among the COVID-19 group and 35% in the non-COVID-19 group. Multivariate analysis showed variables (fever > 3 days, dry cough, acute dyspnea, lymphocytes 250 ng/mL) independently associated with COVID-19 etiology. A decision tree was elaborated to early detect COVID-19 patients in the emergency department. Finally, Kaplan-Meier curves on 30-day survival in COVID-19 patients during the first wave (March-May 2020, n = 289 patients) and the second wave (October-February 2021, n = 428 patients) showed differences between the two study periods (p = 0.021). Patients with confirmed diagnosis of COVID-19 may show peculiar characteristics at time of hospitalization that could help physicians to distinguish from other infective or non-infective etiologies. Finally, a different 30-day mortality rate was observed during different periods of the pandemic

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Impact of Anti-Endothelial Cell Antibodies (AECAs) in Patients with Polycythemia Vera and Thrombosis

Polycythemia vera (PV) causes thrombosis. Erythrocytosis and cell adhesiveness are responsible for thrombosis. JAK2V617F causes inflammation and autoimmunity; however, whether or not autoimmunity or inflammation causes thrombosis has yet to be proven. In 60 PV patients, we analyzed JAK2V671F and its allele burden, autoimmune Th17 cells, interleukin-17 (IL-17), anti-endothelial cell antibodies (AECAs), endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor antigen (VWF: Ag). Fifty blood donors were used as the controls. All patients were on phlebotomy-maintaining hematocrit <45% and aspirin. Of the 60 patients, 40 had thrombosis. Those patients with thrombosis had a higher JAK2V617F allele burden than those without thrombosis, andTh17 cells and IL-17 were also higher in patients with thrombosis. Interestingly, we observed a high AECA IgG ELISA ratio (ER) in patients with thrombosis, which was normal in patients without thrombosis. We found high ELAM-1 and ICAM-1 as well as high VWF:Ag in patients with thrombosis compared to patients without thrombosis. AECA-positive sera from patients with thrombosis showed enhanced binding to cytokine-treated HUVEC and a positive antibody-dependent cellular cytotoxicity, suggesting that AECA may contribute to vascular injury. A positive correlation between AECAs, allele burden, and thrombosis was found. These results suggest that autoimmunity may be an additional mechanism in PV thrombogenesis

Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests

COVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1α (IL-1α) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), β-Thromboglobulin (β-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1α and IL-8, and TFPI were higher as well as TAT and β-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs

Efficacy of Remdesivir-Containing Therapy in Hospitalized COVID-19 Patients: A Prospective Clinical Experience

Objectives: Remdesivir is currently approved for the treatment of COVID-19. The recommendation for using remdesivir in patients with COVID-19 was based on the in vitro and in vivo activity of this drug against SARS-CoV-2. Methods: This was a prospective observational study conducted on a population of patients hospitalized for COVID-19. The primary endpoint of this study was the impact of remdesivir-containing therapy on 30-day mortality; the secondary endpoint was the impact of remdesivir-containing therapy on the need for high-flow oxygen therapy (HFNC), non-invasive ventilation (NIV), or mechanical ventilation. The data were analyzed after propensity score matching. Results: A total of 407 patients with SARS-CoV-2 pneumonia were consecutively enrolled. Out of these, 294 (72.2%) were treated with remdesivir and 113 (27.8%) were not. Overall, 61 patients (14.9%) were treated during hospitalization with HFNC, NIV, or mechanical ventilation, while 30-day mortality was observed in 21 patients (5.2%). Univariate analysis of patients treated with remdesivir or not showed no differences in 30-day mortality (4% vs. 6%, p = 0.411) in the two study groups. Cox regression analysis, after propensity score matching, showed that therapies, including remdesivir-containing therapy, were not statistically associated with 30-day survival or mortality. The Kaplan–Meier curves of 30-day survival in patients treated with remdesivir or not before (p = 0.24) and after (p = 0.88) propensity score matching showed no differences between the two study groups. Finally, patients treated with remdesivir or not showed the same need for HFNC/NIV or mechanical ventilation. Conclusions: This real-life experience of remdesivir use in hospitalized patients with COVID-19 was not associated with significant increases in rates of survival or reduced use of HFNC/NIV or mechanical ventilation compared with patients treated with other therapies not including remdesivir

Health-related quality of life in survivors of severe covid-19 infection

Background Long-term effects of Coronavirus Disease 2019 (COVID-19) are increasingly recognized as having a significant impact on Health-Related Quality of Life (HRQoL). Understanding HRQoL status for each patient affected by long COVID-19 and its determinants may have a key role to prevent and treat this condition.Methods In this prospective observational study conducted in a large academic COVID-19 hospital in Rome, participants were contacted 2 years after hospital admission for severe COVID-19. To assess HRQoL, EQ-5D-5L and Visual analog scale (EQ VAS) standard questionnaires were administered by interview. Logistic regression model was used to the five health dimensions as dependent variables (0 = no problem, 1 = some/extreme problem).Key results In 137 enrolled patients, the mean pre-COVID and post-COVID EQ-5D-5L index and EQ-VAS score were 0.97 (SD 0.06), 0.79 (SD 0.26) and 72.38 (SD 15.18), respectively. After subdivision of the participants for clinical and social variables, the EQ-5D-5L index resulted significantly lower than in the pre-COVID-19 period. Female gender, unemployed status, and chronic comorbidities were the most common predictors for having any problems in each EQ-5D-5L domain, while also older age and higher Body Mass Index (BMI) showed to be related to a lower EQ-VAS score.Conclusion HRQoL showed to be still low in patients 2 years after acute severe COVID-19. Given the significant impact of SARS-CoV-2 on long-term chronic symptoms, predictors of poor outcomes must be considered during the acute phase of illness to plan a tailored follow-up path for each patient

Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55

Immune Reconstitution and Safe Metabolic Profile after the Switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate among Virologically Controlled PLWH: A 96 Week Update from the BICTEL Cohort

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built. Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4+ T cell count and in CD4+/CD8+ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up. Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55