A Unique Case of Acute Respiratory Distress Syndrome Secondary to Rheumatoid Lung Disease With Administration of Anti-Tumor Necrosis Factor Alpha (TNFα) Agent.

Patients with rheumatoid arthritis (RA) may experience complications directly from the disease process or from immune-modulating agents used to treat RA. Adalimumab is a recombinant human monoclonal antibody directed against tumor necrosis factor alpha (TNFα) which has been increasingly used in the management of inflammatory and autoimmune diseases. Acute lung injury has been associated with the use of anti-TNFα agents, but the association with adalimumab is rare. Here we present a case of a patient with RA-associated lung disease who developed acute respiratory distress syndrome while being treated with adalimumab. Adalimumab-related lung injury is less common than lung injury associated with other anti-TNFα drugs, thus clinicians should be aware of this condition, as prompt recognition and supportive management can help prevent worsening outcomes.

Efficacy and safety of thrombolysis in COVID19 related ARDS.

INTRODUCTION: COVID19 causes significant pulmonary microthrombi in some individuals, which can lead to ARDS and death. Thrombolysis could be an effective approach in some patients with severe ARDS. We describe our experience with usage of thrombolytic agents in COVID19 critically ill patients, who were in worsening respiratory failure. METHODOLOGY: Retrospective chart analysis was done in patients who were thrombolysed between May 2020- Sept 2020. Analysis was done to find out factors associated with improvement in oxygenation and survival. RESULTS: Twenty seven patients with severe ARDS [all had respiratory rate >30, FiO2 >0.6(on NIV/HFNC) and PiO2/FiO2 ratio<120] were thrombolysed in our ICU for COVID19 causes. C.T. Pulmonary Angiography could not be done in any of the 27 patients due to poor general condition, but 2D echo was normal in most (5 had dilated RA,RV) and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation (defined by decrease in FiO2 by ≥0.2) in twenty patients. Five patients had major bleed. Eleven patients survived (survival rate of 40.7%) and survival rate was high { 66% (8/12)} in patients who were thrombolysed within 2 days of oxygen requirement. CONCLUSION: In this unprecedented pandemic with high mortality rates, efficacy of early thrombolysis needs to be further explored in randomised controlled trials.

Current status and prospect of global development of lung transplantation

During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.Copyright © 2022 Organ Transplantation. All rights reserved.

Mechanical Ventilation in ARDS

Acute respiratory distress syndrome (ARDS) is a form of hypoxemic respiratory failure, which requires supplemental oxygen delivered by mechanical ventilation, either noninvasively or more commonly by invasive mechanical ventilation. Although not currently meeting the definition for ARDS, these patients may also use heated high-flow nasal cannula and can sometimes avoid invasive mechanical ventilation as a result. The avoidance of worsening acute lung injury using lung-protective ventilation is the first principle of invasive mechanical ventilation in these patients. Conventionally, this involves keeping the plateau pressure below 30 cm H2O by using low tidal volume ventilation, based on ideal body weight. Multiple observational series suggest that targeting a low driving pressure concurrently is also important. The determination of the optimal setting for positive end-expiratory pressure (PEEP) remains controversial. The mode of ventilation utilized may be either volume or pressure limited. It has been suggested that vigorous respiratory efforts can worsen lung injury and are best avoided whenever possible. Modes of ventilation such as airway pressure release ventilation lack evidence to support use and should not be used. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Development and prospect of clinical research on lung transplantation in post-COVID-19 era

Lung transplantation has been advanced for nearly half a century around the globe, and it has been developed rapidly for over 20 years in China. The field of lung transplantation in China has been gradually integrated into the international community. The outbreak of novel coronavirus pneumonia (COVID-19) in 2020 brought big challenges, as well as diverted the worldwide attention to the development of lung transplantation in China, accelerating international communication and cooperation. With the steadily deepening of clinical and basic research on lung transplantation for severe cases of COVID-19, organ transplant physicians have deepened the understanding and thinking of the maintenance of donors, selection of elderly and pediatric candidates, and perioperative management of recipients, as the future perspective of lung transplantation in China. For interdisciplinary research related to lung transplantation, it is necessary to carry out multi-center clinical trials with qualified study design and constantly promote the theoretic and practical innovation.Copyright © 2021 The authors.

Invasive Mechanical Ventilation in COVID-19

Patients with severe COVID-19 pneumonia present with severe hypoxemic respiratory failure, typically meet the clinical criteria for acute respiratory distress syndrome (ARDS) and often require invasive mechanical ventilation. While peculiar pathophysiological aspects deserve discussion to better tailor the mechanical ventilation settings in these patients, most recommendations on the ventilatory management of these patients are derived from studies in patients with ARDS from causes other than COVID-19. Protective ventilation is recommended in most COVID-19 patients, tidal volume should be kept around 6 mL per kg of predicted body weight, positive end-expiratory pressure (PEEP) should be titrated individually considering that in many patients with COVID-19 improvement of oxygenation at higher PEEP is often accompanied by worsening of respiratory system compliance. Therefore, attention should be paid in limiting plateau and driving pressures to avoid excessive strain potentially resulting in ventilator-induced lung injury. Prone positioning has been used extensively in COVID-19 patients, but its impact on mortality is uncertain. Inhaled nitric oxide, extracorporeal CO2 removal (ECCO2R), and extracorporeal membrane oxygenation (ECMO) should be considered in selected patients as rescue measures. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Lack of a prompt normalization of immunological parameters is associated with long-term care and poor prognosis in COVID-19 affected patients receiving convalescent plasma: a single center experience.

OBJECTIVES: Being COVID-19 convalescent plasma (CCP) a therapeutic option that can have a potential impact on the normalization of immunological parameters of COVID-19 affected patients, a detailed analysis of post-infusion immunological changes was conducted in CCP treated patients, aiming to identify possible predictive hallmarks of disease prognosis. METHODS: This prospective observational study describes a cohort of 28 patients who received CCP shortly after being hospitalized for COVID-19 and diagnosed for Acute Respiratory Distress Syndrome. All patients were subjected to a detailed flow cytometry based evaluation of immunological markers at baseline and on days +3 and +7 after transfusion. RESULTS: At baseline almost all patients suffered from lymphopenia (25/28 on T-cells and 16/28 on B-cells) coupled with neutrophil-lymphocyte ratio exceeding normal values (26/28). Lymphocyte subsets were generally characterized by increased percentages of CD19+CD20-CD38hiCD27+ plasmablasts and reduction of CD4+CD45RA+CCR7+CD31+ recent thymic emigrants, while monocytes presented a limited expression of CD4 and HLA-DR molecules. Amelioration of immunological parameters began to be evident from day +3 and became more significant at day +7 post-CCP transfusion in 18 patients who recovered within 30 days from hospitalization. Conversely, baseline immunological characteristics generally persisted in ten critical patients who eventually progressed to death (6) or long-term care (4). CONCLUSIONS: This study demonstrates that proper immunophenotyping panels can be potentially useful for monitoring CCP treated patients from the first days after infusion in order to presume higher risk of medical complications.

Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1.

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

Ventilatory support in Covid-19 pneumonia.

The Covid-19 pandemic led to a major influx of patients suffering from acute hypoxemic respiratory failure, which conducted intensivists to adapt ICU structures and question respiratory support strategies. Available data suggest that pathophysiology of Covid-19 associated - acute respiratory distress syndrome (ARDS) is substantially similar to the pathophysiology of ARDS unrelated to Covid-19. Specific vascular injuries may however be more frequent during Covid-19 and some patients may present a major alteration in hypoxic pulmonary vasoconstriction. To date, ventilatory support strategies of patients with Covid-19 should be in line with guidelines for ARDS unrelated to Covid-19, including in particular a cautious evaluation of positive end-expiratory pressure effects.Copyright © SRLF 2021.

A Review on Catastrophic Evolution of SARS-CoV to SARS-CoV2: A Global Pandemic

The coronaviruses, belonging to the family Coronaviridae, have caused a massive pandemic in December 2019 after their previous outbreaks as SARS-CoV and MERS. The outbreak is believed to have originated from the seafood and live market in the Hubei province of China. The Rhinolophus species are the natural hosts of this virus. This virus caused pneumonia and took away many lives be-fore it was recognized as the novel Coronavirus. Very little information is available about the biology and nature of the novel Coronavirus. This article reviews multiple aspects encompassing its origin, epi-demiology, pathogenesis, symptoms, and the global statistics of spread. Acute respiratory distress syndrome (ARDS) is the key symptom of this condition. Angiotensin-converting enzyme 2 (ACE2) helps in the penetration of the virus into the target cells. Deeper research and understanding are essential for the identification of antibodies that inhibit ACE2 and can prevent viral replication. Drug design and control of disease are crucial. In countries like India, where plant diversity is extensive, it is prudent to focus on plant-based alternative drugs. Many attempts have been made to review and curate the drug discovery attempts using immuno-informatic and bioinformatic tools.Copyright © 2021 Bentham Science Publishers.

Guselkumab-Associated Pulmonary Disease and Diffuse Alveolar Hemorrhage with Drug Rash with Eosinophilia and Systemic Symptoms.

Psoriasis is a common skin condition worldwide. Moderate-to-severe disease is treated with biologic or non-biologic disease-modifying anti-rheumatic drugs. These include tumor necrosis factor (TNF)-a inhibitors, interleukin (IL)-17 inhibitors, and IL-23 inhibitors. Case reports of inhibitors of TNF-a and IL-12p40 subunits causing interstitial pneumonia (IP) have been published in the literature, but no case of anti-IL-23p19 subunit biologics causing IP and acute respiratory distress syndrome (ARDS) has been reported before. We report a case of a patient with restrictive lung disease secondary to a body mass index of 36.54 kg/m2, obstructive sleep apnea, and psoriasis, who developed IP and ARDS presumed to be secondary to guselkumab, an anti-IL-23p19 subunit monoclonal antibody. He was on ustekinumab, an anti-IL-12/23p40 for the treatment of psoriasis, but was switched to guselkumab eight months before the presentation, and since then he had been complaining of progressive shortness of breath. He initially presented to the hospital after having drug reaction with eosinophilia and systemic symptoms (DRESS) after being started on amoxicillin for a tooth infection. He was treated with high-dose intravenous steroids but developed progressive shortness of breath. Broad-spectrum antibiotics were added. An extensive infectious, autoimmune, and hypersensitivity work-up was undertaken, which returned negative. A bronchoscopy with bronchoalveolar lavage was performed, which revealed diffuse alveolar hemorrhage (DAH). His lung imaging and oxygenation progressively got worse; hence, no lung biopsy was taken. He was intubated and required inhaled nitric oxide, but due to the lack of improvement, the family elected for comfort measures, and the patient was extubated and passed away. To our knowledge, this is the first case of an association between guselkumab, IP, ARDS, and DAH. Rare instances of DAH with DRESS have been reported before. Whether it was DRESS or guselkumab that caused DAH was uncertain in our patient. Clinicians should monitor for DAH and shortness of breath in patients on guselkumab so that more data can be obtained and studied in the future.

Insights into COVID-19-associated critical illness: a narrative review.

Background and Objective: Since the outbreak of the 2019 novel coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) and sepsis resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have surged in intensive care units around the world. The heterogeneity of ARDS and sepsis has long been observed, and multiple subphenotypes and endotypes correlated with different outcomes and treatment response have been identified in the search for treatable traits. Despite their similarity to typical ARDS and sepsis, COVID-19-associated ARDS and sepsis harbor distinct features, raising the question as to whether they could be considered as subphenotypes or endotypes of the historical syndromes and, accordingly, benefit from specific therapeutic strategies. This review aimed to summarize and discuss the current knowledge of COVID-19-associated critical illness and the intrinsic subphenotypes or endotypes. Methods: Literature on the pathogenesis of COVID-19 and the subphenotyping of COVID-19-associated critical illness was derived from the PubMed database and reviewed. Key Content and Findings: Accumulating evidence, varying from clinical observation to basic research, has contributed to revealing the fundamental pathophysiological features of severe COVID-19 and has advanced our knowledge of the disease. COVID-19-associated ARDS and sepsis exhibit some distinctive features compared to the classic syndromes, including remarkable vascular abnormality and coagulopathy, and distinct respiratory mechanics and immune response. Some conventional subphenotypes derived from classic ARDS and sepsis have been validated in COVID-19, while novel subphenotypes and endotypes have also been identified in patients with this disease, who experience variable clinical outcomes and treatment responses. Conclusions: Subphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.

Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). METHODS: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. RESULTS: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = -0.35 (-0.6-0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. CONCLUSIONS: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury.

Management of hypoxemia in SARS-CoV-2 infection: Lessons learned from one year of experience, with a special focus on silent hypoxemia.

Silent hypoxemia is common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this article, the possible pathophysiological mechanisms underlying respiratory symptoms have been reviewed, and the presence of hypoxemia without hypoxia is also discussed. The experience we have gained since the start of the Coronavirus disease 19 (COVID-19) pandemic has changed our point of view about which patients with respiratory involvement should be admitted to the intensive care unit/high-dependency unit for mechanical ventilation and monitoring. In patients with clinically well-tolerated mild to moderate hypoxemia (silent hypoxemia), regardless of the extent of pulmonary opacities found in radiological studies, the administration of supplemental oxygen therapy may increase the risk of endothelial damage. The risk of sudden respiratory arrest during emergency intubation, which could expose healthcare workers to infection, should be considered along with the risks of premature intubation. Criteria for intubation need to be revisited based on updated evidence showing that many patients with severe hypoxemia do not show increased work of breathing. This has implications in patient management and may explain in part reports of broad differences in outcomes among intubated patients.

The Impact of Granulocyte Colony-Stimulating Factor Administration in a Neutropenic Cancer Patient With COVID-19-Related Acute Respiratory Distress Syndrome.

Chemotherapy-induced neutropenia is a serious adverse effect found in cancer patients treated with chemotherapy. As these patients are at risk of infections, granulocyte colony-stimulating factors (G-CSF) are commonly used in these patients to increase neutrophil counts. This report describes a case of a 73-year-old female with metastatic breast cancer treated with letrozole and palbociclib who presented to the hospital with flu-like symptoms and a positive SARS-CoV-2 test. She was saturating well on room air without the need for supplemental oxygen initially, however, she was febrile and lab work revealed neutropenia. Subsequently, she was given two doses of Tbo-filgrastim. Her respiratory status deteriorated shortly afterward and she required supplemental oxygen. The chest X-ray obtained at that time revealed increased atelectasis or infiltration in the middle and lower lung fields, and computed tomography angiography of the chest revealed bilateral patchy airspace and ground glass opacities. The timeline from symptom onset along with her imaging findings suggested COVID-19-related acute respiratory distress syndrome (ARDS) as a possible explanation for her respiratory status decline. Interestingly, her neutrophil-to-lymphocyte ratio (NLR) had consistently increased, along with her respiratory status deterioration, after the completion of the two doses of G-CSF. The patient was treated with dexamethasone. Her respiratory status eventually improved prior to discharge.

Assessment of respiratory support decision and the outcome of invasive mechanical ventilation in severe COVID-19 with ARDS.

Background: The coronavirus disease 2019 (COVID-19) is an ongoing pandemic. Invasive mechanical ventilation (IMV) is essential for the management of COVID-19 with acute respiratory distress syndrome (ARDS). We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV. Methods: In this retrospective, single-center, case series study, patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University, China, from January 8th, 2020, to March 24th, 2020, with the final follow-up date of April 20th, 2020, were included. Demographic, clinical, laboratory, imaging, and management information were collected and analyzed. Compliance with the respiratory support decision system was documented, and its relationship with 28-day mortality was evaluated. Results: The study included 46 COVID-19-associated ARDS patients who required IMV. The median age of the 46 patients was 68.5 years, and 31 were men. The partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at intensive care unit (ICU) admission was 104 mmHg. The median total length of IMV was 12.0 (interquartile range [IQR]: 6.0-27.3) days, and the median respiratory support decision score was 11.0 (IQR: 7.8-16.0). To 28 days after ICU admission, 18 (39.1%) patients died. Survivors had a significantly higher respiratory support decision score than non-survivors (15.0 [10.3-17.0] vs. 8.5 (6.0-10.3), P = 0.001). Using receiver operating characteristic (ROC) curve to assess the discrimination of respiratory support decision score to 28-day mortality, the area under the curve (AUC) was 0.796 (95% confidence interval [CI]: 0.657-0.934, P = 0.001) and the cut-off was 11.5 (sensitivity = 0.679, specificity = 0.889). Patients with a higher score (>11.5) were more likely to survive at 28 days after ICU admission (log-rank test, P < 0.001). Conclusions: For severe COVID-19-associated ARDS with IMV, following the respiratory support decision and assessing completion would improve the progress of ventilation. With a decision score of >11.5, the mortality at 28 days after ICU admission showed an obvious decrease.

Factors Affecting Confirmed COVID-19 Patient's Recovery Time at King Abdulaziz Medical City, Jeddah.

INTRODUCTION: The COVID-19 pandemic has become a threat to the public's health, especially to the elderly and those with chronic conditions. It is capable of spreading from carriers who are both asymptomatic and symptomatic. Associated factors such as age, sex, severe symptoms of COVID-19 disease, and chronic disease have a significant impact on the recovery time of patients. AIM: The study aimed to determine associated factors on recovery time in COVID-19 patients hospitalized at King Abdulaziz Medical city. METHODS: A single-center retrospective study was utilized to recruit 1776 confirmed COVID-19 patients from 13 September to 24 October 2020 at King Abdulaziz Medical City (KAMC) in Jeddah. RESULTS: The patients were categorized into three age groups: below 5 years, 5 to 65 years, and above 65 years. The number of male patients in each group was 49, 764, and 73, and the number of female patients in each group was 54, 754, and 82, respectively. Impact recovery time on female patients was 11.75 days; with male patients was 10.95 days. Symptoms such as sore throat, diarrhea, and fever in female patients declined the recovery time. On the other hand, symptoms such as runny nose, diarrhea, fever, and headache in male patients declined the recovery time. DISCUSSION AND CONCLUSION: It was revealed that older aged COVID-19 patients, male sex, and some symptoms decline recovery time. The study findings show an independent predictor of particular symptoms and sign which delay the time of recovery in the COVID-19 patients enrolled in the study differently, for male and female patients. Thus, patients who are infected with COVID-19 should be monitored keenly to prevent a prolonged rate of recovery and should be eligible for priority management to enhance a good clinical outcome.

Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.

Clinical studies have shown a significant positive correlation between age and the likelihood of being infected with SARS-CoV-2. This increased susceptibility is positively correlated with chronic inflammation and compromised neurocognitive functions. Postmortem analyses suggest that acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), with systemic and lung hyperinflammation, can cause significant morbidity and mortality in COVID-19 patients. Supraphysiological supplemental oxygen, also known as hyperoxia, is commonly used to treat decreased blood oxygen saturation in COVID-19 patients. However, prolonged exposure to hyperoxia alone can cause oxygen toxicity, due to an excessive increase in the levels of reactive oxygen species (ROS), which can overwhelm the cellular antioxidant capacity. Subsequently, this causes oxidative cellular damage and increased levels of aging biomarkers, such as telomere shortening and inflammaging. The oxidative stress in the lungs and brain can compromise innate immunity, resulting in an increased susceptibility to secondary lung infections, impaired neurocognitive functions, and dysregulated hyperinflammation, which can lead to ALI/ARDS, and even death. Studies indicate that lung inflammation is regulated by the central nervous system, notably, the cholinergic anti-inflammatory pathway (CAIP), which is innervated by the vagus nerve and α7 nicotinic acetylcholine receptors (α7nAChRs) on lung cells, particularly lung macrophages. The activation of α7nAChRs attenuates oxygen toxicity in the lungs and improves clinical outcomes by restoring hyperoxia-compromised innate immunity. Mechanistically, α7nAChR agonist (e.g., GAT 107 and GTS-21) can regulate redox signaling by 1) activating Nrf2, a master regulator of the antioxidant response and a cytoprotective defense system, which can decrease cellular damage caused by ROS and 2) inhibiting the activation of the NF-κB-mediated inflammatory response. Notably, GTS-21 has been shown to be safe and it improves neurocognitive functions in humans. Therefore, targeting the α7nAChR may represent a viable therapeutic approach for attenuating dysregulated hyperinflammation-mediated ARDS and sepsis in COVID-19 patients receiving prolonged oxygen therapy.

Effect Of Eight Hours Per Day Of Intermittent Self Prone Positioning For Seven Days On The Severity Of Covid-19 Pneumonia/ Acute Respiratory Distress Syndrome.

BACKGROUND: Prone positioning improves ventilation-perfusion mismatch, distribution of gravitational gradient in pleural pressure, and oxygen saturation significantly in patients with Covid pneumonia. We aimed to find out the efficacy of eight hours per day of intermittent selfprone positioning for seven days in patients affected with COVID-19 pneumonia/ ARDS. METHODS: This Randomized Clinical Trial was conducted in the Covid isolation wards of Ayub Teaching Hospital, Abbottabad. Patients suffering from COVID-19 pneumonia/ ARDS were enrolled with permuted block randomization into a control and an experimental group each consisting of 36 patients. Parameters of Pneumonia Severity Index (PSI) score along with other sociodemographic data was noted on a preformed structured questionnaire. Death was confirmed by requesting the death certificate of patients on the 90th day of enrolment. Data Analysis was done with SPSS Version 25. Tests of significance were applied to calculate the difference in the patients of the two groups with respect to respiratory physiology and survival. RESULTS: The mean age of the patients was 63.79±15.26 years. A total of 25 (32.9%) male and 47 (61.8%) female patients were enrolled. Statistically significant improvement was found in the respiratory physiology of the patients at 7th and 14th DOA between the groups. Pearson Chi-Square test of significance showed a difference in mortality between the two groups at 14th DOA (pvalue=0.011) but not at 90th DOA (p-value=0.478). Log Rank (Mantel-Cox) test of significance, applied on the Kaplan Meier curve and showed no statistically significant difference among the groups based on the survival of the patients. (p-value=0.349). CONCLUSIONS: Early transient improvement in respiratory physiology and mortality does occur with 8 hours of self-prone positioning for seven days but there is no effect on the 90-day survival of the patients. Thus, the impact of the manoeuvre on improving survival needs to be explored with studies having an application of the manoeuvre for a longer duration and period.