Early rehabilitation treatment in hospitalized patients with severe COVID-19: Effects on autonomy and quality of life

PURPOSE: The aim of our study is to evaluate effects of early rehabilitation treatment in hospitalized patients with severe COVID-19, in order to improve patients' autonomy and quality of life. METHODS: This observational study has been performed in hospitalized patients with severe COVID-19. All patients were evaluated at T0 using specific scales: Modified Barthel Index (MBI) for autonomy in ADL, Mini Mental State Examination (MMSE) for cognitive status, Borg scale for dyspnoea, EQ5D scale for quality of life. In absence of contraindications for the rehabilitation treatment, patients start early a rehabilitation protocol consisting of one session (30 minutes) per day, for 2 to 3 weeks;these scales have been repeated at patient's demission (T1). RESULTS: 70 patients (37 women and 33 men, with average age of 71 years) with severe COVID-19 were included in the study. After rehabilitation treatment, MBI increases statistically significantly from T0 to T1 (39.8±35.0 with 95% CI 31.6-48, vs 69.8±38.1 with 95% CI 60.8-78.7, p < 0.001);besides MBI at T0 correlates inversely and statistically significantly with all EQ-5D variables at T0, similarly at T1 (p < 0.001), indicating the improvement of autonomy and therefore of the quality of life. The MMSE correlates statistically significantly with MBI at T0 and T1 (r = 0.569, r = 0.747 respectively, p < 0.001), indicating that an adequate cognitive status is connected with a greater increase in autonomy in ADL after rehabilitation treatment. MBI correlates directly and significantly with the PaO2/FiO2 value both at T0 and T1 (r = 0.263 with p = 0.039, r = 0.389 with p = 0.023 respectively), indicating that improving the oxygen exchanges also improves the patient's autonomy. CONCLUSIONS: An early rehabilitation treatment should promote autonomy and a better quality of life in patients with COVID-19. © 2022-IOS Press. All rights reserved.

A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL

Background: Trans-arterial chemoembolization (TACE) is the gold-standard for intermediate stage HCC. We hypothesised the ischemic and cytotoxic effect of TACE to boost anti-cancer immunity and to synergise with the anti PD-1 pembrolizumab (pembro). We designed a phase Ib study to test the safety and preliminary efficacy of pembro after TACE in intermediate HCC. Methods: PETAL study will enroll up to 32 patients with intermediate HCC to receive pembro 200 mg every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. The first safety-run-in phase includes 6 patients: if no dose limiting toxicities (DLTs) emerge over a 21-day window after first pembro, the others are enrolled in the expansion phase. Pembro is given within 30 days after 1 or 2 TACEs. The first phase includes 1 patient scoring Child-Pugh (CP)-B7 and the remaining have to be CP-A. Safety is the primary endpoint and is measured as the incidence of treatment-related adverse events (TRAEs), graded according to NCI CTCAEv4. Efficacy is the secondary endpoint and is evaluated as progression free survival (PFS) from first TACE, according to mRECIST criteria. Survival is estimated using Kaplan-Meier method. All the patients who have received at least one dose of pembro are evaluable for safety. Results: At the time of data cut-off, on the 14th of January 2022, 14 patients had received at least one dose of pembro. The median age was 72 (IQR: 63.3-74.6), 79% were male, 71% were cirrhotic, 29% had viral hepatis and 43% ECOG PS 1. One patient had Child-Pugh (CP) class B7 and 13 had A. The median number of nodules was 1.5 (IQR:1-2.8), and 4.1 cm (IQR: 3.7-4.5) the median diameter. Overall, 5 patients received 2 TACEs and 9 had 1. Patients received a median of 4.5 cycles (IQR: 2.3-6.5) of pembro. No DLTs emerged in the first phase. Treatment-related adverse events (TRAE) of any grade (G) were reported in 86% of participants, 21% of participants experienced G3 TRAEs, and there were no G4 or G5 TRAEs. Specific skin-related toxicity was the most frequently reported (35%) TRAE. No patients had treatment-related liver toxicity. Causes of treatment discontinuation were PD (n=7), TRAEs (n=1), clinical deterioration in the CP B patient (n=1), COVID pandemic (n=2) and withdrawal of consent (n=1);at the time of data cut-off, mPFS from first TACE was 10.8 months (95%CI: 6.63-14.97). Conclusions: Adjuvant pembro following TACE is manageable and tolerable with signs of activity. These results prompt the investigation in larger trials.

Role of endothelium activation biomarkers in prediction COVID-19 related intra-Hospital Mortality

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.

COVID-2019: Role of the epidemiological criterionin the diagnostic work-up

In April, a 58-year-old woman was admitted to our hospital for dyspnea. She was a healthy nonsmoker. She lived in a place with ahigh burden of Covid disease. The symptoms started in early March,when her husband was found positive for Sars-CoV2 infection andwas transferred to the Covid Hospital. Her asymptomatic daughterwas also found to have a positive nasal swab, whilst the patientturned out to be negative. For the persistence of dyspnea, she arrived to our hospital and isolated in the restricted Covid area, basedon the epidemiological criterion. A second swab performed, whichwas negative. ABG and walking test were within normal limits. Laboratory tests showed normal blood cell counts, PCR, PCT and Ddimer were normal. H1N1 was not detected. ChestX-ray showed alimited area of thickening in the right middle lobe. Dyspnea was stillthe main complaint. Thus, a test for IgM/IgG against Sars-CoV-2was ordered, which revealed the presence of serum specific IgG;CTscan showed widespread reticular thickening of the peripheral interstitium. The patient was transferred to the internal medicine wardand was maintained in isolation. Therapy with azithromycin and hydroxychloroquine was begun;a third nasal swab eventually yieldeda positive result for Sars-CoV2 infection. The patient was finally transferred to the Covid Hospital and discharged home after one month.This case shows that: 1) the epidemiological criterion remains paramount for diagnosis of Covid19 infection;2) the latency period ofthe virus may vary;3) CT scan is a relevant tool in the diagnosticwork-up, particularly in doubtful cases.

COVID-19 or 'cOVID-19-Like'? Still much to learn

Description of the case: In March 2020 an 84-year-old man washospitalized for fever and dyspnea. He had no history of respiratorydisease. Lived in a place where Covid-disease was highly prevalent. He was brought in the restricted Covid area. Mild leukocytosiswith lymphopenia, elevated PCR and D-dimer were observed. Severe hypoxia and low P/F were recorded on ABG. ChestX-rayshowed bilateral areas of parenchymal thickening. The nasal swabwas negative for SARS-CoV-2. Therapy with oxygen, azithromycin,hydroxychloroquine and lopinavir/ritonavir was started. During hospital stay, the patient tested negative for SARS-CoV-2 on two separate occasions. CT showed severe bilateral interstitial diseasewith a centripetal ground glass pattern.He was moved to the medicine ward where he was maintained in isolation. Therapy also included meropenem and heparin. A fourth nasal swab was stillnegative. A repeat CT confirmed amelioration of the interstitial involvement. The patient was discharged home 35 days later withno supplemental oxygen prescription. Conclusions: This case shows the existence of patients fulfillingall epidemiological, clinical, laboratory, and radiological criteriafor COVID-disease, despite persistently negative nasal swabs.Moreover, the so-called COVID treatment led to improvement ofdisease and discharge from hospital in the patient depicted here.Is it therefore a COVID-19-like or 'true' COVID-19 disease, wherethe clinical manifestations were possibly due only to a hyper-immune stimulation, with the virus meanwhile being no longer detectable? Further studies are thus needed to clarify these issuesin this subgroup of COVID-like patients.