A Novel SPR Immunosensor Based on Dual Signal Amplification Strategy for Detection of SARS-CoV-2 Nucleocapsid Protein.

Since the global outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly around the world. The nucleocapsid (N) protein is one of the most abundant SARS-CoV-2 proteins. Therefore, a sensitive and effective detection method for SARS-CoV-2 N protein is the focus of research. Here, we developed a surface plasmon resonance (SPR) biosensor based on the dual signal-amplification strategy of Au@Ag@Au nanoparticles (NPs) and graphene oxide (GO). Additionally, a sandwich immunoassay was utilized to sensitively and efficiently detect SARS-CoV-2 N protein. On the one hand, Au@Ag@Au NPs have a high refractive index and the capability to electromagnetically couple with the plasma waves propagating on the surface of gold film, which are harnessed for amplifying the SPR response signal. On the other hand, GO, which has the large specific surface area and the abundant oxygen-containing functional groups, could provide unique light absorption bands that can enhance plasmonic coupling to further amplify the SPR response signal. The proposed biosensor could efficiently detect SARS-CoV-2 N protein for 15 min and the detection limit for SARS-CoV-2 N protein was 0.083 ng/mL, with a linear range of 0.1 ng/mL~1000 ng/mL. This novel method can meet the analytical requirements of artificial saliva simulated samples, and the developed biosensor had a good anti-interference capability.

A living WHO guideline on drugs for covid-19

UPDATES: This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19? CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19. NEW OR UPDATED RECOMMENDATIONS: • Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use. UNDERSTANDING THE NEW RECOMMENDATIONS: When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted. PRIOR RECOMMENDATIONS: • Recommended for patients with severe or critical covid-19­strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation­a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19­a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation­a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19­a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity­a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial. ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline.

A Study of the Detection of SARS-CoV-2 by the Use of Electrochemiluminescent Biosensor Based on Asymmetric Polymerase Chain Reaction Amplification Strategy.

A new and reliable method has been constructed for detecting severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) open reading frames 1ab (ORF1ab) gene via highly sensitive electrochemiluminescence (ECL) biosensor technology based on highly efficient asymmetric polymerase chain reaction (asymmetric PCR) amplification strategy. This method uses magnetic particles coupled with biotin-labeled one complementary nucleic acid sequence of the SARS-CoV-2 ORF1ab gene as the magnetic capture probes, and [Formula: see text]-labeled amino-modified another complementary nucleic acid sequence as the luminescent probes, and then a detection model of magnetic capture probes-asymmetric PCR amplification nucleic acid products-[Formula: see text]-labeled luminescent probes is formed, which combines the advantages of highly efficient asymmetric PCR amplification strategy and highly sensitive ECL biosensor technology, enhancing the method sensitivity of detecting the SARS-CoV-2 ORF1ab gene. The method enables the rapid and sensitive detection of the ORF1ab gene and has a linear range of 1-[Formula: see text] copies/[Formula: see text], a regression equation of [Formula: see text] = [Formula: see text] + 2919.301 ([Formula: see text] = 0.9983, [Formula: see text] = 7), and a limit of detection (LOD) of 1 copy/[Formula: see text]. In summary, it can meet the analytical requirements for simulated saliva and urine samples and has the benefits of easy operation, reasonable reproducibility, high sensitivity, and anti-interference abilities, which can provide a reference for developing efficient field detection methods for SARS-CoV-2.

Newly Proposed Diagnostic Criteria for Acute Respiratory Distress Syndrome: Does Inclusion of High Flow Nasal Cannula Solve the Problem?

Acute respiratory distress syndrome (ARDS) is a common life-threatening clinical syndrome which accounts for 10% of intensive care unit admissions. Since the Berlin definition was developed, the clinical diagnosis and therapy have changed dramatically by adding a minimum positive end-expiratory pressure (PEEP) to the assessment of hypoxemia compared to the American-European Consensus Conference (AECC) definition in 1994. High-flow nasal cannulas (HFNC) have become widely used as an effective respiratory support for hypoxemia to the extent that their use was proposed in the expansion of the ARDS criteria. However, there would be problems if the diagnosis of a specific disease or clinical syndrome occurred, based on therapeutic strategies.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

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).

Awake prone positioning for patients with COVID-19 pneumonia in intensive care unit: A systematic review and meta-analysis.

Background: Awake prone positioning (APP) has been widely used in non-intubated COVID-19 patients during the pandemic. However, high-quality evidence to support its use in severe COVID-19 patients in an intensive care unit (ICU) is inadequate. Therefore, we aimed to assess the efficacy and safety of APP for intubation requirements and other important outcomes in this patient population. Methods: We searched for potentially relevant articles in PubMed, Embase, and the Cochrane database from inception to May 25, 2022. Studies focusing on COVID-19 adults in ICU who received APP compared to controls were included. The primary outcome was the intubation requirement. Secondary outcomes were mortality, ICU stay, and adverse events. Study quality was independently assessed, and we also conducted subgroup analysis, sensitivity analysis, and publication bias to explore the potential influence factors. Results: Ten randomized controlled trials with 1,686 patients were eligible. The quality of the included studies was low to moderate. Overall, the intubation rate was 35.2% in the included patients. The mean daily APP duration ranged from <6 to 9 h, with poor adherence to APP protocols. When pooling, APP significantly reduced intubation requirement (risk ratio [RR] 0.84; 95%CI, 0.74-0.95; I 2 = 0%, P = 0.007). Subgroup analyses confirmed the reduced intubation rates in patients who were older (≥60 years), obese, came from a high mortality risk population (>20%), received HFNC/NIV, had lower SpO2/FiO2 (<150 mmHg), or undergone longer duration of APP (≥8 h). However, APP showed no beneficial effect on mortality (RR 0.92 [95% CI 0.77-1.10; I 2 = 0%, P = 0.37] and length of ICU stay (mean difference = -0.58 days; 95% CI, -2.49 to 1.32; I 2 = 63%; P = 0.55). Conclusion: APP significantly reduced intubation requirements in ICU patients with COVID-19 pneumonia without affecting the outcomes of mortality and ICU stay. Further studies with better APP protocol adherence will be needed to define the subgroup of patients most likely to benefit from this strategy.

Establishment of a Duplex Real Time PCR Method for Detection of SARS-COV-2

To quickly and efficiently detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent and control the spread of novel coronavirus disease (COVID-19), a highly sensitive duplex real-time PCR (RT-PCR) detection method has been established. In this study, the specificity of primers and probes were designed, respectively, according to the ORF1ab gene and N gene sequence of SARS-COV-2, and fluorescent probes were labeled with carboxyl fluorescein (FAM) and green fluorescent protein (VIC). The duplex RT-PCR method for detecting SARS-COV-2 with TaqMan probe was established, which has a limit of detection of 10 copies/µL, and the linear detection range of ORF1ab and N gene were 1.0 × 101-1.0 × 105 copies/µL and 1.0 × 101-1.0 × 106 copies/µL, respectively, realizing the simultaneous detection of ORF1ab and N genes in simulated SARS-COV-2 samples. The method has high sensitivity, accurate quantification, simple operation, and cost-saving, which can be used for rapid and efficient quantitative detection of SARS-COV-2.

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).

Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19.

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females. SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces. PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females. CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial.

Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase 2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on day 28 since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator-free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in the JS016 group and 98 in the control group) were analyzed. Most patients, 95 (96%) in the JS016 group and 97 (99%) in the control group were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03 to 3.19; P = 0.33). Few adverse events occurred in both groups (3% in the JS016 group and 1% in the control group, respectively; P = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.).

A Study of the Detection of SARS-CoV-2 ORF1ab Gene by the Use of Electrochemiluminescent Biosensor Based on Dual-Probe Hybridization.

To satisfy the need to develop highly sensitive methods for detecting the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and further enhance detection efficiency and capability, a new method was created for detecting SARS-CoV-2 of the open reading frames 1ab (ORF1ab) target gene by a electrochemiluminescence (ECL) biosensor based on dual-probe hybridization through the use of a detection model of "magnetic capture probes-targeted nucleic acids-Ru(bpy)32+ labeled signal probes". The detection model used magnetic particles coupled with a biotin-labeled complementary nucleic acid sequence of the SARS-CoV-2 ORF1ab target gene as the magnetic capture probes and Ru(bpy)32+ labeled amino modified another complementary nucleic acid sequence as the signal probes, which combined the advantages of the highly specific dual-probe hybridization and highly sensitive ECL biosensor technology. In the range of 0.1 fM~10 µM, the method made possible rapid and sensitive detection of the ORF1ab gene of the SARS-CoV-2 within 30 min, and the limit of detection (LOD) was 0.1 fM. The method can also meet the analytical requirements for simulated samples such as saliva and urine with the definite advantages of a simple operation without nucleic acid amplification, high sensitivity, reasonable reproducibility, and anti-interference solid abilities, expounding a new way for efficient and sensitive detection of SARS-CoV-2.

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.

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

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.

The story of critical care in Asia: a narrative review.

BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.