Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure.

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients' memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients' memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients' experience during the day spent before ICU admission may be associated with psychological sequelae.

Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study.

PURPOSE: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors. MATERIAL AND METHODS: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index. RESULTS: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018). CONCLUSIONS: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months.

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

Excessive Sedation as a Risk Factor for Delirium: A Comparison between Two Cohorts of ARDS Critically Ill Patients with and without COVID-19.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation­in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality­between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16−27) vs. 14 (10.5−19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Neurologic and cognitive sequelae after SARS-CoV2 infection: Different impairment for ICU patients.

The exact incidence of neurological and cognitive sequelae of COVID-19 in the long term is yet unknown. The aim of this research is to investigate the type of neurological and cognitive impairment in COVID-19 cases of different severity. Two hundred fifteen patients, who had developed COVID-19, were examined 4 months after the diagnosis by means of neurological exam and extensive cognitive evaluation, investigating general cognition, memory, verbal fluency, visuospatial abilities and executive functions. Fifty-two of them were treated in intensive care unit (ICU patients), whereas 163 were not hospitalized (non-ICU patients). Neurological deficits were found in 2/163 (1.2%) of non-ICU and in 7/52 (13.5%) of the ICU cases, all involving the peripheral nervous system. ICU patients performed significantly worse in all the neuropsychological tests and showed a worse age- and education-corrected cognitive impairment: Cognitive Impairment Index (CII) was higher in ICU than in non-ICU patients (median ICU 3 vs 2, p = .001). CII significantly correlated with age in both groups, was unrelated to length of follow- up, diabetes and hypertension and - only for ICU patients- to PaO2/FiO2 at ICU admission. Obtained results support the greater susceptibility of COVID-19 patients, treated in ICU, to develop neurological deficits and cognitive impairment at a four-month follow up, as compared to cases with mild/moderate symptoms.

Long-term complications of COVID-19 in ICU survivors: what do we know?

Coronavirus disease 2019 (COVID-19) has caused more than 175 million persons infected and 3.8 million deaths so far and is having a devastating impact on both low and high-income countries, in particular on hospitals and Intensive Care Units (ICU). The ICU mortality during the first pandemic wave ranged from 40% to 85% during the busiest ICU period for admissions around the peak of the surge, and those surviving are frequently faced with impairments affecting physical, cognitive, and mental health status, complicating the postacute phase of COVID-19, which in the pre-COVID period, were defined collectively as postintensive care syndrome (PICS). Long COVID is defined as four weeks of persisting symptoms after the acute illness, and post-COVID syndrome and chronic COVID-19 are the proposed terms to describe continued symptomatology for more than 12 weeks. Overall, 50% of ICU survivors suffer from new physical, mental, and/or cognitive problems at 1 year after ICU discharge. The prevalence, severity, and duration of the various impairments in ICU survivors are poorly defined, with substantial variations among published series, and may reflect differences in the timing of assessment, the outcome measured, the instruments utilized, and thresholds adopted to establish the diagnosis, the qualification of personnel delivering the tests, the resource availability as well diversity in patients' case-mix. Future longitudinal studies of adequate sample size with repeated assessments of validated outcomes and comparison with non-COVID-19 ICU patients are needed to fully explore the long-term outcome of ICU patients with COVID-19. In this article, we focus on chronic COVID-19 in ICU survivors and present state-of-the-art data regarding long-term complications related to critical illness and the treatments and organ support received.

Physical, cognitive and mental health outcomes in 1-year survivors of COVID-19-associated ARDS.

We report on the outcome of 114 COVID-19-associated acute respiratory distress syndrome (ARDS) survivors evaluated at 3, 6 and 12 months after intensive care unit discharge with assessment of physical, mental and cognitive impairments. Critical illness polyneuromyopathy was diagnosed in 23 patients (39%). Handgrip dynamometry was 70% predicted at 3 months and significantly improved over time, whereas the 6 min walk test (80% predicted) and severe fatigue (27% of patients) did not. Independence in activities of daily living (ADL) was achieved by 98% at 3 months. Cognitive impairment (28% at 3 months) improved over time, whereas depression, anxiety and post-traumatic stress disorder symptoms, present in 9%, 10% and 4% at 3 months, did not. Normalised health-related quality of life was good. COVID-19-associated ARDS leads to persisting impairment in performance-based measures of physical function, while ADL, cognitive and mental health status, and health-related quality of life may be less impaired. Trial registration number NCT04608994.

C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age.

A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04-5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.

Epidemiological and Clinical Characterization of Superinfections in Critically Ill Coronavirus Disease 2019 Patients.

To describe the epidemiology of superinfections (occurring > 48 hr after hospital admission) and their impact on the ICU and 28-day mortality in patients with coronavirus disease 2019 with acute respiratory distress syndrome, requiring mechanical ventilation. DESIGN: Retrospective analysis of prospectively collected observational data. SETTING: University-affiliated adult ICU. PATIENTS: Ninety-two coronavirus disease 2019 patients admitted to the ICU from February 21, 2020, to May 6, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of superinfection at ICU admission was 21.7%, and 53 patients (57.6%) had at least one superinfection during ICU stay, with a total of 75 (82%) ventilator-associated pneumonia and 57 (62%) systemic infections. The most common pathogens responsible for ventilator-associated pneumonia were Pseudomonas aeruginosa (n = 26, 34.7%) and Stenotrophomonas maltophilia (n = 14, 18.7%). Bloodstream infection occurred in 16 cases, including methicillin-resistant Staphylococcus epidermidis (n = 8, 14.0%), Enterococcus species (n = 6, 10.5%), and Streptococcus species (n = 2, 3.5%). Fungal infections occurred in 41 cases, including 36 probable (30 by Candida albicans, six by C. nonalbicans) and five proven invasive candidiasis (three C. albicans, two C. nonalbicans). Presence of bacterial infections (odds ratio, 10.53; 95% CI, 2.31-63.42; p = 0.005), age (odds ratio, 1.17; 95% CI, 1.07-1.31; p = 0.001), and the highest Sequential Organ Failure Assessment score (odds ratio, 1.27; 95% CI, 1.06-1.63; p = 0.032) were independently associated with ICU or 28-day mortality. CONCLUSIONS: Prevalence of superinfections in coronavirus disease 2019 patients requiring mechanical ventilation was high in this series, and bacterial superinfections were independently associated with ICU or 28-day mortality (whichever comes first).

BMI and pneumonia outcomes in critically ill covid-19 patients: An international multicenter study.

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

Use of critical care resources during the first 2 weeks (February 24-March 8, 2020) of the Covid-19 outbreak in Italy.

BACKGROUND: A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. RESULTS: In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24-March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. CONCLUSIONS: Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.

Laboratory considerations amidst the coronavirus disease 2019 outbreak: the Spedali Civili in Brescia experience.

Coronavirus disease 2019 emergency has created an enormous stress on providers that have been transformed into coronavirus disease hospitals. This article presents the experience of the clinical laboratory of Spedali Civili in Brescia (a teaching hospital in Lombardy with over 1500 beds) in managing the crisis, and to offer practical considerations for laboratory testing for this cohort of patients. Our contribution is threefold: by comparing the demand for tests in two representative period before and within the crisis, we show the change in compositions of the analytes that other labs may expect; we present the new panels of tests that hospital staff can order with different advantage for wards and laboratory; and we show how to reorganize staff on the basis of changes mentioned above.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Management of Patients on Dialysis and With Kidney Transplantation During the SARS-CoV-2 (COVID-19) Pandemic in Brescia, Italy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7-10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management.

Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brescia, Italy.

PURPOSE: An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving. MATERIALS AND METHODS: This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital. RESULTS: 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU. CONCLUSIONS: ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management.