Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. METHODS: This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). DISCUSSION: As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. TRIAL REGISTRATION: ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

An expanded definition of acute respiratory distress syndrome: Challenging the status quo.

Although the Berlin definition of acute respiratory distress syndrome (ARDS), 2012 has been widely used in clinical practice, issues have occasionally been raised regarding various criteria since it was proposed. High-flow nasal oxygen (HFNO) is widely used for effective respiratory support in acute respiratory failure. As patients who do not require ventilation but meet the Berlin criteria have similar characteristics to those with ARDS, the definition of ARDS may be broadened to include patients receiving HFNO. As the PaO2/FiO2 under-recognizes the diagnosis of ARDS, a SpO2/FiO2 value of ≤315 may be considered instead of a PaO2/FiO2 value of ≤300 for diagnosing the condition in resource-constrained settings. In this context, patients with severe COVID-19 always meet other criteria for ARDS except for 7-day acute onset. Therefore, the timeframe for the onset of ARDS may be extended to up to 14 days. An expanded definition of ARDS may allow early identification of patients with less severe diseases and facilitate testing and application of new therapies in patients with a high risk of poor outcomes. Here, we discuss the major controversies regarding the extension of the ARDS definition with a view to improving clinical implementation and patient outcomes.

It is time to update the ARDS definition: It starts with COVID-19-induced respiratory failure.

Coronavirus disease 2019 (COVID-19) may rapidly worsen respiratory failure, thereby leading to death. COVID-19-induced respiratory failure exhibits some atypical characteristics, silent hypoxemia, and high lung compliance. Some histopathological changes associated with COVID-19-induced respiratory failure differ from those of classic acute respiratory distress syndrome (ARDS). However, compared with classical ARDS, COVID-19-induced respiratory failure has a similar timing of onset, clinical syndromes, radiological profile, and mortality rate in the intensive care unit (ICU). Respiratory failure induced by COVID-19 is a type of ARDS and is currently underdiagnosed. This condition stretches the definition of classic ARDS; therefore, an updated definition is warranted.

Predicting the Number of Reported Pulmonary Tuberculosis in Guiyang, China, Based on Time Series Analysis Techniques.

Tuberculosis (TB) is one of the world's deadliest infectious disease killers today, and despite China's increasing efforts to prevent and control TB, the TB epidemic is still very serious. In the context of the COVID-19 pandemic, if reliable forecasts of TB epidemic trends can be made, they can help policymakers with early warning and contribute to the prevention and control of TB. In this study, we collected monthly reports of pulmonary tuberculosis (PTB) in Guiyang, China, from January 1, 2010 to December 31, 2020, and monthly meteorological data for the same period, and used LASSO regression to screen four meteorological factors that had an influence on the monthly reports of PTB in Guiyang, including sunshine hours, relative humidity, average atmospheric pressure, and annual highest temperature, of which relative humidity (6-month lag) and average atmospheric pressure (7-month lag) have a lagging effect with the number of TB reports in Guiyang. Based on these data, we constructed ARIMA, Holt-Winters (additive and multiplicative), ARIMAX (with meteorological factors), LSTM, and multivariable LSTM (with meteorological factors). We found that the addition of meteorological factors significantly improved the performance of the time series prediction model, which, after comprehensive consideration, included the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months at the average atmospheric pressure, outperforms the other models in terms of both fit (RMSE = 37.570, MAPE = 10.164%, MAE = 28.511) and forecast sensitivity (RMSE = 20.724, MAPE = 6.901%, MAE = 17.306), so the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months can be used as a predictor tool for predicting the number of monthly reports of PTB in Guiyang, China.

The Efficiency of Convalescent Plasma Therapy in the Management of Critically Ill Patients Infected With COVID-19: A Matched Cohort Study.

Background: The convalescent plasma of patients who recover from coronavirus disease 2019 (COVID-19) contains high titers of neutralizing antibodies, which has potential effects on the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and improving the prognosis of patients with COVID-19. The goal of this study was to clarify the effects of convalescent plasma therapy on the 60-day mortality and negative conversion rate of SARS-CoV-2 during the hospitalization of patients with severe and life-threatening COVID-19 infection. Methods: This was a retrospective, case-matched cohort study that involved patients with severe COVID-19 infections. The patients who received convalescent plasma therapy were matched by age, sex, diabetes, hypertension, heart failure, the onset of symptoms to hospital admission, respiratory support pattern, lymphocyte count, troponin, Sequential organ failure assessment (SOFA), glucocorticoid, and antiviral agents to no more than three patients with COVID-19 who did not receive convalescent plasma therapy. A Cox regression model and competing risk analysis were used to evaluate the effects of convalescent plasma therapy on these patients. Results: Twenty-six patients were in the convalescent plasma therapy group, and 78 patients were in the control group. Demographic characteristics were similar in both groups, except for the SOFA score. Convalescent plasma therapy did not improve 60-day mortality [hazard ratio (HR) 1.44, 95% CI 0.82-2.51, p = 0.20], but the SARS-CoV-2 negative conversion rate for 60 days after admission was higher in the convalescent plasma group (26.9 vs. 65.4%, p = 0.002) than in the control. Then, a competing risk analysis was performed, which considered events of interest (the negative conversion rate of SARS-CoV-2) and competing events (death) in the same model. Convalescent plasma therapy improved events of interest (p = 0.0002). Conclusion: Convalescent plasma therapy could improve the SARS-CoV-2 negative conversion rate but could not improve 60-day mortality in patients with severe and life-threatening COVID-19 infection. Clinical Trial Number: The study was registered at ClinicalTrials.gov (NCT04616976).

The Efficiency of Convalescent Plasma Therapy in the Management of Critically Ill Patients Infected With COVID-19: A Matched Cohort Study

Background The convalescent plasma of patients who recover from coronavirus disease 2019 (COVID-19) contains high titers of neutralizing antibodies, which has potential effects on the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and improving the prognosis of patients with COVID-19. The goal of this study was to clarify the effects of convalescent plasma therapy on the 60-day mortality and negative conversion rate of SARS-CoV-2 during the hospitalization of patients with severe and life-threatening COVID-19 infection. Methods This was a retrospective, case-matched cohort study that involved patients with severe COVID-19 infections. The patients who received convalescent plasma therapy were matched by age, sex, diabetes, hypertension, heart failure, the onset of symptoms to hospital admission, respiratory support pattern, lymphocyte count, troponin, Sequential organ failure assessment (SOFA), glucocorticoid, and antiviral agents to no more than three patients with COVID-19 who did not receive convalescent plasma therapy. A Cox regression model and competing risk analysis were used to evaluate the effects of convalescent plasma therapy on these patients. Results Twenty-six patients were in the convalescent plasma therapy group, and 78 patients were in the control group. Demographic characteristics were similar in both groups, except for the SOFA score. Convalescent plasma therapy did not improve 60-day mortality [hazard ratio (HR) 1.44, 95% CI 0.82–2.51, p = 0.20], but the SARS-CoV-2 negative conversion rate for 60 days after admission was higher in the convalescent plasma group (26.9 vs. 65.4%, p = 0.002) than in the control. Then, a competing risk analysis was performed, which considered events of interest (the negative conversion rate of SARS-CoV-2) and competing events (death) in the same model. Convalescent plasma therapy improved events of interest (p = 0.0002). Conclusion Convalescent plasma therapy could improve the SARS-CoV-2 negative conversion rate but could not improve 60-day mortality in patients with severe and life-threatening COVID-19 infection. Clinical Trial Number The study was registered at ClinicalTrials.gov (NCT04616976).

Intravenous Immunoglobulin Therapy for Critically Ill COVID-19 Patients With Different Inflammatory Phenotypes: A Multicenter, Retrospective Study.

Background: The benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients. Methods: We analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis. Results: Between January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes. Conclusion: No significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Delayed Initiation of ECMO Is Associated With Poor Outcomes in Patients With Severe COVID-19: A Multicenter Retrospective Cohort Study.

Background: Extracorporeal membrane oxygenation (ECMO) is a rapidly evolving therapy for acute lung and/or heart failure. However, the information on the application of ECMO in severe coronavirus disease 2019 (COVID-19) is limited, such as the initiation time. Especially in the period and regions of ECMO instrument shortage, not all the listed patients could be treated with ECMO in time. This study aimed to investigate and clarify the timing of ECMO initiation related to the outcomes of severe patients with COVID-19. The results show that ECMO should be initiated within 24 h after the criteria are met. Methods: In this retrospective, multicenter cohort study, we enrolled all ECMO patients with confirmed COVID-19 at the three hospitals between December 29, 2019 and April 5, 2020. Data on the demographics, clinical presentation, laboratory profile, clinical course, treatments, complications, and outcomes were collected. The primary outcomes were successful ECMO weaning rate and 60-day mortality after ECMO. Successful weaning from ECMO means that the condition of patients improved with adequate oxygenation and gas exchange, as shown by the vital signs, blood gases, and chest X-ray, and the patient was weaned from ECMO for at least 48 h. Results: A total of 31 patients were included in the analysis. The 60-day mortality rate after ECMO was 71%, and the ECMO weaning rate was 26%. Patients were divided into a delayed ECMO group [3 (interquartile range (IQR), 2-5) days] and an early ECMO group [0.5 (IQR, 0-1) days] based on the time between meeting the ECMO criteria and ECMO initiation. In this study, 14 and 17 patients were included in the early and delayed treatment groups, respectively. Early initiation of ECMO was associated with decreased 60-day mortality after ECMO (50 vs. 88%, P = 0.044) and an increased ECMO weaning rate (50 vs. 6%, P = 0.011). Conclusions: In ECMO-supported patients with COVID-19, delayed initiation of ECMO is a risk factor associated with a poorer outcome. Trial Registration: Clinical trial submission: March 19, 2020. Registry name: A medical records-based study for the clinical application of extracorporeal membrane oxygenation in the treatment of severe respiratory failure patients with novel coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.aspx?proj=51267,identifier:~ChiCTR2000030947.

Secondary infection in severe and critical COVID-19 patients in China: a multicenter retrospective study.

BACKGROUND: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. RESULTS: Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13 days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28-day survival rate. CONCLUSIONS: In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Evaluation of Positive End-Expiratory Pressure Strategies in Patients With Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome.

Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics. Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP-fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2. Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP-FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8). Conclusions: In our cohort with COVID-19-induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04359251.

COVID-19-associated coagulopathy: thromboembolism prophylaxis and poor prognosis in ICU.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases. METHODS: We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020. RESULTS: Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality. CONCLUSIONS: A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.

Neutralizing activity to SARS-CoV-2 of convalescent and control plasma used in a randomized controlled trial.

BACKGROUND: There are limited data on the neutralizing activity of convalescent plasma (CP) administered in randomized controlled trials (RCT) of COVID-19 infection. STUDY DESIGN AND METHODS: As part of an RCT, CP was collected per FDA guidelines from individuals recovered from COVID-19 infection. CP donors had to have ≥145 optical density (OD) units (ideal target ≥300) using a semiquantitative, immunochromatographic test for IgG antibody to the nucleocapsid protein (NP) of SARS-CoV-2 (typical range 0-500 OD units). A random subset of samples [14 control plasma, 12 CP "medium-anti-NP" (145-299 OD units), and 13 CP "high" anti-NP (≥300 OD units)] were tested for neutralizing antibodies using an established viral luciferase antibody inhibition assay to detect the infection of SARS-CoV-2 pseudovirus that encoded spike protein (SARS2-Strunc ) on a human immunodeficiency virus 1 vector (NL43dEnvNanoLuc), using ACE2-expressing 293 T cells. The titer needed to neutralize 50% of viral activity (NT50) was calculated. RESULTS: The uptake of SARS-CoV-2 pseudovirus by 293TACE2 cells was inhibited by pretreatment with CP compared to control CP (p < .001) with control plasma having a median (IQR) 50% neutralization titer (NT50) of 1:28 (1:16,1:36) compared to 1:334 (1:130,1:1295) and 1:324 (1:244,1:578), for medium anti-NP and high anti-NP CP units, respectively. The neutralizing activity of CP met minimum FDA criteria with neutralizing antibody titers >1:80 in 100% of randomly selected samples, using a conservative approach that excluded non-specific binding. DISCUSSION: Plasma from donors screened using an immunochromatographic test for IgG antibody to SARS-CoV-2 NP exhibited neutralizing activity meeting FDA's minimum standard in all randomly selected COVID-19 CP units.

Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier.

Mesenchymal stem cells (MSCs) may improve the treatment of acute respiratory distress syndrome (ARDS). However, few studies have investigated the effects of mechanically stretched -MSCs (MS-MSCs) in in vitro models of ARDS. The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. We introduced a cocultured model of pulmonary microvascular endothelial cell (EC) and MSC medium obtained from MSCs with or without mechanical stretch. We found that Wright-Giemsa staining revealed that MSC morphology changed significantly and cell plasma shrank separately after mechanical stretch. Cell proliferation of the MS-MSC groups was much lower than the untreated MSC group; expression of cell surface markers did not change significantly. Compared to the medium from untreated MSCs, inflammatory factors elevated statistically in the medium from MS-MSCs. Moreover, the paracellular permeability of endothelial cells treated with LPS was restored with a medium from MS-MSCs, while LPS-induced EC apoptosis decreased. In addition, protective effects on the remodeling of intercellular junctions were observed when compared to LPS-treated endothelial cells. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS.

The incidence, risk factors and prognosis of acute kidney injury in severe and critically ill patients with COVID-19 in mainland China: a retrospective study.

BACKGROUND: The clinical correlates, prognosis and determinants of acute kidney injury (AKI) in patients with coronavirus disease 2019 (Covid-19) remain largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. RESULTS: Among 210 patients, 131 were males (62.4%). The median Age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) were classified as being at stage 1, 2 and 3, respectively. 54 patients (58.7%) received continuous renal replacement therapy. Age, sepsis, nephrotoxic drug, invasive mechanical ventilation and elevated baseline serum creatinine levels were associated with the occurrence of AKI. Renal recovery during hospitalization was identified among 16 patients with AKI (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher ratio of partial pressure of oxygen to the fraction of inspired oxygen. Of 210 patients, 93 deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater Age and the lowest ratio of partial pressure of oxygen to the fraction of inspired oxygen being < 150 mmHg were independently associated with death. CONCLUSIONS: Among patients with Covid-19, the incidence of AKI was high. Our findings of the risk factors of the development of AKI and factors associated with renal function recovery may inform clinical management of patients with critical illness of Covid-19.

Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study.

PURPOSE: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. METHODS: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. RESULTS: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO2/FiO2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. CONCLUSION: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.

Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed. METHODS: Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences. RESULTS: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations. CONCLUSION: There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.