Epidemiology and Outcomes of Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: A Multicenter Retrospective Study.

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. METHODS: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. RESULTS: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147-13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011-19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723-119.129; p < 0.001). CONCLUSION: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.

Extracorporeal Membrane Oxygenation (ECMO) in Critically Ill Patients with Coronavirus Disease 2019 (COVID-19) Pneumonia and Acute Respiratory Distress Syndrome (ARDS).

Traced back to December 2019, an unexpected outbreak of a highly contagious new coronavirus pneumonia (COVID-19) has rapidly swept around China and the globe. There have now been an estimated 2 580 000 infections and more than 170 000 fatal cases around the world. The World Health Organization (WHO) estimated that approximately 14% of infections developed into severe disease, 5% were critically ill, and the mortality rate of critically ill patients is reported to be over 50%. The shortage of specific anti-viral treatment and vaccines remains a huge challenge. In COVID-19, refractory hypoxemia is common among the critically ill with acute respiratory distress syndrome (ARDS) despite invasive mechanical ventilation, and is further complicated by respiratory and circulatory failure. This difficult situation calls for the use of extracorporeal membrane oxygenation (ECMO) for assisting respiration and circulation if necessary. This article reviews the pertinent clinical literature, technical guidance, and expert recommendations on use of ECMO in critically ill cases of COVID-19. Here, we present basic knowledge and opinions about COVID-19 and ECMO, review the evidence on ECMO use in Middle East Respiratory Syndrome (MERS) and H1N1 influenza, share the technical guidance and recommendations on use of ECMO in COVID-19, summarize the current use of ECMO against COVID-19 in China, and discuss the issues in use of ECMO in COVID-19.

A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients.

INTRODUCTION: Coronavirus disease 2019 (COVID­19) caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection spread worldwide. OBJECTIVES: The aim of the study was to identify the clinical characteristics and risk factors associated with severe incidence of SARS ­CoV­2 infection. PATIENTS AND METHODS: All adult patients (median [IQR] age, 52 [37-58] years) consecutively admitted to the Dabieshan Medical Center from January 30, 2020 to February 11, 2020 were collected and reviewed. Only patients diagnosed with COVID­19  according to the World Health Organization interim guidance were included in this retrospective cohort study. RESULTS: A total of 108 patients with COVID­19 were retrospectively analyzed. Twenty­five patients (23.1%) developed severe disease, and of those 12 patients (48%) died. Advanced age, comorbidities (most commonly hypertension), higher blood leukocyte count, neutrophil count, higher C­reactive protein level, D­dimer level, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score were associated with greater risk of COVID­19, and so were lower lymphocyte count and albumin level. Multivariable regress ion showed increasing odds of severe COVID­19 associated with higher SOFA score (odds ratio [OR], 2.45; 95% CI, 1.302-4.608; P = 0.005), and lymphocyte count less than 0.8 × 109/l (OR, 9.017; 95% CI, 2.808-28.857; P <0.001) on admission. Higher SOFA score (OR, 2.402; 95% CI, 1.313-4.395; P = 0.004) on admission was identified as risk factor for in­hospital death. CONCLUSIONS: Lymphocytopenia and a higher SOFA score on admission could help clinicians to identify patients at high risk for developing severe COVID­19. More related studies are needed in the future.

Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.

SARS-CoV-2 RNA reference materials

Coronavirus disease (COVID-19) is an acute infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reverse transcription real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was the firstly authorized method for the detection of SARS-CoV-2 RNA. As this method is sensitive, specific, it has been widely recognized as the golden standard for the diagnosis of COVID-19. Unfortunately, several false-negative cases have been reported after the outbreak of COVID-19, probably due to the quality of the kits or the improper operation of RT-qPCR. Nucleic acid reference materials (RM) are the key element for the metrology traceability and quality control of SARS-CoV-2 RNA detection, but the development of RNA RM remains a challenge in the biology metrology field. Two main problems are the low stability of the RNA sample and the lack of proven absolute quantification methods. To establish the measurement traceability for SARS-CoV-2 RNA detection, a novel RNA reference material (RM) was developed. The RM is a mixed solution of 3 in vitro transcribed RNA molecules which cover different key target sequences of SARS-CoV-2 gene: The full-length of nucleoprotein (N) gene (28274-29533, GenBank: MT027064.1), the full-length of envelope protein (E) gene (26245-26472, GenBank: MT027064.1), and partial sequence of open reading frame 1ab (ORF1ab) (13321-15540, GenBank: MT027064.1). The purity of the transcribed RNA molecules was verified by a biological analyzer. The results showed that the molecular length of all the RNA molecules were consistent with our design. The clear peaks of our RNA RMs strongly demonstrated good purity. For absolute quantification of RNA RMs, we studied digital PCR (dPCR) for RNA samples. Digital PCR evenly partitioned the sample and PCR reaction solution to a very large number of units, on a microporous chip or in the liquid droplets, etc. After a PCR amplification reaction, the fluorescence signal was detected for each unit individually, with a binary readout of "0" or "1" for negative and positive results respectively. Through the statistics of positive results based on the Poisson distribution, the copy number of RNA sample was accurately determined without standard curves needed. Digital PCR has significantly higher reliability and accuracy. Mainly based on the PCR primers and probes for SARS-CoV-2 detection suggested by the Chinese CDC and WHO, we optimized the key factors of dPCR towards improved amplification efficiency. Through digital PCR measurements by 4 laboratories, the certified values of concentration (copies/mu L) were assigned for the N gene, E gene, and ORF1ab gene in the mixed RM. Single-stranded RNA is unstable and easy to be degraded by RNase in the environment, thus the optimization of RNA protectants is very important for the stability of RNA RMs. During the study of the stability, we found that a proper protector (1 mmol/L DTT and 0.5 U/L Rnase Inhibitor) can effectively increase the valid storage life of our RNA RM. Based on the latest data, the concentration of our RNA RMs was stable for at least 30 d under -80 degrees C storage and 13 d under -4 degrees C storage. In order to verify the applicability of our RNA RM in the actual virus detection process, we analyzed our RMs using 9 SARS-CoV-2 nucleic acid detection kits. These virus RNA detection kits were from different manufacturers with various detection principles, that are being applied in laboratories for virus detection. Finally, our RNA RMs showed high generalizability among 9 kits. The development of RNA RM provides the metrological basis for the quality control of SARS-CoV-2 detection kits.