The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults.

BACKGROUND: Our aim was to investigate the impact of therapeutics with antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mortality of older adults affected by coronavirus disease 2019 (COVID-19), taking into consideration the time interval from symptoms onset to drugs administration. METHODS: Data from 143 COVID-19 patients over 65 years of age admitted to the Humanitas Clinical and Research Center Emergency Department (Milan, Italy) and treated with Lopinavir/ritonavir (LPV/r) or Darunavir/cobicistat (DVR/c) associated to Hydroxychloroquine (HCQ) were retrospectively analyzed. Statistical analysis was performed by using a logistic regression model and survival analysis to assess the role of different predictors of in-hospital mortality, including an early (<6 days from symptoms onset) vs. late treatment onset, signs and symptoms at COVID-19 presentation, type of antiviral treatment (LPV/r or DVR/c) and patients' age (65-80 vs. >80 years old). RESULTS: Multivariate analysis showed that an older age (OR: 2.54) and dyspnea as presenting symptom (OR: 2.01) were associated with higher mortality rate, whereas cough as presenting symptom (OR: 0.53) and a timely drug administration (OR: 0.44) were associated with lower mortality. Survival analysis demonstrated that the timing of drug administration had an impact on mortality in 65-80 years-old patients (p = 0.02), whereas no difference was seen in those >80 years-old. This impact was more evident in patients with dyspnea as primary symptom of COVID-19, in whom mortality decreased from 57.1% to 38.3% due to timely drug administration (OR: 0.5; p = 0.04). CONCLUSIONS: There was a significant association between the use of a combined antiviral regimen and HCQ and lower mortality, when timely-administered, in COVID-19 patients aged 65-80 years. Our findings support timely treatment onset as a key component in the treatment of COVID-19.

The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy.

BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. METHODS: We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. RESULTS: Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60-70, 70-80 and >80 years vs <60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1-3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21-0.62; p < 0.0001). CONCLUSIONS: This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality.

Effectiveness of Streptococcus Pneumoniae Urinary Antigen Testing in Decreasing Mortality of COVID-19 Co-Infected Patients: A Clinical Investigation.

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.

Peripheral Blood Stem Cells versus Bone Marrow for T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Hodgkin Lymphoma.

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P = .405) and platelet (26 versus 26.5 days, P = .994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P = .761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR], .29; P = .006), PFS (HR, .38; P = .001), and GRFS (HR, .44; P = .020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant-specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor.

Methadone in the treatment of pain and terminal delirum in advanced cancer patients.

OBJECTIVE: This prospective study documents the use of methadone as part of an opioid rotation strategy in patients with uncontrolled pain and severe delirium admitted for terminal care to a tertiary cancer palliative care hospital. METHODS: We reviewed the treatment of 20 patients with severe pain and delirium at the end of life who's delirium did not improve 24 h or longer after starting a neuroleptic medication. RESULTS: Ten male and 10 female patients, 47 to 77 years old, were rotated or "switched" to methadone due to uncontrolled pain in the setting of delirium, limiting further opioid dose escalation. At 2 weeks, a total of 10 patients had expired. Of the 10 patients who were alive 2 weeks after starting methadone, 7 patients were stable on an average of 1.1 mg/h methadone, 2 patients were restarted on morphine IV and one on Percocet. The calculated average equianalgesic dose of methadone was 9% (2%-17%) of the previous morphine-equivalent dose. Of the 20 patients who were switched to methadone for what appeared to be terminal delirium, the pain control was significant in 15, moderate in 3, and unchanged in 2 patients. Average analgesia was good to excellent (average Numeric Analog Scale rating [NAS] decreased from 8.2 to 2.5). Sedation had decreased from 1.65 to 0.55 on a scale of 0 to 3. Of the 20 patients, improvement of cognitive status was significant in 9, moderate in 6, partial in 2, and none in 3 patients. The Memorial Delirium Assessment Scale (MDAS) showed improvement from an average of 23.6 prior to the switch to 10.6 3 days after. Decreased alertness on methadone was devoid of agitated features. SIGNIFICANCE OF RESULTS: Our study suggests that methadone can be effective in the treatment of both refractory pain and what appears to be terminal delirium. Most patients in our group had at least a short-term improvement in mental status as well as significant and lasting improvement in analgesia.