Pathophysiology of thromboembolism in patients with COVID-19

Introduction and aim. A small number of critically ill patients with coronavirus disease (COVID-19) develop thromboembolism (arterial or venous), both micro- and macrovascular complications such as deep vein thrombosis, pulmonary embolism, and pulmonary arterial thrombosis. The objective of the study is to describe the pathophysiology of venous thromboembolism in patients with COVID-19. Material and methods. In this article a narrative review regarding pathophysiology of thromboembolism in patients with COVID-19. Analysis of the literature. The development of coagulopathy is a consequence of the intense inflammatory response associated with hypercoagulability, platelet activation, and endothelial dysfunction. The pathophysiology that relates pulmonary thromboembolism (PTE) with COVID-19 is associated with a hypercoagulable state. PTE is suspected in hospitalized patients presenting dyspnea, decreased oxygen requirement, hemodynamic instability, and dissociation between hemodynamic and respiratory changes. In COVID-19-associated coagulopathy, initially, patients present with elevated levels of fibrinogen and D-dimer, with minimal changes in prothrombin time and platelet count. The main risk factor for the development of pulmonary embolism is the increase in D-dimer that is associated with the development of PTE. The administration of iodine-based contrast agent to patients with COVID-19 would affect P-creatinine and renal function, where Ultrasound is viewed as cost-effective and highly portable, can be performed at the bedside. Conclusion. Acute respiratory distress syndrome severity in patients with COVID-19 can explain PTE as a consequence of an exaggerated immune response. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

Building Geographic Information System Story Maps for Jakarta's Local Community Health Infrastructures Awareness

COVID-19 is caused by the novel coronavirus SARS-CoV-2. First started in Wuhan, COVID-19 has spread everywhere, including Indonesia. COVID-19 can cause severe pneumonia, severe acute respiratory distress syndrome (ARDS) symptoms, and multiple organ failure. According to the WHO, COVID-19 generally has an incubation period of 5-6 days, ranging from 1 to 14 days. However, in Jakarta, the cases have decreased significantly since the implementation of PPKM (Restrictions of Activity), running since early July 2021. The government claimed that the PPKM rule has significantly impacted COVID-19 cases, decreasing every day, especially in Jawa-Bali Region. In addition, the Vaccination rate in Indonesia also played a significant part in decreasing COVID-19 cases, with Jakarta currently standing with 9 million people fully vaccinated per December 2021. To monitor the development of COVID-19 in Jakarta and provide information to the public about health facilities, especially hospitals in Jakarta, in this study, the distribution area of COVID-19 cases will be mapped with CHIME using ArcGIS Online tools. The analysis results obtained based on the mapping results that most cases were in the Cengkareng area, and the area with the most hospitals werein East Jakarta. © 2022 IEEE.

THE POSSIBILITY OF USING PERFLUOROCARBON COMPOUNDS FOR VIRUS-ASSOCIATED PNEUMONIA TREATMENT

The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed — gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last–the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

Tocilizumab Initiation based on Indicator in Patients Infected by Coronavirus-19 to Prevent Intubation

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created severe medical and economic consequences worldwide since 2019. Tocilizumab is one of the therapies considered capable of improving the condition of patients with COVID-19. However, there is not much information about the best time to give tocilizumab. METHOD(S): This was an analytical study with a retrospective cohort design, using the data of 125 patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with signs of acute respiratory distress syndrome in Dr. Moewardi Hospital, Surakarta, from March to August 2020. We analyzed various available clinical data to see which factors into clinical improvement with tocilizumab therapy. RESULT(S): Most patients showed clinical improvement after administration of tocilizumab. During the follow-up period, 21 patients died despite tocilizumab therapy. Significant risk factors associated with the need for intubation were heart rate, neutrophil, lymphocyte, pH, PaCO2, and PO2. The most influential variable on the need for intubation without being associated with other risk factors was PaO2 (p = 0.003, Confidence Intervals 95%). CONCLUSION(S): Tocilizumab has a role in treating patients infected by SARS-CoV-2, preventing the need for intubation when given to patients in good saturation condition with oxygen supplementation without positive pressure (PaO2 >65mmHg;SpO2 >93%).Copyright © 2023 Septian Adi Permana, Adhrie Sugiarto, Sidharta Kusuma Manggala, Muhammad Husni Thamrin, Purwoko Purwoko, Handayu Ganitafuri.

Research progress of ulinastatin in treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is still spreading worldwide. At present, no specific drug has been developed for the virus. Ulinastatin plays an important role in anti-inflammatory. Clinically, it is mainly used in acute pancreatitis, shock and disseminated intravascular coagulation. It also has the effects of antioxidant stress, anticoagulation and immune regulation, which may be of great significance to reduce the severity and mortality of COVID-19. Combined with the pharmacological effect of ulinastatin and its clinical application in the treatment of COVID-19 complications such as acute respiratory distress syndrome and sepsis lung injury, this paper discusses the feasibility of its application in COVID-19, so as to provide help for the clinical treatment and new drug research and development of this disease.Copyright © 2022 Tianjin Press of Chinese Herbal Medicines. All Rights Reserved.

Severe coronavirus disease 2019: Is it acute respiratory distress syndrome?.

The outbreak of coronavirus disease 2019 (COVID-19) poses a major global threat. Although we have learned a lot about COVID-19 from clinical studies and autopsy findings, there is still a lot of confusion. One of the biggest controversies is whether severe COVID-19 can be diagnosed as acute respiratory distress syndrome (ARDS). Severe COVID-19 may meet ARDS Berlin criteria, but it differs from ARDS caused by other etiologies and is characterized by later onset time, relatively normal lung compliance in some cases, significant hypercapnia, lung CT findings, and significant coagulation activation in lungs. Some reports classify COVID-19-related ARDS into different phenotypes, but most of them are based on observational studies, with high bias. To date, we have not fully understood the pathophysiology of COVID-19-related ARDS. Premature phenotyping may mislead mechanical ventilation strategies. We expect evidence from large clinical studies.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Non-invasive respiratory support in patients with severe community-acquired pneumonia.

Acute respiratory failure (ARF) is the leading cause of death in hospitalized patients with severe forms of COVID-19. At the beginning of COVID-19 pandemic the starting respiratory protocol suggested early use of intubation and artificial lung ventilation (ALV) in patients with severe pneumonia complicated by ARF. However, after the analysis of the published studies it was noted that the pathophysiology of the development of ARF in COVID-19 had features that determine the atypical clinical pattern - "silent hypoxemia". This leads to the late onset of respiratory support (RS) and, as a result, to the lower effectiveness of non-invasive RS methods. This article discusses the creation of an algorithm for the early use of various non-invasive RS methods in patients with COVID-19 complicated by ARF, that will decrease the frequency of hospitalization to the Intensive care units, tracheal intubation and ALV, reduce the duration of treatment and improve prognosis.Copyright © 2023 IRBIS LLC. All Rights Reserved.

Surviving Sepsis Campaign COVID-19 Panel

In late 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2, led to an epidemic of acute respiratory syndrome and subsequently to a pandemic. The Surviving Sepsis Campaign COVID-19 expert group developed 54 urgent statements on the management of COVID-19 in the intensive care unit, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. The authors did not undertake a new systematic prioritization of results but used the current work of the Surviving Sepsis Campaign Guideline 2020 and expert opinion. The Surviving Sepsis Campaign COVID-19 Panel is divided into 4 groups: 1) infection control and testing: identification of aerosol-generating proce-dures, healthcare workers perform aerosol-generating procedures in a negative pressure room, using appropriate respiratory masks (N95 respirators, FFP2) and protective equipment (gloves, gown, eye protection, etc.);2) laboratory monitoring and specimens: each patient admitted to the intensive care unit with signs of respiratory infection should be considered as potentially infected with severe acute respiratory syndrome, and samples from the lower airways should be obtained after intubation and ventilation for diagnostic testing;3) hemodynamic support;4) respiratory support. The Grading of Recommendations, Assessment, Deve-lopment approach was used to assess the quality of evidence. The quality of evidence was assessed as high, moderate, low and very low. Online software was used — GDT (http://gdt.guidelinede-velopment.org) to generate the evidence profiles. © 2022, Zaslavsky Publishing House. All rights reserved.

Clinical and histo-pathophysiological features of diffused alveolar lesions (pneumonia) caused by SARS-CoV-2 in patients who need of respiratory support

Acute respiratory distress syndrome (ARDS) and respiratory failure are the main problems in patients with COVID-19. The main reason is primarily a violation of lung perfusion. Anatomical prerequisites for the work of PЕЕР (non-cardiogenic pulmonary edema, atelectasis and, consequently, the possibility of recruitment) are absent. Non-invasive lung ventilation can eliminate hypoxemia and reduce inspiratory effort. Otherwise, the use of mechanical ventilation to prevent self-induced lung injury should be considered. These characteristics are associated with a marked violation of the mechanics of respiration, high blood pressure of arterial carbon dioxide. The leading characteristic of COVID-19 progression is the gradual transition from edema or atelectasis to less reversible structural changes in the lungs, namely fibrosis. The mechanics of respiration are disturbed, the pressure of carbon dioxide in the arterial blood increases, the ability of the respiratory muscles decreases and there is no reaction to PЕEP in the abdominal position. © 2022. The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, CC BY, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.

Post COVID-19 Infection with Staphylococcus Aureus Bacteraemia: A Case Series

Staphylococcus aureus (S.aureus) is a leading bacterial pathogen, that causes deadly infections such as bacteraemia, Toxic Shock Syndrome (TSS) and endocarditis. It has been the main contributor to secondary bacterial infections during viral pandemics, greatly raising patient morbidity and fatality rates. It is unknown how this secondary bacteraemia would affect people who have Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV2). Herein, the authors present a series of case studies of 8 patients, (4 males and 4 females) infected with Coronavirus Disease-2019 (COVID-19) at tertiary hospital, Hyderabad, India, who eventually developed S.aureus bacteraemia with widespread seeding of secondary infections including cellulitis and abscess formation. Adult patients aged 20-60 years of age who were infected with COVID-19 from June'2022-August'2022 and had positive bacterial cultures for S.aureus during admission were included in the study. A total of eight patients hospitalised for COVID-19 with secondary bacteraemia were identified. Of these patients admitted with severe limb infections, three patients expired after a week of ongoing treatment from their blood cultures. Multivariate analysis identified the onset of bacteraemia (>4 days from date of admission) and age as significant predictors of mortality in admitted patients. Systemic Inflammatory Response Syndrome (SIRS) scoring and blood cultures were used to identify the mortality risk with p-value=0.05 statistical significance. The patients were subsequently treated with antibiotics and given conservative management, some of the patients admitted to Intensive Care Unit (ICU) who had critical co-morbidities, expired within a week of ongoing treatment. The final outcome of the present case series was that bacteraemia caused by S.aureus is associated with a high mortality rate in COVID-19 patients. More research is needed to understand the relationship between COVID-19 and secondary S.aureus bacteraemia. [ FROM AUTHOR] Copyright of Journal of Clinical & Diagnostic Research is the property of JCDR Research & Publications Private Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Assessment of serum neopterin levels in patients hospitalized with severe COVID-19

Background: COVID-19 has caused a considerable number of hospital admissions in China since December 2019. Many COVID-19 patients experience signs of acute respiratory distress syndrome, and some are even in danger of dying. Background: to measure the serum levels of D-dimer, Neutrophil-Lymphocyte count ratio (NLR), and neopterin in patients hospitalized with severe COVID-19 in Baghdad, Iraq. And to determine the cut-off values (critical values) of these markers for the distinction between the severe patients diagnosed with COVID-19 and the controls. Materials and methods: In this case-control study, we collect blood from 89 subjects, 45 were severe patients hospitalized in many Baghdad medical centers who were diagnosed with COVID-19 infection, and 44 were apparently healthy subjects as a control. The time of collection is from September 15 th to December 31 th, 2021. The optimal cut-off points (critical values) and prognostic relevance of D-dimer, Neutrophil-Lymphocyte count ratio (NLR), and neopterin were investigated using (ROC) curves analysis. Results: In severe patients hospitalized with COVID-19 the levels of D-dimer, NLR, and neopterin were statistically significantly higher than in control participants (P < 0.005). The D-dimer, NLR, and neopterin tests have areas under the receiver operating characteristic (ROC) curves of 0.920, 0.90, and 0.74 respectively, and their critical values for the differentiation between the severe patients and control were 0.22 micro g/ml, 2.56, and 3.02 nmol/L. Conclusions: D-dimer, NLR, and neopterin levels in sever COVID-19 patients were higher than control, with values of greater than 0.22 micro g/ml, 2.56 and 3.02 nmol/L respectively was linked to a severe COVID-19 infection with good sensitivity and selectivity.

Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib.

Background: Acute respiratory distress syndrome (ARDS) in corona virus disease 19 (COVID-19) is triggered by hyperinflammation, thus providing a rationale for immunosuppressive treatments. The Janus kinase inhibitor Ruxolitinib (Ruxo) has shown efficacy in severe and critical COVID-19. In this study, we hypothesized that Ruxo's mode of action in this condition is reflected by changes in the peripheral blood proteome. Methods: This study included 11 COVID-19 patients, who were treated at our center's Intensive Care Unit (ICU). All patients received standard-of-care treatment and n = 8 patients with ARDS received Ruxo in addition. Blood samples were collected before (day 0) and on days 1, 6, and 10 of Ruxo treatment or, respectively, ICU admission. Serum proteomes were analyzed by mass spectrometry (MS) and cytometric bead array. Results: Linear modeling of MS data yielded 27 significantly differentially regulated proteins on day 1, 69 on day 6 and 72 on day 10. Only five factors (IGLV10-54, PSMB1, PGLYRP1, APOA5, WARS1) were regulated both concordantly and significantly over time. Overrepresentation analysis revealed biological processes involving T-cells only on day 1, while a humoral immune response and complement activation were detected at day 6 and day 10. Pathway enrichment analysis identified the NRF2-pathway early under Ruxo treatment and Network map of SARS-CoV-2 signaling and Statin inhibition of cholesterol production at later time points. Conclusion: Our results indicate that the mechanism of action of Ruxo in COVID-19-ARDS can be related to both known effects of this drug as a modulator of T-cells and the SARS-CoV-2-infection.

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.

Exploring the learning needs of clinicians in Belgium and Sweden regarding prone positioning and skin damage prevention: A qualitative study.

INTRODUCTION: During the coronavirus pandemic (COVID -19), the use of prone positioning in critically ill patients with acute respiratory distress syndrome (ARDS) increased substantially. As a result, clinicians had to (re)learn how to treat the patient in the prone position while preventing adverse events such as pressure ulcers, skin tears and moisture-associated skin damage. AIM: The purpose of the study was to determine participants' learning needs related to patients in the prone position and the prevention of skin damage, such as pressure ulcers, and what they perceived as a positive or negative learning experience. DESIGN: This study used a qualitative methodological framework and employed an exploratory design. PARTICIPANTS: A purposive sample of clinicians (n = 20) with direct or indirect work experience with prone ventilated patients was recruited in Belgium and Sweden. METHODS: Individual semi-structured interviews were conducted in Belgium and Sweden between February and August 2022. Data were analysed thematically using an inductive approach. The COREQ guideline was utilised to comprehensively report on the study. FINDINGS: Two themes were identified: 'Adapting to a crisis' and 'How to learn', with the latter having two subthemes: 'balancing theory and practice' and 'co-creating knowledge'. Unexpected circumstances necessitated a personal adaption, a change in learning methods and a pragmatic adaptation of protocols, equipment and working procedures. Participants recognised a multifaceted educational approach which would contribute to a positive learning experience regarding prone positioning and skin damage prevention. The importance of poising theoretical teaching with practical hands-on training was highlighted with an emphasis on interaction, discussion, and networking between peers. CONCLUSIONS: The study findings highlight learning approaches which may help inform the development of befitting educational resources for clinicians. Prone therapy for ARDS patients is not limited to the pandemic. Therefore, educational efforts should continue to ensure patient safety in this important area.

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.

Prone positioning for mechanically ventilated patients with coronavirus disease 2019: the experience of an Irish regional hospital intensive care unit.

BACKGROUND: The benefits of prone positioning in acute respiratory distress syndrome (ARDS) have been known for many years. While some controversy exists regarding whether coronavirus disease 2019 (COVID-19) pneumonia should be treated with the same therapeutic strategies as for non-COVID ARDS, the Surviving Sepsis Campaign still provide a weak recommendation to utilise prone positioning in this setting. AIMS: The aims of this study are to ascertain if prone positioning improves oxygenation significantly in mechanically ventilated patients with severe COVID-19 ARDS and to describe the feasibility of frequent prone positioning in an Irish regional hospital intensive care unit (ICU) with limited prior experience. METHODS: In this retrospective, observational cohort study, we investigate if the PaO2/FiO2 ratio and ventilatory ratio improve during and following prone positioning, and whether this improvement correlates with patient baseline characteristics or survival. RESULTS: Between March 2020 and 2021, 12 patients underwent prone positioning while mechanically ventilated for severe COVID ARDS. Sixty-six percent were male, mean age 60.9 (± 10.5), mean BMI 33.5 (± 6.74) and median APACHE II score on admission to ICU was 10.5 (7.25-16.3). Further, 83% were proned within 24 h of being intubated due to refractory hypoxaemia. PaO2/FiO2 ratio improved from 11.6 kPa (9.80-13.8) to 15.80 kPa (13.1-19.6) while prone, p < 0.0001. CONCLUSIONS: We found prone positioning to be a safe method of significantly improving oxygenation in mechanically ventilated patients with severe COVID-19 ARDS. We did not find a relationship between patient baseline characteristics nor illness severity and degree of PaO2/FiO2 ratio improvement, nor did we find a relationship between degree of PaO2/FiO2 ratio improvement and survival.

Cannabinoids receptors in Covid-19: Perpetrators and victims.

COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the aim of the present narrative review was to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects with suppression of pro-inflammatory cytokines and inhibition of inflammatory signaling pathways.

Emerging role of long non-coding RNA MALAT1 related signaling pathways in the pathogenesis of lung disease.

Long non-coding RNAs (lncRNAs) are endogenously expressed RNAs longer than 200 nt that are not translated into proteins. In general, lncRNAs bind to mRNA, miRNA, DNA, and proteins and regulate gene expression at various cellular and molecular levels, including epigenetics, transcription, post-transcription, translation, and post-translation. LncRNAs play important roles in many biological processes, such as cell proliferation, apoptosis, cell metabolism, angiogenesis, migration, endothelial dysfunction, endothelial-mesenchymal transition, regulation of cell cycle, and cellular differentiation, and have become an important topic of study in genetic research in health and disease due to their close link with the development of various diseases. The exceptional stability, conservation, and abundance of lncRNAs in body fluids, have made them potential biomarkers for a wide range of diseases. LncRNA MALAT1 is one of the best-studied lncRNAs in the pathogenesis of various diseases, including cancers and cardiovascular diseases. A growing body of evidence suggests that aberrant expression of MALAT1 plays a key role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary diseases (COPD), Coronavirus Disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), lung cancers, and pulmonary hypertension through different mechanisms. Here we discuss the roles and molecular mechanisms of MALAT1 in the pathogenesis of these lung diseases.

Effectiveness of RCTs Pooling Evidence on Mesenchymal Stem Cell (MSC) Therapeutic Applications During COVID-19 Epidemic: A Systematic Review.

Background: Global pandemic identified as coronavirus disease 2019 (COVID-19) has resulted in a variety of clinical symptoms, from asymptomatic carriers to those with severe acute respiratory distress syndrome (SARS) and moderate upper respiratory tract symptoms (URTS). This systematic review aimed to determine effectiveness of stem cell (SC) applications among COVID-19 patients. Methods: Multiple databases of PubMed, EMBASE, Science Direct, Google Scholar, Scopus, Web of Science, and Cochrane Library were used. Studies were screened, chosen, and included in this systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flowchart diagram and PRISMA checklist. Included studies' quality was assessed employing Critical Appraisal Skills Programme (CASP) quality evaluation criteria for 14 randomized controlled trials (RCTs). Results: Fourteen RCTs were performed between the years of 2020 to 2022, respectively, with a sample size n = 574 (treatment group (n = 318); control group (n = 256)) in multiple countries of Indonesia, Iran, Brazil, Turkey, China, Florida, UK, and France. The greatest sample size reported from China among 100 COVID-19 patients, while the lowest sample of 9 COVID-19 patients from Jakarta, Indonesia, and the patient's age ranges from 18 to 69 years. Studies applied to the type of SC were "Umbilical cord MSCs, MSCs secretome, MSCs, Placenta-derived MSCs, Human immature dental pulp SC, DW-MSC infusion, Wharton Jelly-derived MSCs". The injected therapeutic dose was 1 × 106 cells/kg, 1 × 107 cells/kg, 1 × 105 cells/kg, and 1 million cells/kg as per the evidence from the different studies. Studies focused on demographic variables, clinical symptoms, laboratory tests, Comorbidities, respiratory measures, concomitant therapies, Sequential Organ Failure Assessment score, mechanical ventilation, body mass index, adverse events, inflammatory markers, and PaO2/FiO2 ratio were all recorded as study characteristics. Conclusion: Clinical evidence on MSC's therapeutic applications during COVID-19 pandemic has proven to be a promising therapy for COVID-19 patient recovery with no consequences and applied as a routine treatment for challenging ailments.