Awake prone positioning in acute hypoxaemic respiratory failure.

Awake prone positioning (APP) of patients with acute hypoxaemic respiratory failure gained considerable attention during the early phases of the coronavirus disease 2019 (COVID-19) pandemic. Prior to the pandemic, reports of APP were limited to case series in patients with influenza and in immunocompromised patients, with encouraging results in terms of tolerance and oxygenation improvement. Prone positioning of awake patients with acute hypoxaemic respiratory failure appears to result in many of the same physiological changes improving oxygenation seen in invasively ventilated patients with moderate-severe acute respiratory distress syndrome. A number of randomised controlled studies published on patients with varying severity of COVID-19 have reported apparently contrasting outcomes. However, there is consistent evidence that more hypoxaemic patients requiring advanced respiratory support, who are managed in higher care environments and who can be prone for several hours, benefit most from APP use. We review the physiological basis by which prone positioning results in changes in lung mechanics and gas exchange and summarise the latest evidence base for APP primarily in COVID-19. We examine the key factors that influence the success of APP, the optimal target populations for APP and the key unknowns that will shape future research.

Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP. METHODS: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care. RESULTS: A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) (P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant. CONCLUSIONS: APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients.

A new multiplex SARS-CoV-2 antigen microarray showed correlation of IgG, IgA, and IgM antibodies from patients with COVID-19 disease severity and maintenance of relative IgA and IgM antigen binding over time.

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity different from the same isotype in whole serum, probably due to competition from the other isotypes present. Using purified antibody isotypes from naïve Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with binding to the S region S1 expressed in insect cells (S1 Sf21) significant for IgG, IgA, and IgM. Assessing longitudinal response for constant concentrations of purified antibody isotypes for a patient subset demonstrated that the relative proportion of antigen-specific IgGs decreased over time for severe disease, but the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen-specific serum IgA and IgM playing a role in maintaining longer-term protection, important for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions.

Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies.

BACKGROUND: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic. METHODS: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort. RESULTS: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population. CONCLUSION: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.

The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial.

BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia. METHODS: This is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1ß, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1ß/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP. DISCUSSION: This trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04511923 . Registered on 13 August 2020. Protocol version 8, 22/12/2021 Protocol identifier: NUIG-2020-003 EudraCT registration number: 2020-003349-12 9 October 2020.

Best practice guidance for digital contact tracing apps: A cross-disciplinary review of the literature

Background: Digital contact tracing apps have the potential to augment contact tracing systems and disrupt COVID-19 transmission by rapidly identifying secondary cases prior to the onset of infectiousness and linking them into a system of quarantine, testing, and health care worker case management. The international experience of digital contact tracing apps during the COVID-19 pandemic demonstrates how challenging their design and deployment are. Objective: This study aims to derive and summarize best practice guidance for the design of the ideal digital contact tracing app. Methods: A collaborative cross-disciplinary approach was used to derive best practice guidance for designing the ideal digital contact tracing app. A search of the indexed and gray literature was conducted to identify articles describing or evaluating digital contact tracing apps. MEDLINE was searched using a combination of free-text terms and Medical Subject Headings search terms. Gray literature sources searched were the World Health Organization Institutional Repository for Information Sharing, the European Centre for Disease Prevention and Control publications library, and Google, including the websites of many health protection authorities. Articles that were acceptable for inclusion in this evidence synthesis were peer-reviewed publications, cohort studies, randomized trials, modeling studies, technical reports, white papers, and media reports related to digital contact tracing. Results: Ethical, user experience, privacy and data protection, technical, clinical and societal, and evaluation considerations were identified from the literature. The ideal digital contact tracing app should be voluntary and should be equitably available and accessible. User engagement could be enhanced by small financial incentives, enabling users to tailor aspects of the app to their particular needs and integrating digital contact tracing apps into the wider public health information campaign. Adherence to the principles of good data protection and privacy by design is important to convince target populations to download and use digital contact tracing apps. Bluetooth Low Energy is recommended for a digital contact tracing app's contact event detection, but combining it with ultrasound technology may improve a digital contact tracing app's accuracy. A decentralized privacy-preserving protocol should be followed to enable digital contact tracing app users to exchange and record temporary contact numbers during contact events. The ideal digital contact tracing app should define and risk-stratify contact events according to proximity, duration of contact, and the infectiousness of the case at the time of contact. Evaluating digital contact tracing apps requires data to quantify app downloads, use among COVID-19 cases, successful contact alert generation, contact alert receivers, contact alert receivers that adhere to quarantine and testing recommendations, and the number of contact alert receivers who subsequently are tested positive for COVID-19. The outcomes of digital contact tracing apps' evaluations should be openly reported to allow for the wider public to review the evaluation of the app. Conclusions: In conclusion, key considerations and best practice guidance for the design of the ideal digital contact tracing app were derived from the literature. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial.

BACKGROUND: Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. METHODS: In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). RESULTS: Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. CONCLUSION: In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.

Public opinion of the Irish “COVID Tracker” digital contact tracing App: A national survey

Objective This study aims to gather public opinion on the Irish “COVID Tracker” digital contact tracing (DCT) App, with particular focus on App usage, usability, usefulness, technological issues encountered, and potential changes to the App. Methods A 35-item online questionnaire was deployed for 10 days in October 2020, 3 months after the launch of the Irish DCT App. Results A total of 2889 completed responses were recorded, with 2553 (88%) respondents currently using the App. Although four in five users felt the App is easy to download, is easy to use and looks professional, 615 users (22%) felt it had slowed down their phone, and 757 (28%) felt it had a negative effect on battery life. Seventy-nine percent of respondents reported the App's main function is to aid contact tracing. Inclusion of national COVID-19 trends is a useful ancillary function according to 87% of respondents, and there was an appetite for more granular local data. Overall, 1265 (44%) respondents believed the App is helping the national effort, while 1089 (38%) were unsure. Conclusions DCT Apps may potentially augment traditional contact tracing methods. Despite some reports of negative effects on phone performance, just 7% of users who have tried the App have deleted it. Ancillary functionality, such as up-to-date regional COVID-19, may encourage DCT App use. This study describes general positivity toward the Irish COVID Tracker App among users but also highlights the need for transparency on effectiveness of App-enabled contact tracing and for study of non-users to better establish barriers to use.

Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations. METHODS: In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients (ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285. FINDINGS: A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72-0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71-0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71-0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45-1·69]) or in non-ICU settings (RR 0·88 [0·44-1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome. INTERPRETATION: In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU. FUNDING: OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.

Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies.

There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.

BACKGROUND: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. METHODS: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655. FINDINGS: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. INTERPRETATION: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. FUNDING: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.

Design and Rationale of a Prospective International Follow-Up Study on Intensive Care Survivors of COVID-19: The Long-Term Impact in Intensive Care Survivors of Coronavirus Disease-19-AFTERCOR.

Background: In a disease that has only existed for 18 months, it is difficult to be fully informed of the long-term sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Evidence is growing that most organ systems can be affected by the virus, causing severe disabilities in survivors. The extent of the aftermath will declare itself over the next 5-10 years, but it is likely to be substantial with profound socio-economic impact on society. Methods: This is an international multi-center, prospective long-term follow-up study of patients who developed severe coronavirus disease-2019 (COVID-19) and were admitted to Intensive Care Units (ICUs). The study will be conducted at international tertiary hospitals. Patients will be monitored from time of ICU discharge up to 24 months. Information will be collected on demographics, co-existing illnesses before ICU admission, severity of illness during ICU admission and post-ICU quality of life as well as organ dysfunction and recovery. Statistical analysis will consist of patient trajectories over time for the key variables of quality of life and organ function. Using latent class analysis, we will determine if there are distinct patterns of patients in terms of recovery. Multivariable regression analyses will be used to examine associations between baseline characteristics and severity variables upon admission and discharge in the ICU, and how these impact outcomes at all follow-up time points up to 2 years. Ethics and Dissemination: The core study team and local principal investigators will ensure that the study adheres to all relevant national and local regulations, and that the necessary approvals are in place before a site may enroll patients. Clinical Trial Registration:anzctr.org.au: ACTRN12620000799954.

Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients.

OBJECTIVE: We aimed to characterize the effects of prone positioning on respiratory mechanics and oxygenation in invasively ventilated patients with SARS-CoV-2 ARDS. RESULTS: This was a prospective cohort study in the Intensive Care Unit (ICU) of a tertiary referral centre. We included 20 consecutive, invasively ventilated patients with laboratory confirmed SARS-CoV-2 related ARDS who underwent prone positioning in ICU as part of their management. The main outcome was the effect of prone positioning on gas exchange and respiratory mechanics. There was a median improvement in the PaO2/FiO2 ratio of 132 in the prone position compared to the supine position (IQR 67-228). We observed lower PaO2/FiO2 ratios in those with low (< median) baseline respiratory system static compliance, compared to those with higher (> median) static compliance (P < 0.05). There was no significant difference in respiratory system static compliance with prone positioning. Prone positioning was effective in improving oxygenation in SARS-CoV-2 ARDS. Furthermore, poor respiratory system static compliance was common and was associated with disease severity. Improvements in oxygenation were partly due to lung recruitment. Prone positioning should be considered in patients with SARS-CoV-2 ARDS.

Improved diagnosis of SARS-CoV-2 by using nucleoprotein and spike protein fragment 2 in quantitative dual ELISA tests.

The novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative enzyme-linked immunosorbent assays (ELISAs) that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive coronavirus disease-2019 (COVID-19) cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients who had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.