One year health-related quality of life after discharge: a prospective cohort study among COVID-19 ICU survivors

Considering the paucity of data on long-term Health-Related Quality of Life (HRQoL) in coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors, we present one-year follow-up results on patients' HRQoL and compare them with those of the already reported 6-month follow-up. We conducted a prospective cohort study of patients in COVID-19 ICU between March and June 2020. A HRQoL analysis was performed six months and 1 year after discharge by means of a short-form-36 (SF-36) questionnaire. Hospital mortality in 403 ICU COVID-19 patients was 44.9%;further 4.0% died between hospital discharge and 6-month follow-up and only 0.5% died in the next six months. The median physical component of HRQoL increased from 43.7 (interquartile range (IQR): 31.7-52.7) at 6 months to 46.0 (IQR: 38.0-53.0) 1 year after hospital discharge (p = 0.007). In multivariable regression analysis, age >50 (odds ratio (OR) 0.270) and female sex (OR 0.144) were independently associated with reduced physical HRQoL 1 year after discharge. The median mental component of HRQoL increased from 50.6 (IQR: 42.0-55.8) at 6 months to 53.0 (IQR: 47.0-56.0) 1 year after discharge (p = 0.035), with no significant predictors. Increased HRQoL was associated with an improvement in patients' physical status, role functioning, emotional well-being (all p < 0.001) and social functioning (p = 0.007). ICU COVID-19 patients' HRQoL slightly improved 1 year after discharge, when compared to results of the 6-month follow-up. Medications received during ICU stay had no effect on physical or mental HRQoL.Copyright © 2023 The Author(s). Published by MRE Press.

A phase 3 study to evaluate the efficacy and safety of reparixin in severe COVID-19 pneumonia

Introduction: The clinical progression of severe coronavirus disease 2019 (COVID-19) is associated with uncontrolled activation of inflammatory cytokines that results in excessive tissue injury, among which is interleukin-8 (IL-8). Aim(s): To assess the efficacy and safety of reparixin, an inhibitor of IL-8 receptors, as add-on therapy to the standard of care for severe COVID-19 pneumonia. Method(s): This was a Phase 3, multicenter, randomized, placebo-controlled study in hospitalized adult patients with COVID-19 requiring oxygen support and/or noninvasive ventilation. From February to July 2021, patients were randomized 2:1 to oral reparixin or placebo in addition to the standard of care for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure. This study was funded by Dompe Farmaceutici SpA (ClinicalTrials.gov: NCT04878055). Result(s): Of the 278 randomized patients, 185 patients in the reparixin group and 94 patients in the placebo group were included in the primary intention-to-treat analysis. The proportion of patients alive and free of respiratory failure at day 28 was greater in the reparixin group but not statistically significant (n=152 (89.4%) vs. n=71 (85.5%), OR: 1.63, 95% CI: 0.75 - 3.51, p= 0.2). While time to recovery was not different between groups, patients who received reparixin had a lower intensive care unit admission rate. Reparixin was well-tolerated. Conclusion(s): This trial did not meet the primary efficacy endpoint due to the low mortality in both arms, yet reparixin showed a promising trend towards limiting disease progression. A confirmatory Phase 3 study is currently underway.

Sex differences in hospitalized COVID-19 patients

The novel coronavirus disease (COVID-19) affected females less than males, as demonstrated by sex-disaggregated data present in the literature. During the first wave, females hospitalized at San Raffaele Hospital, Milan, Italy were few in number, presented symptoms later and had less critical clinical conditions than males. The present study aimed to evaluate the epidemiological status of the female population during the second wave, which occurred in Autumn 2020 in Italy. This prospective cohort study included all patients, with a positive real-time reverse-transcriptase polymerase chain reaction for COVID-19, who attended the emergency department or were hospitalized in wards and/or intensive care unit (ICU) from 29th September 2020 to 29th November 2020. A total of 1216 COVID-19 patients were included, of whom 459 (37.8%) were females. The percentage of females admitted was 41.3% in the first period and 36.3% in the second period, without significant increase over time (p = 0.3). Females accounted for 25% of all COVID-19 intensive care unit admissions. There was significantly sex-based difference in the overall hospital mortality (4.1% for females and 11.3% for males, p < 0.0001). At San Raffaele Hospital, Milan, Italy during the second wave, female patients were few and affected by a less severe form of COVID-19. An increase over time of females hospitalized patients was not reported, unlike what was previously demonstrated during the first wave. Copyright © 2022 The Author(s). Published by MRE Press.

A Phase 2 Multicenter, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Reparixin in Hospitalized Adult Patients with COVID-19 Pneumonia

Rationale: Severe coronavirus disease 2019 (COVID-19) is associated with significant morbidity attributed from the complications of acute respiratory distress syndrome. Poor outcomes in severe COVID-19 patients have been related to cytokine release syndrome, which may be mediated by CX- C chemokine ligand 8/interleukin 8 (CXCL8/IL-8) acting through C-X-C chemokine receptor types 1 and 2 (CXCR1/2). The aim of this clinical trial was to determine if CXCR 1/2 blockade by reparixin, an IL-8 inhibitor, can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. Methods: This was a Phase 2, open-label, adaptive, multicenter, randomized trial in hospitalized adult patients, conducted in Italy and Brazil, with severe COVID-19 pneumonia between May and November 2020. Eligible patients had respiratory distress (respiratory rate ≥30 breaths/minute without oxygen and/or partial arterial oxygen pressure (PaO2)/fraction of inspiration O2 (FiO2) >100 to <300 mmHg), pneumonia confirmed by chest imaging, and elevated inflammatory markers. Patients were randomized 2:1 to receive oral reparixin 1200mg three times daily or the standard of care (SOC) for up to 21 days. Patients were followed for up to seven days after the end of treatment. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensivecare unit admission, and/or use of rescue medication. This study was funded by Dompé Farmaceutici SpA (ClinicalTrials.gov: NCT04794803). Results: Fifty-five patients were enrolled and included in the final analysis comparing reparixin (n = 36) to the SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared to the SOC group (16.7% [95% CI: 6.4-32.8%] vs 42.1% [95% CI: 20.3-66.5%], p=0.02). After controlling for covariates, this statistical significance was maintained with a hazard ratio of 0.33 (95% CI, 0.11 to 0.99;p = 0.047). Reparixin treatment appeared to be well-tolerated with no discontinuation of therapy. Conclusions: In patients with severe COVID-19, reparixin led to a significant improvement in clinical outcomes when compared to the SOC. The results of this phase 2 study allowed progression to a Phase 3 clinical trial to further explore the efficacy and safety of reparixin for the treatment of severe COVID- 19.

Inverse correlation between central hypogonadism and circulating IL-10 levels in males with severe COVID-19

Introduction & Objectives: After the early and dramatic induction of inflammatory cytokines, IL-6 emerged to be associated with severe outcomes in patients with COVID-19. Likewise, high IL-10 plasma levels have been reported, and central hypogonadism has been recently observed in male patients with severe clinical outcomes (i.e., Intensive Care Unit (ICU) admission or death) of COVID-19. We aimed to investigate the role of IL-10 over the pathophysiology of COVID-19 and its relationship with hypogonadism in males. Materials & Methods: Plasma from 281 voluntary healthy males (HC) and 258 laboratory-confirmed COVID-19 males (i.e., asymptomatic (n=24);symptomatic (n=155);ICU patients (n=48);and, deceased (n=31)) was collected to measure levels of total testosterone (TT), IL-10 and the nonclassical MHC class I HLA-G (HLA-G) molecule - associated to IL-10 and involved in immune escape after viral infection - by specific enzyme-linked immunosorbent assay. Results: An inverse correlation between TT and IL-10 levels was identified, with TT levels progressively decreasing from HC (median (IQR) 10.4 (8.1-13.4) nmol/L) to asymptomatic COVID-19 (3.9 (3.1-5.3) nmol/L), to symptomatic COVID-19 (3.0 (1.8-5.7) nmol/L), ICU (1.0 (0.5-1.8) nml/L) and deceased (0.7 (0.3-2.3) nmol/L) patients, respectively (p<0.0001). Conversely, IL-10 levels progressively decreased from deceased COVID-19 patients (11.3 (4.5-37.7) pg/ml), to ICU (8.0 (2.6-16.7) pg/mL), symptomatic (6.0 (3.0-10.9) pg/mL), asymptomatic COVID-19 patients (6.0 (1.6-6.0) pg/mL), and HC (3.0 (1.3-3.0) pg/mL), respectively (p<0.0001). Similarly, HLA-G levels, progressively increased from HC to COVID-19 patients with most severe clinical outcomes. Conclusions: These data indicate that circulating TT is inversely associated to both IL-10 and HLA-G levels in men with COVID-19, where lower TT and higher IL-10 levels are associated with the most severe clinical outcomes. Further investigations are required to better define whether TT and IL-10 might be early effective biomarkers of clinical severity in males with COVID-19 and to exploit if TT is involved in promoting IL-10 and HLA-G induction.

Severely low testosterone in men with COVID-19: A case-control study

Introduction & Objectives: In patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) reasons for sex disparity in disease severity are still unclear and circulating androgens could play a role. We investigated circulating sex steroids levels in a cohort of symptomatic patients with COVID-19 compared to a cohort of healthy men. Materials & Methods: Data of 286 patients with COVID-19 admitted to a single academic centre were compared to 305 voluntaryhealthy blood donors. Patients were further categorized according to disease severity as: Group 1: mildly symptomatic and discharge home;Group 2: admitted in the internal medicine unit;Group 3: admitted to intensive care unit (ICU);and, Group 4: deceased because of COVID-19. Healthy controls were subdivided in SARS-CoV-2 negative and asymptomatic unaware SARS-CoV-2 positive. Health-related comorbidities were scored with the Charlson Comorbidity Index (CCI). Moreover, a validated composite risk score (Liang et al, 2020) was calculated to estimate the risk of developing critical illness in men with COVID-19. Hypogonadism was defined as a total testosterone (TT) level < 9.2 nmol/l. Logistic regression analysis tested the association between TT level and the risk of death due to COVID-19. Results: Overall, men with COVID-19 showed a higher burden of comorbidities than healthy controls and asymptomatic positive controls (CCI³2 in 66/286 (24%) vs. 0/281 (0%) vs. 0/24 (0%);p<0.0001). TT levels were significantly lower in patients with COVID-19 vs. asymptomatic vs. healthy controls (mean (IQR) 2.5 (1-4.7) nmol/L) vs. 11.8 (8.4-14.4) vs. 10.4 (8.1-13.4) nmol/L, respectively;p<0.0001). Of all, hypogonadism was observed in 257 (89.8%) patients, 9 (33%) asymptomatic and 42 (14.9%) healthy controls at hospital admission (p<0.0001). In as many as 243 (85%) patients, hypogonadism was secondary. Of patients, in Group 1 were 24 (4.5%), in Group 2: 155 (29%), in Group 3: 48 (8.9%), and in Group 4: 31 (5.8%). Both Group 3 and 4 patients had significantly lower TT (1.0 (0.5,1.8) and 0.7 (0.3,2.3) nmol/L, respectively) compared to Group 2 (3.0 (1.8,5.7)) and Group 1 (3.9 (3.1,5.3) nmol/L) patients (p<0.0001). At logistic regression, a lower TT level was associated with a higher risk of death (OR: 0.66;95%CI 0.45, 0.98) after accounting for the critical illness score. Of note, the lower the TT, the higher the risk of death for the same Critical-Ill COVID-19 score (Figure 1).(Figure Presented) Conclusions: We unveiled an independent association between SARS-CoV-2 infection status and hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

Awake pronation with helmet continuous positive airway pressure for COVID-19 acute respiratory distress syndrome patients outside the ICU: A case series.

OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.

Use of Defibrotide in Patients with COVID-19 Pneumonia;Results of the Defi-VID19 Phase 2 Trial

Background: The clinical spectrum of COVID-19 ranges from pauci-symptomatic forms to severe disease characterized by respiratory failure requiring mechanical ventilation and intensive care unit (ICU) management, as well as multisystem involvement characterized by sepsis, organ dysfunction and death. Treatment of COVID-19 is not standardized, and respiratory failure from ARDS is the leading cause of mortality;in-hospital mortality at 28-days in our tertiary care center in Lombardia, northern Italy was 23% during the first wave in 2020(Ciceri et al. 2020). Endothelial damage and thrombo-inflammation have been identified as common to both COVID-19 pathophysiology and veno-occlusive disease (VOD/SOS). Defibrotide (DF) has endothelial-protective properties, with pro-fibrinolytic, anti-thrombotic, anti-ischemic, anti-inflammatory, and anti-adhesive activity, but no significant systemic anticoagulant effects and is approved for the treatment of severe VOD/SOS. Aim: A prospective, multicenter, phase II, single-arm, open label trial (DEFI-VID19, NCT04335201) was conducted in patients (pts) with COVID-19 ARDS to evaluate the efficacy of DF in addition to best available therapy per institutional guidelines. The primary endpoint was respiratory-failure rate (RFR) defined as progression of respiratory failure, i.e. severe gas transfer deficit (PaO2/FiO2<200 mmHg), need of ICU or death at day+14 from treatment start. Secondary endpoints included overall survival (OS) at 28 days, duration of hospitalization and safety. A sample size of 50 pts was calculated to detect an absolute reduction of 20% in RFR at day+14, assuming a failure rate in non-treated pts of 70% (alpha=5%, power=90%, two-sided test). Pts received DF intravenously at 6.25 mg/kg/dose by 2-hour infusion repeated every 6 hours. Expected treatment duration was 14 days, with earlier discontinuation if clinical improvement occurred. LMWH at prophylactic dose was allowed. Approval was provided by the National IRB for COVID-19 trials at Institute Spallanzani (Rome) and by the Italian Agency for Drug (AIFA). All patients provided written informed consent. Results: Overall, 52 pts were enrolled from September 2020 to April 2021;48 were evaluated for efficacy and safety;4 pts were excluded due to screen failure (n=2) or withdrawal of informed consent at day 2 after defibrotide was initiated (n=2). Median age was 60.5 years (range 53-71);35 pts (73%) were male and 65% had comorbidities, with high blood pressure, obesity and COPD most common. Two pts had pre-existing diagnoses of non-Hodgkin lymphoma. Median time from onset of COVID-19 symptoms and from Sars-COV2 PCR by nasal swab to enrollment were 8 (range 7-10) and 3 days (range 1-6), respectively. All pts were hospitalized and scale 5 of 8-category ordinal scale by WHO criteria, requiring noninvasive ventilation with CPAP or high-flow oxygen, with a median P/F ratio of 211 (range 134-275) mmHg. At treatment start, the median and (range) lymphocyte counts, LDH, CRP, ferritin, D-dimer and IL-6 were 0.7 (0.5-0.9) x 10e9/L;404 (291-491) U/L;49 (22-97) mg/L;823 (363-1088) ng/ml;0.44 (0.28-1.29) µg/mL and 20 (11-32), respectively. Median treatment duration was 8.5 days (range 6-11). Overall, 13/48 pts (27%) discontinued the treatment due to clinical worsening and/or need of further therapies: 9 pts experienced progressive respiratory failure and 6 of those were transferred to ICU for IOT (one pt required ECMO), and 4 required full anticoagulation due to pulmonary embolism (n=1), ischemic stroke (n=1), and femoral deep venous thrombosis (n=2). All pts who completed the treatment 35/48 (73%) were discharged with no need of oxygen support. Overall, 14 SAEs have been reported in a median time of 6 days (range 2-10): all unrelated to DF. No pts experienced hemorrhagic events. The incidence of RFR at day 14 was 25 (+/- 6)%, and at day 28, 27 (+/- 6) %. Probability of OS at day 28 was 89 (+/-4) %, at day 60 83 (+/- 5)%. Overall, 8 pts died from COVID-19 -related complications. No pts required re-admission after hospital discha ge (median 14 days) or died after discharge. Conclusion: Treatment with DF in pts with grade 5 WHO COVID 19 ARDS does not induce bleeding, and is associated with rapid restoration of respiratory function (73% of pts). Notably, no oxygen support was needed at discharge and a 1-month OS rate of 89% was observed, which is higher than historical controls (77%) treated in the same setting. Disclosures: Richardson: Takeda: Consultancy, Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy, Research Funding;AstraZeneca: Consultancy;Oncopeptides: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding;Protocol Intelligence: Consultancy;Secura Bio: Consultancy;Regeneron: Consultancy;Celgene/BMS: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Janssen: Consultancy;Sanofi: Consultancy. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Carlo-Stella: Incyte: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi: Consultancy, Research Funding;AstraZeneca: Honoraria;Celgene: Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Oncology: Honoraria;Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Mechanical ventilation. Total eclipse of the heart (editorial)

Results from recent large randomized trials investigating the use of high PEEP in patients without ARDS all suggest that high levels may increase mortality due to hypotension and bradycardia. A careful assessment of cardiac function — with particular focus on the right ventricle — should be performed before planning our ventilation strategy in any setting, including COVID-19 and ARDS in general. Mechanical ventilation should be respectful in regards of heart function, and tolerant with moderate hypoxia and hypercapnia, noninvasive (whenever possible) and synchronized.

Estimating sars-cov-2 infection fatality rate using data from one of the most affected areas worldwide

The real estimate of the infection fatality rate of SARS-CoV-2 is a pivotal aspect of the COVID-19 pandemic. However, this number is still debated, since both the numerator and the denominator are uncertain. Data analysis from the most affected areas in the world minimizes computational errors and represents a unique approach for estimating infection fatality rate. We first extracted data from PubMed/Medline, Google, traditional media and social media to obtain the rate of SARS-CoV-2 antibodies seroprevalence in the most affected and best-studied areas in the world: Val Seriana (Italy), Ischgl (Austria) and Manaus (Brasil). We then searched mortality data from national institutes of statistics and calculated excess mortality. We estimated the infection fatality rate considering several scenarios according to the mortality attributable to COVID-19 and the proportion of the population infected with the virus. We found that the seropositivity was surprisingly close to 40% in all the considered areas. We calculated the SARS-CoV-2 infection fatality rate for Val Seriana, using from half to the entire excess mortality (1208 deaths) and considering from 40% to 80% of the population as being infected with SARS-CoV-2. In the most conservative scenario, infection fatality rate was as low as 0.55%, while in the worst-case one it was 2.2%. We found that the seroconversion rate in the most affected areas worldwide is about 40%. We consequently estimated the infection fatality rate to be between 0.55% and 2.2% in an area with a relatively elderly population. © 2021 The Author(s). Published by MRE Press.

Angiotensin II infusion and markers of organ function in invasively ventilated COVID-19 patients

Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg;95% CI, 1.87-16.22;P = 0.013) and the PaO2/FiO(2) ratio (median difference, 23.17;95% CI, 3.46-42.88;P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32;95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO2/FiO(2) ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy

Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ;IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mug/m;IQR, 5.0-23.8 mug/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P = 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration: ClinicalTrials.gov identifier: NCT04318366.

Fast reshaping of intensive care unit facilities in a large metropolitan hospital in Milan, Italy: facing the COVID-19 pandemic emergency

At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute - a large tertiary hospital and research centre in Milan, Italy - was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.