Antiandrogen agents in COVID-19: a meta-analysis of randomized trials.

INTRODUCTION: Antiandrogen therapy can reduce the expression of transmembrane protease 2, which is essential for severe acute respiratory syndrome coronavirus-2 to enter the host cells. Prior trials suggested the efficacy of antiandrogen agents in patients with COVID-19. We investigated whether antiandrogen agents reduce mortality compared to placebo or usual care. EVIDENCE ACQUISITION: We searched for randomized controlled trials comparing antiandrogen agents with placebo or usual care alone in adults with COVID-19 in PubMed, EMBASE, the Cochrane Library, the reference lists of retrieved articles, and publications by manufacturers of antiandrogen agents. The primary outcome was mortality at the longest follow-up available. The secondary outcomes included clinical worsening, the need for invasive mechanical ventilation, admission to the intensive care unit, hospitalization, and thrombotic events. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022338099). EVIDENCE SYNTHESIS: We included 13 randomized controlled trials enrolling 1934 COVID-19 patients. We found that antiandrogen agents reduced mortality at the longest follow-up available (91/1021 [8.9%] vs. 245/913 [27%]; risk ratio =0.40; 95% confidence interval, 0.25-0.65; P=0.0002; I2=54%). Antiandrogen therapy also reduced clinical worsening (127/1016 [13%] vs. 298/911 [33%]; risk ratio =0.44; 95% confidence interval, 0.27-0.71; P=0.0007; I2=70%) and hospitalization (97/160 [4.4%] vs. 24/165 [15%]; risk ratio =0.24; 95% confidence interval, 0.10-0.58; P=0.002; I2=44%). There was no significant difference in the other outcomes between the two treatment groups. CONCLUSIONS: Antiandrogen therapy reduced mortality and clinical worsening in adult patients with COVID-19.

Reducing mortality in acute kidney injury patients: systematic review and international web-based survey.

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.

Feasibility, safety and efficacy of COVID-19 severe acute respiratory distress syndrome management without invasive mechanical ventilation.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible. METHODS: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS). RESULTS: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality. CONCLUSIONS: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

A novel evidence-based algorithm to predict thromboembolism in patients with COVID-19: preliminary data from a single-center cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19. METHODS: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results. RESULTS: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed. CONCLUSIONS: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.