Deceiving SARS-CoV-2 molecular-tropism clues - A combinational contemporary strategy.

Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 frompreponetargets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificialsurfactantsystem as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery. Overall we postulate focused insights by employing a combinational contemporary strategy to steer towards a prospective direction on combating SARS-CoV-2.

Video-based reflection on neonatal interventions during COVID-19 using eye-tracking glasses: an observational study.

OBJECTIVE: The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic. DESIGN: Observational prospective single-centre study. SETTING: Neonatal intensive care unit at the Leiden University Medical Center. PARTICIPANTS: All local neonatal healthcare providers. INTERVENTION: There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection. RESULTS: We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9±3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19. CONCLUSION: We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.

Nanoparticle-mediated surfactant therapy in patients with severe COVID-19: a perspective.

Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.

Beneficial effects of inhaled surfactant in patients with COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: We have investigated the use of nebulized surfactant as a potential therapeutic option for the patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) undergoing non-invasive ventilation. METHODS: The patients were divided into 2 groups: surfactant (n = 33) and control (n = 32). The subjects in the surfactant group received the inhaled surfactant at daily dose of 150-300 mg. The oxygenation parameters and several clinical outcomes were analyzed. RESULTS: On the 5 day of therapy, PaO2/FiO2 improved significantly in the surfactant group compared to the control group (184 (155-212) mmHg vs 150 (91-173) mmHg, p = 0.02). The inhaled surfactant significantly reduced the need for transfer of patients to intensive care units (24.2% vs 46.9%, p = 0.05) and invasive mechanical ventilation (18.2% vs 40.6%, p = 0.04). Even more, the nebulized surfactant shortened the length of non-invasive ventilation (7 (3-13) days vs 11 (5-22) days, p = 0.02) and time spent in hospital (18 (16-27) days vs 26 (21-31) days, p = 0.003) in patients suffering from COVID-19-linked ARDS. CONCLUSIONS: Our preliminary data provided indications that inhaled surfactant therapy may represent a promising option for patients with COVID-19-associated ARDS. However, larger clinical trials are crucially needed.

Surfactant for the Treatment of ARDS in a Patient With COVID-19.

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.

Proposal of selective wedge instillation of pulmonary surfactant for COVID-19 pneumonia based on computational fluid dynamics simulation.

BACKGROUND: The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. PS instillation therapy is dramatically effective for infant respiratory distress syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that this ineffectiveness of PS instillation for ARDS is caused by insufficient delivery. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions. METHODS: Two types of 3D human airway models were prepared: one was from the trachea to the lobular bronchi and the other was from a subsegmental bronchus to respiratory bronchioles. The thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. The liquid layer was assumed to be replaced by an instilled PS. The flow rate of the instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving the advective-diffusion equation. RESULTS: The driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure was given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS does not reach the alveolar regions but moves to and fro within the airway according to the change in ventilator pressure. The driving pressure from subsegmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation. CONCLUSIONS: The simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia before the onset of ARDS. It will be also useful for preventing secondary lung fibrosis.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

The effect of surfactant on clinical outcome of patients with COVID-19 under mechanical ventilation: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Assessing the effect of surfactant on clinical outcome in patients with COVID-19 under mechanical ventilation TRIAL DESIGN: Single centre, two arm, parallel group (1:1 allocation ratio), randomised superiority trial with blinded care and outcome assessment. PARTICIPANTS: Inclusion criteria: Adult COVID-19 patients admitted to the ICU in Modarres hospital, Tehran, Iran (age range of 18 to 99 years) with moderate to severe ARDS (based on definition of P/F ratio) requiring auxiliary respiratory devices (either intubation or face mask). EXCLUSION CRITERIA: ● Existence of a major underlying pulmonary disease in addition to COVID-19 ● Underlying congenital heart disease ● Patients needing extracorporeal membrane oxygenation (ECMO) ● ARDS primarily due to any other reason rather than COVID-19 ● The primary source of pulmonary involvement was bacterial pneumonia or any other etiology except for COVID-10 induced lung involvement ● Those who refused to continue the study (either the patient or their family) ● any patient had any sign of healing before entering the study leading to discharge from ICU in less than 12 hours INTERVENTION AND COMPARATOR: In the intervention group, the dose of the drug is a vial containing 4 ml, equivalent to 100 mg, which is prescribed for an adult weighing about 70 kg each time, and if the patient's weight is much lower or higher, it will be adjusted accordingly. Surfactant is prescribed inside the trachea in two doses, starting on the day of intubation with a second dose 6 hours later. The control group will receive the same volume of normal saline, based on weight, administered into the trachea with the same time schedule. MAIN OUTCOMES: 30 days mortality; patient mortality during stay in ICU up to 30 days; ICU length of stay up to 30 days; Time under mechanical ventilation up to 30 days. RANDOMISATION: After the participant enters the study, i.e. after the qualification of the patients in the trial is confirmed and their informed written consent is taken, we will use a simple randomisation method using a table of random numbers. In order to hide the random allocation process, a central randomisation approach will be used and the random sequence will be at the disposal of one of the researchers, excluding the principal investigator. BLINDING (MASKING): Participants, healthcare providers and the principal investigator assessing the outcomes will all be blinded to the group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 60 participants will be randomised in a 1:1 allocation ratio (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: IRCT registration number: IRCT20091201002804N12 Registration date: 1st June 2020, 1399/03/12 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.