Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process (preprint)

The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas CD4_CTL precursors were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift- myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model, PHARE (https://xiazlab.org/phare/), which applies to both scRNA-seq and bulk RNA-seq data. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

The city-wide full-scale interactive application of sewage surveillance programme for assisting real-time COVID-19 pandemic control - A case study in Hong Kong.

The paper discusses the implementation of Hong Kong's tailor-made sewage surveillance programme led by the Government, which has demonstrated how an efficient and well-organized sewage surveillance system can complement conventional epidemiological surveillance to facilitate the planning of intervention strategies and actions for combating COVID-19 pandemic in real-time. This included the setting up of a comprehensive sewerage network-based SARS-CoV-2 virus surveillance programme with 154 stationary sites covering 6 million people (or 80 % of the total population), and employing an intensive monitoring programme to take samples from each stationary site every 2 days. From 1 January to 22 May 2022, the daily confirmed case count started with 17 cases per day on 1 January to a maximum of 76,991 cases on 3 March and dropped to 237 cases on 22 May. During this period, a total of 270 "Restriction-Testing Declaration" (RTD) operations at high-risk residential areas were conducted based on the sewage virus testing results, where over 26,500 confirmed cases were detected with a majority being asymptomatic. In addition, Compulsory Testing Notices (CTN) were issued to residents, and the distribution of Rapid Antigen Test kits was adopted as alternatives to RTD operations in areas of moderate risk. These measures formulated a tiered and cost-effective approach to combat the disease in the local setting. Some ongoing and future enhancement efforts to improve efficacy are discussed from the perspective of wastewater-based epidemiology. Forecast models on case counts based on sewage virus testing results were also developed with R2 of 0.9669-0.9775, which estimated that up to 22 May 2022, around 2,000,000 people (~67 % higher than the total number of 1,200,000 reported to the health authority, due to various constraints or limitations) had potentially contracted the disease, which is believed to be reflecting the real situation occurring in a highly urbanized metropolis like Hong Kong.

The Psychometric Properties of the DASS-21 and Its Association with Problematic Internet Use among Chinese College Freshmen.

During transitional periods, college freshmen may experience mental health issues. The Depression, Anxiety, and Stress Scale-21-item version (DASS-21) is commonly used for mental health assessment in China. However, evidence is lacking regarding its applicability with freshmen as a demographic. Debates also exist regarding its factor structure. This study aimed to evaluate the DASS-21's psychometric properties with Chinese college freshmen and investigate its association with three kinds of problematic Internet use. A convenience sampling method was used to recruit two samples of freshmen-one of 364 (female 248; mean age 18.17 years) and the other of 956 (female 499; mean age 18.38 years) participants. McDonald's ω and confirmatory factor analysis were conducted to evaluate both the scale's internal reliability and construct validity. The results indicated acceptable reliability, with a one-factor structure inferior to a three-factor structure in terms of model fit. Furthermore, it was demonstrated that problematic Internet use was significantly and positively associated with depression, anxiety, and stress among Chinese college freshmen. Based on the prerequisite of measurement equivalence across two samples, the study also found that freshmen's problematic Internet use and psychological distress were likely to be affected by the strict measures put in place during the COVID-19 pandemic.

The Joint Effects of Social Norm Appeals and Fear Appeals in COVID-19 Vaccine Campaign Posters on Self-Perceived Communication Quality and Vaccination Intention

To understand how different types of cues in vaccine education messages affect attitude toward campaign messages and vaccination intention, this study examined the impact of the presence of social norm appeals (individual vs. group cues) and the presence of fear appeals in coronavirus disease 2019 (COVID-19) vaccine campaign posters on perceived communication quality and vaccination intention. A 2 (social norm appeal: individual cue vs. group cue) × 2 (fear appeal: absence vs. presence) × 3 (repetition) within-subject factorial design experiment was conducted in China. Findings demonstrated that the presence of fear appeals in COVID-19 vaccine campaign posters elicited lower levels of perceived communication quality and vaccination intention than those without fear appeals. The interactive effect of fear appeals and social norm appeals was also found to be significant. Specifically, positive-framed messages (i.e., absence of fear appeals) with group cues and fear appeal messages with individual cues elicited higher perceived information quality and stronger vaccination intention than other types of messages. Understanding how these cues function jointly in COVID-19 vaccine campaign messages will help public health practitioners create more effective intervention strategies.

A Study on the College Students' Employment Psychological Problems and Countermeasures in the Regular Prevention and Control of COVID-19--From the Perspective of Positive Psychology

With the normalization of epidemic prevention and control of COVID-19, the psychological problems of college students' employment have become more prominent. In this situation, college students' employment psychological problems are more complex than before, which to a large extent affects the students' employment psychology, employment objectives, but also affects the society's accurate selection of talents. This paper expounds the employment psychological problems of college students, from the perspective of positive psychology based on prevention, put forward coping strategies, to help college students to successfully complete the psychological adaptation and identity transformation from school to society, to achieve employment.

A Randomized, Single-Blind, Group Sequential, Active-Controlled Study to Evaluate the Clinical Efficacy and Safety of α-Lipoic Acid for Critically Ill Patients With Coronavirus Disease 2019 (COVID-19).

OBJECT: To evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: A randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days. RESULT: Nine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P = 0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P = 0.09). CONCLUSION: In our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=49534.

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.

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.

Elevated Pancreatic Enzymes in ICU Patients With COVID-19 in Wuhan, China: A Retrospective Study.

Background: Pancreatic enzyme elevation has been reported in patients with COVID-19 during the pandemic. However, with the shortage of medical resources and information, several challenges are faced in the examination and treatment of this condition in COVID-19 patients. There is little information on whether such condition is caused by pancreatic injury, and if this is a warning sign of life threatening complications like multiple organ failure in patients. The objective of this study is to explore the relationship between elevated pancreatic enzymes and the underlying risk factors during the management of COVID-19 patients. Method: A total of 55 COVID-19 patients admitted to the intensive care unit (ICU) of Wuhan Jinyintan hospital from January 1 to March 30, 2020 were enrolled in this study. All participants underwent transabdominal ultrasound imaging to assess their pancreas. Results: Out of the 55 patients, three patients had pancreatitis, 29 (52.7%) with elevated pancreatic enzymes, and 23 (41.8%) without. The most common symptoms of patients with COVID-19 were fever and cough. There was no statistical difference in most baseline characteristics except myalgia on admission. Compared with those having normal enzyme levels, patients with elevated pancreatic enzymes had higher rates of mortality (79.3 vs. 52.2%; P = 0.038), and lower rates of discharge (20.7 vs. 47.8%; P = 0.038). Patients with elevated enzymes had higher incidence of mechanical ventilation (P = 0.004) and kidney injury (P = 0.042) than patients without elevated pancreatic enzymes. The results of multivariable logistic analysis showed that the odds ratio were 10.202 (P = 0.002) for mechanical ventilation and 7.673 (P = 0.014) for kidney injury with the elevated enzymes vs. the normal conditions. Conclusions: The findings show that the incidences of pancreatic enzymes elevation are not low in critical COVID-19 patients and only a few of them progressed to acute pancreatitis (AP). Increased pancreatic enzymes levels is associated with poor prognosis in COVID-19 patients. In addition, the kidney injury and oxygenation degradation are associated with the pancreatic enzymes elevation in COVID-19 patients.

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.

Severe COVID-19 has a distinct phenotype from bacterial sepsis: a retrospective cohort study in deceased patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused more than 2 million deaths worldwide. Viral sepsis has been proposed as a description for severe COVID-19, and numerous therapies have been on trials based upon this hypothesis. However, whether the clinical characteristics of severe COVID-19 are similar to those of bacterial sepsis has not been elucidated. METHODS: We retrospectively compared the clinical data of non-surviving COVID-19 patients who were admitted to a 30-bed intensive care unit (ICU) in Wuhan Infectious Diseases Hospital (Wuhan, China) from 22 January 2020, to 28 February 2020, with those of non-surviving patients with bacterial sepsis who were admitted to the ICU in Zhongshan Hospital, Fudan University (Shanghai, China) from 3 July 2018, to 30 June 2020. RESULTS: A total of 53 COVID-19 patients and 26 septic patients were included in the analysis. The mean ages were 65.6 [standard deviation (SD): 11.1] and 70.4 (SD: 14.3) years in the COVID-19 cohort and sepsis cohort, respectively. The proportion of participants with hypertension was higher in non-survivors with COVID-19 than in non-survivors with sepsis (41.5% vs. 15.4%, P=0.020). The Sequential Organ Failure Assessment (SOFA) score of non-survivors with COVID-19 was lower than that of non-survivors with sepsis at ICU admission {4.0 [interquartile range (IQR): 3.0-6.0] vs. 7.5 [IQR: 5.8-11.0], P<0.001}. The clinical parameters at ICU admission assessed with principal component analysis and hierarchical cluster analysis showed that COVID-19 patients were distinct from bacterial septic patients. Compared with non-survivors with sepsis, non-survivors with COVID-19 had a higher neutrophil/lymphocyte ratio, total protein, globulin, lactate dehydrogenase (LDH), and D-dimer; a lower eosinophil count, procalcitonin, interleukin-6 (IL-6), total bilirubin, direct bilirubin, myohemoglobin, albumin/globulin ratio, activated partial thromboplastin time (APTT), prothrombin time (PT), and international normalization ratio (INR) at ICU admission. In addition, the levels of total protein, globulin, LDH, D-dimer, and IL-6 were significantly different between the two groups during the ICU stay. CONCLUSIONS: Patients with critical COVID-19 have a phenotype distinct from that of patients with bacterial sepsis. Therefore, caution should be used when applying the previous experience of bacterial sepsis to patients with severe COVID-19.

Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study.

BACKGROUND: A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. METHODS: Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). RESULTS: Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). CONCLUSION: Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.

Association of D-dimer elevation with inflammation and organ dysfunction in ICU patients with COVID-19 in Wuhan, China: a retrospective observational study.

Coronavirus disease 2019 (COVID-19)-associated coagulation dysfunction is gaining attention. In particular, dynamic changes in the D-dimer level may be related to disease progression. Here, we explored whether elevated D-dimer level was related to multiple organ failure and a higher risk of death. This study included 158 patients with COVID-19 who were admitted to the intensive care unit (ICU) at Jinyintan Hospital in Wuhan, China between January 20, 2020 and February 26, 2020. Clinical and laboratory data were collected. The relationship between D-dimer elevation and organ dysfunction was analyzed, as were dynamic changes in inflammation and lipid metabolism. Approximately 63.9% of patients with COVID-19 had an elevated D-dimer level on ICU admission. The 14 day ICU mortality rate was significantly higher in patients with a high D-dimer level than in those with a normal D-dimer level. Patients with a D-dimer level of 10-40µg/mL had similar organ function on ICU admission to those with a D-dimer level of 1.5-10µg/mL. However, patients with higher levels of D-dimer developed organ injuries within 7 days. Furthermore, significant differences in inflammation and lipid metabolism markers were observed between the two groups. In conclusion, the D-dimer level is closely related to COVID-19 severity and might influence the likelihood of rapid onset of organ injury after admission.

Lung Recruitment, Individualized PEEP, and Prone Position Ventilation for COVID-19-Associated Severe ARDS: A Single Center Observational Study.

Background: Patients with coronavirus disease 2019 (COVID-19) may develop severe acute respiratory distress syndrome (ARDS). The aim of the study was to explore the lung recruitability, individualized positive end-expiratory pressure (PEEP), and prone position in COVID-19-associated severe ARDS. Methods: Twenty patients who met the inclusion criteria were studied retrospectively (PaO2/FiO2 68.0 ± 10.3 mmHg). The patients were ventilated under volume-controlled mode with tidal volume of 6 mL/kg predicted body weight. The lung recruitability was assessed via the improvement of PaO2, PaCO2, and static respiratory system compliance (Cstat) from low to high PEEP (5-15 cmH2O). Patients were considered recruitable if two out of three parameters improved. Subsequently, PEEP was titrated according to the best Cstat. The patients were turned to prone position for further 18-20 h. Results: For recruitability assessment, average value of PaO2 was slightly improved at PEEP 15 cmH2O (68.0 ± 10.3 vs. 69.7 ± 7.9 mmHg, baseline vs. PEEP 15 cmH2O; p = 0.31). However, both PaCO2 and Cstat worsened (PaCO2: 72.5 ± 7.1 vs. 75.1 ± 9.0 mmHg; p < 0.01. Cstat: 17.5 ± 3.5 vs. 16.6 ± 3.9 ml/cmH2O; p = 0.05). Only four patients (20%) were considered lung recruitable. Individually titrated PEEP was higher than the baseline PEEP (8.0 ± 2.1 cmH2O vs. 5 cmH2O, p < 0.001). After 18-20 h of prone positioning, investigated parameters were significantly improved compared to the baseline (PaO2: 82.4 ± 15.5 mmHg. PaCO2: 67.2 ± 6.4 mmHg. Cstat: 20.6 ± 4.4 ml/cmH2O. All p < 0.001 vs. baseline). Conclusions: Lung recruitability was very low in COVID-19-associated severe ARDS. Individually titrated PEEP and prone positioning might improve lung mechanics and blood gasses.

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.

Coagulation dysfunction in ICU patients with coronavirus disease 2019 in Wuhan, China: a retrospective observational study of 75 fatal cases.

Coagulation dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19) has not been well described, and the efficacy of anticoagulant therapy is unclear. In this study, we retrospectively reviewed 75 fatal COVID-19 cases who were admitted to the intensive care unit at Jinyintan Hospital (Wuhan, China). The median age of the cases was 67 (62-74) years, and 47 (62.7%) were male. Fifty patients (66.7%) were diagnosed with disseminated intra-vascular coagulation. Approximately 90% of patients had elevated D-dimer and fibrinogen degradation products, which decreased continuously after anticoagulant treatment and was accompanied by elevated albumin (all P<0.05). The median survival time of patients treated with anticoagulant was 9.0 (6.0-14.0) days compared with 7.0 (3.0-10.0) days in patients without anticoagulant therapy (P=0.008). After anticoagulation treatment, C-reactive protein levels decreased (P=0.004), as did high-sensitivity troponin (P=0.018), lactate dehydrogenase (P<0.001), and hydroxybutyrate dehydrogenase (P<0.001). In conclusion, coagulation disorders were widespread among fatal COVID-19 cases. Anticoagulant treatment partially improved hypercoagulability, prolonged median survival time, and may have postponed inflammatory processes and cardiac injury.

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.

Effects of the Lower Airway Secretions on Airway Opening Pressures and Suction Pressures in Critically Ill COVID-19 Patients: A Computational Simulation.

In patients with critically ill COVID-19 pneumonia, lower airways are filled with plenty of highly viscous exudates or mucus, leading to airway occlusion. The estimation of airway opening pressures and effective mucus clearance are therefore two issues that clinicians are most concerned about during mechanical ventilation. In this study we retrospectively analyzed respiratory data from 24 critically ill patients with COVID-19 who received invasive mechanical ventilation and recruitment maneuver at Jinyintan Hospital in Wuhan, China. Among 24 patients, the mean inspiratory plateau pressure was 52.4 ± 4.4 cmH2O (mean ± [SD]). Particularly, the capnograms presented an upward slope during the expiratory plateau, indicting the existence of airway obstruction. A computational model of airway opening was subsequently introduced to investigate possible fluid dynamic mechanisms for the extraordinarily high inspiratory plateau pressures among these patients. Our simulation results showed that the predicted airway opening pressures could be as high as 40-50 cmH2O and the suction pressure could exceed 20 kPa as the surface tension and viscosity of secretion simulants markedly increased, likely causing the closures of the distal airways. We concluded that, in some critically ill patients with COVID-19, limiting plateau pressure to 30 cmH2O may not guarantee the opening of airways due to the presence of highly viscous lower airway secretions, not to mention spontaneous inspiratory efforts. Active airway humidification and effective expectorant drugs are therefore strongly recommended during airway management.

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.