Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID-19) and the rationale for their utilization: A review. Giovane Richard A,Rezai Shadi,Cleland Ellen,Henderson Cassandra E Reviews in medical virology SARS-CoV-2 has caused a pandemic which is putting strain on the health-care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS-CoV-2 as there is no evidence to support therapies to improve outcomes in patients with SARS-CoV-2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS-CoV-2. To date, data is limited for medications that facilitate clinical improvement of COVID-19 infections. 10.1002/rmv.2136
    Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS). Dhawan Gaurav,Kapoor Rachna,Dhawan Rajiv,Singh Ravinder,Monga Bharat,Giordano James,Calabrese Edward J Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared a global public health emergency by WHO on Jan 30, 2020. Despite massive efforts from various governmental, health and medical organizations, the disease continues to spread globally with increasing fatality rates. Several experimental drugs have been approved by FDA with unknown efficacy and potential adverse effects. The exponentially spreading pandemic of COVID-19 deserves prime public health attention to evaluate yet unexplored arenas of management. We opine that one of these treatment options is low dose radiation therapy for severe and most critical cases. There is evidence in literature that low dose radiation induces an anti-inflammatory phenotype that can potentially afford therapeutic benefit against COVID-19-related complications that are associated with significant morbidity and mortality. Herein, we review the effects and putative mechanisms of low dose radiation that may be viable, useful and of value in counter-acting the acute inflammatory state induced by critical stage COVID-19. 10.1016/j.radonc.2020.05.002
    Predictive factors of mortality in patients treated with tocilizumab for acute respiratory distress syndrome related to coronavirus disease 2019 (COVID-19). Lohse Anne,Klopfenstein Timothée,Balblanc Jean-Charles,Royer Pierre-Yves,Bossert Marie,Gendrin Vincent,Charpentier Aline,Bozgan Ana-Maria,Badie Julio,Bourgoin Charlotte,Contreras Remy,Mazurier Isabelle,Conrozier Thierry,Zayet Souheil Microbes and infection COVID-19 patients (n = 34) suffering from ARDS were treated with tocilizumab (TCZ). Outcome was classified in two groups: "Death" and "Recovery". Predictive factors of mortality were studied. Mean age was 75.3, mean oxygen (O) requirements 10.4 l/min. At baseline, all patients had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer and liver enzymes). 24 patients (70.5%) recovered after TCZ therapy and 10 died (29.5%). Deceased subjects differed from patients in whom treatment was effective with regard to more pronounced lymphopenia (0.6 vs 1.0 G/l; p = 0.037), lower platelet number (156 vs 314 G/l; p = 0.0001), lower fibrinogen serum level (0.6 vs 1.0 G/l; p = 0.03), higher aspartate-amino-transferase (108 vs 57 UI/l; p = 0.05) and greater O requirements (11 vs 8 l/min; p = 0.003). 10.1016/j.micinf.2020.06.005
    Flow controlled ventilation in Acute Respiratory Distress Syndrome associated with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Roehrig Stefan,Ait Hssain Ali,Shallik Nabil Al Hamid,Elsaid Ingi Mohamed A,Mustafa Salma Faisal,Smain Osama A M,Molokhia Ashraf Abdulla,Lance Marcus D Trials OBJECTIVES:This study aims to demonstrate the positive effects on oxygenation of flow-controlled ventilation compared to conventionally ventilated patients in patients suffering from Acute respiratory distress syndrome (ARDS) associated with COVID-19.We define ARDS according to the "Berlin" definition integrating the oxygenation index (P/F ratio), the level of Positive End Expiratory Pressure (PEEP), radiological and clinical findings. TRIAL DESIGN:This is a prospective, randomized (1:1 ratio), parallel group feasibility study in adult patients with proven COVID-19 associated ARDS. PARTICIPANTS:All adult patients admitted to the ICU of Hamad Medical Corporation facilities in Qatar because of COVID-19 infection who develop moderate to severe ARDS are eligible. The inclusion criteria are above 18 years of age, proven COVID-19 infection, respiratory failure necessitating intubation and mechanical ventilation, ARDS with a P/F ratio of at least 200mmHg or less and a minimum PEEP 5cmH2O, BMI less 30 kg/ m2. The following exclusion criteria: no written consent, chronic respiratory disease, acute or chronic cardiovascular disease, pregnancy or need for special therapy (prone position and/or Extracorporeal membrane oxygenation). INTERVENTION AND COMPARATOR:After randomisation, the group A patients will be ventilated with the test-device for 48 hours. The settings will be started with the pre-existing-PEEP. The upper pressure will be determined to achieve a tidal volume of 6 ml/kg lean body mass, while the respiratory rate will be set to maintain an arterial pH above 7.2. In group B, the ventilator settings will be adjusted by the attending ICU team in accordance with lung-protective ventilation strategy. All other treatment will be unchanged and according to our local policies/guidelines. MAIN OUTCOMES:The primary end point is PaO2. As this is a dynamic parameter, we will record it every 6-8 hours and analyse it sequentially. RANDOMISATION:The study team screens the ventilated patients who fulfil the inclusion criteria and randomise using a 1:1 allocation ratio after consenting using a closed envelope method. The latter were prepared and sealed in advance by an independent person. BLINDING (MASKING):Due to the technical nature of the study (use of a specific ventilator) blinding is only possible for the data-analysts and the patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE):The sample size calculation based on the assumption of an effect size (change in PaO2) of 1.5 SDS in the primary endpoint (PaO2), an intended power of 80%, an alpha error of 5% and an equal sample ratio results in n=7 patients needed to treat. However, to compensate for dropouts we will include 10 patients in each group, which means in total 20 patients. TRIAL STATUS:The local registration number is MRC-05-018 with the protocol version number 3. The date of approval is 14 April 2020. Recruitment began 28th May 2020 and is expected to end in September 2020. TRIAL REGISTRATION:The protocol was registered before starting subject recruitment under the title: "Flow controlled ventilation in ARDS associated with COVID-19" in ClinicalTrials.org with the registration number: NCT04399317 . Registered on 22 May 2020. 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. 10.1186/s13063-020-04708-1
    A Comprehensive Review of Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome. Khiali Sajad,Khani Elnaz,Entezari-Maleki Taher Journal of clinical pharmacology Currently, the world is facing the pandemic of a novel strain of beta-coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS) is the most devastating complication of SARS-CoV-2. It was indicated that cytokine-release syndrome and dominantly interleukin (IL)-6 play a central role in the pathophysiology of ARDS related to the novel 2019 coronavirus disease (COVID-19). Despite the global emergency of the disease, at this time, there are no proven therapies for the management of the disease. Tocilizumab is a potential recombinant monoclonal antibody against IL-6 and currently is under investigation for the management of ARDS in patients with COVID-19. Given these points, we reviewed the current evidence regarding the potential therapeutic role of tocilizumab and its important clinical issues in the treatment of ARDS related to COVID-19. 10.1002/jcph.1693
    Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression. Mohammed Amira,F K Alghetaa Hasan,Miranda Kathryn,Wilson Kiesha,P Singh Narendra,Cai Guoshuai,Putluri Nagireddy,Nagarkatti Prakash,Nagarkatti Mitzi International journal of molecular sciences Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19. 10.3390/ijms21176244
    Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection-Associated Hemophagocytic Lymphohistiocytosis. Quan Chao,Li Caiyan,Ma Han,Li Yisha,Zhang Huali Clinical microbiology reviews The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection. 10.1128/CMR.00074-20
    The rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect. Can Alp,Coskun Hakan Stem cells translational medicine The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis with an extremely rapid progress resulting in thousands of patients who may develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) treatment. So far, no specific antiviral therapeutic agent has been demonstrated to be effective for COVID-19; therefore, the clinical management is largely supportive and depends on the patients' immune response leading to a cytokine storm followed by lung edema, dysfunction of air exchange, and ARDS, which could lead to multiorgan failure and death. Given that human mesenchymal stem cells (MSCs) from various tissue sources have revealed successful clinical outcomes in many immunocompromised disorders by inhibiting the overactivation of the immune system and promoting endogenous repair by improving the microenvironment, there is a growing demand for MSC infusions in patients with COVID-19-related ARDS in the ICU. In this review, we have documented the rationale and possible outcomes of compassionate use of MSCs, particularly in patients with SARS-CoV-2 infections, toward proving or disproving the efficacy of this approach in the near future. Many centers have registered and approved, and some already started, single-case or phase I/II trials primarily aiming to rescue their critical patients when no other therapeutic approach responds. On the other hand, it is also very important to mention that there is a good deal of concern about clinics offering unproven stem cell treatments for COVID-19. The reviewers and oversight bodies will be looking for a balanced but critical appraisal of current trials. 10.1002/sctm.20-0164
    Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology. Shelhamer Mehdi C,Wesson Paul D,Solari Ian L,Jensen Deanna L,Steele William Alex,Dimitrov Vihren G,Kelly John Daniel,Aziz Shazia,Gutierrez Victor Perez,Vittinghoff Eric,Chung Kevin K,Menon Vidya P,Ambris Herman A,Baxi Sanjiv M Journal of intensive care medicine BACKGROUND:Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS:A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS:Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 ( < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PO: FiO) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS:Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19. 10.1177/0885066620980399
    The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility. Bime Christian,Camp Sara M,Casanova Nancy,Oita Radu C,Ndukum Juliet,Lynn Heather,Garcia Joe G N Translational research : the journal of laboratory and clinical medicine Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into "personalized" medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies. 10.1016/j.trsl.2020.06.010
    High dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial. Maskin Luis Patricio,Olarte Gabriel Leonardo,Palizas Fernando,Velo Agostina E,Lurbet María Fernanda,Bonelli Ignacio,Baredes Natalio D,Rodríguez Pablo Oscar Trials OBJECTIVES:The aim of this study is to explore the effectiveness and safety of high dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to SARS-Cov-2 pneumonia. TRIAL DESIGN:Multicentre, randomized clinical trial, controlled, open label, parallel group, to evaluate the effectiveness and safety of high dose dexamethasone in adult patients with confirmed COVID-19, with Acute Respiratory Distress Syndrome. PARTICIPANTS:We will include patients with SARS-Cov-2 pneumonia who develop acute respiratory distress syndrome, in several intensive care units (ICU) in Buenos Aires, Argentina (CEMIC, Clinica Bazterrica, Sanatorio Sagrado Corazon) Inclusion criteria: Men and women, age ≥ 18 years old. Confirmed diagnosis of SARS-CoV-2 infection, by RT-PCR. Diagnosis of Acute Respiratory Distress Syndrome (hypoxemic respiratory failure not explained by cardiac disease + PaO/FiO ratio < 300 with a Positive End-Expiratory Pressure ≥ 5 cm HO + bilateral pulmonary infiltrates) Length of mechanical ventilation of at least 72 hours Informed consent (next of kin / legal guardian) Exclusion criteria: Pregnant or breast-feeding women. Terminal disease (advanced cancer; under palliative care; cardiovascular, respiratory, or renal disease with a life expectancy less ≤ 1 year). Therapeutic limitation (advance directives or do not resuscitate order) Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents, active cancer). Patients under chronic treatment with glucocorticoids for other diseases (≥ 8 mg prednisone, or equivalent) Participation in another randomized clinical trial. INTERVENTION AND COMPARATOR:Eligible patients will be randomized to receive standard ICU patient care (group 1) or standard ICU patient care plus high dose dexamethasone (group 2). Group 1: dexamethasone up to 6 mg/24 hours for up to 10 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. Group 2: dexamethasone 16 mg/24 hours for 5 days followed by dexamethasone 8 mg/24 hours for 5 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. MAIN OUTCOME:The main result is ventilator-free days at 28 days (Days without ventilator support in the first 28 days following randomization). Secondary outcomes are 28-days and 90-days mortality, frequency of nosocomial infections in the first 28 days after randomization, Sequential Organ Failure Assessment (SOFA) score variation and prone position in the first 10-days, viral shedding 28-days after randomization, and delirium and muscle weakness at ICU discharge. RANDOMISATION:Treatment will be assigned according to site stratified randomization by permuted random blocks sequence 1:1 generated with a table in R language concealed in a randomization tool in REDCap (Research Electronic Data CAPture) platform. BLINDING (MASKING):This is an open trial, so no masking of treatment assignment will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE):Assuming a 3 days difference in ventilator-free days between treatment groups, with a mean of 9 days, and a standard deviation of 9 days; the necessary sample size would be 284 subjects (142 per group), with a power of 80% and a two-tailed alpha error of 0.05. TRIAL STATUS:The protocol with code 1264, version 3.0 on date: May 13, 2020 is approved by the local Ethics Committee. The trial is in the recruitment phase. Recruitment began May 22, 2020 and is anticipated to be complete by the end of December 2021. TRIAL REGISTRATION:The trial was registered under the title "Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial" with ClinicalTrials number NCT04395105, https://clinicaltrials.gov/ct2/show/NCT04395105 , registered on 20 May 2020. 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. 10.1186/s13063-020-04646-y
    [Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome]. Pan C,Xie J F,Qiu H B,Yang Y Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS. 10.3760/cma.j.cn501120-20200407-00214
    Double-blind, randomized, controlled, trial to assess the efficacy of allogenic mesenchymal stromal cells in patients with acute respiratory distress syndrome due to COVID-19 (COVID-AT): A structured summary of a study protocol for a randomised controlled trial. Payares-Herrera Concepción,Martínez-Muñoz María E,Vallhonrat Inés Lipperheide,de Molina Rosa Malo,Torres Manuel Pérez,Trisan Andrea,de Diego Isabel Salcedo,Alonso Rosalía,Zafra Rocío,Donaire Trinidad,Sánchez Rocío,Rubio Juan José,Duarte Palomino Rafael F,Solá Cristina Avendaño Trials OBJECTIVES:1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN:A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS:The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 10 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES:Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION:The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING):To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE):A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS:Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION:EudraCT Number: 2020-002193-27 , registered on July 14, 2020. NCT number: NCT04615429 , registered on November 4, 2020. 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. 10.1186/s13063-020-04964-1
    A Community-transmitted Case of Severe Acute Respiratory Distress Syndrome (SARS) Due to SARS-CoV-2 in the United States. Sanville Bradley,Corbett Rebecca,Pidcock Wesley,Hardin Kaitlyn,Sebat Christian,Nguyen Minh-Vu,Thompson George R,Haczku Angela,Schivo Michael,Cohen Stuart Clinical infectious diseases : an official publication of the Infectious Diseases Society of America This is the first known community transmission case of the novel coronavirus disease (COVID-19) in the United States, with significant public health implications. Diagnosis of COVID-19 is currently confirmed with PCR based testing of appropriate respiratory samples. Given the absence of travel or known exposure history, this patient did not meet the criteria for testing according to CDC guidelines at the time of her presentation. Since this case, any patient with severe disease (eg, ARDS or pneumonia) requiring hospitalization without an explanatory diagnosis can be tested even if no clear source of exposure is identified. While influencing national health policies for revising screening criteria, this case also highlighted significant knowledge gaps in diagnosis and treatment and a desperate need for early, widespread, fast and cheap testing for COVID-19. 10.1093/cid/ciaa347
    A Case of Extracorporeal Membrane Oxygenation as a Salvage Therapy for COVID-19-Associated Severe Acute Respiratory Distress Syndrome: Mounting Evidence. Rajdev Kartikeya,Farr Lyndie A,Saeed Muhammad Ahsan,Hooten Rorak,Baus Joseph,Boer Brian Journal of investigative medicine high impact case reports Coronavirus disease 2019 (COVID-19) caused by a novel human coronavirus has led to a tsunami of viral illness across the globe, originating from Wuhan, China. Although the value and effectiveness of extracorporeal membrane oxygenation (ECMO) in severe respiratory illness from COVID-19 remains unclear at this time, there is emerging evidence suggesting that it could be utilized as an ultimate treatment in appropriately selected patients not responding to conventional care. We present a case of a 32-year-old COVID-19 positive male with a history of diabetes mellitus who was intubated for severe acute respiratory distress syndrome (ARDS). The patient's hypoxemia failed to improve despite positive pressure ventilation, prone positioning, and use of neuromuscular blockade for ventilator asynchrony. He was evaluated by a multidisciplinary team for considering ECMO for refractory ARDS. He was initiated on venovenous ECMO via dual-site cannulation performed at the bedside. Although his ECMO course was complicated by bleeding, he showed a remarkable improvement in his lung function. ECMO was successfully decannulated after 17 days of initiation. The patient was discharged home after 47 days of hospitalization without any supplemental oxygen and was able to undergo active physical rehabilitation. A multidisciplinary approach is imperative in the initiation and management of ECMO in COVID-19 patients with severe ARDS. While ECMO is labor-intensive, using it in the right phenotype and in specialized centers may lead to positive results. Patients who are young, with fewer comorbidities and single organ dysfunction portray a better prognosis for patients in which ECMO is utilized. 10.1177/2324709620957778
    The case for chronotherapy in Covid-19-induced acute respiratory distress syndrome. Tamimi Faleh,Abusamak Mohammad,Akkanti Bindu,Chen Zheng,Yoo Seung-Hee,Karmouty-Quintana Harry British journal of pharmacology Coronavirus disease 2019 (COVID-19), the disease resulting from infection by a novel coronavirus, SARS-Cov2, has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over four million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of acute respiratory distress syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS, and thus, chronotherapy may be used to effectively manage ARDS in COVID-19 patients. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc. 10.1111/bph.15140
    Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of SARS-CoV-2-Induced Acute Respiratory Distress Syndrome. Harrell Carl Randall,Jovicic Biljana Popovska,Djonov Valentin,Volarevic Vladislav Analytical cellular pathology (Amsterdam) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the development of a new coronavirus disease (COVID-19), is a highly transmittable virus which, in just ten months, infected more than 40 million people in 214 countries worldwide. After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS). Since there are no specific drugs or vaccines available to cure or prevent COVID-19 infection and COVID-19-related ARDS, a new therapeutic agent which will support oxygen supply and, at the same time, efficiently alleviate SARS-CoV-2-induced lung inflammation is urgently needed. Due to their potent immuno- and angiomodulatory characteristics, mesenchymal stem cells (MSCs) may increase oxygen supply in the lungs and may efficiently alleviate ongoing lung inflammation, including SARS-CoV-2-induced ARDS. In this review article, we described molecular mechanisms that are responsible for MSC-based modulation of immune cells which play a pathogenic role in the development of SARS-CoV-2-induced ARDS and we provided a brief outline of already conducted and ongoing clinical studies that increase our understanding about the therapeutic potential of MSCs and their secretome in the therapy of COVID-19-related ARDS. 10.1155/2020/1939768
    Management of Respiratory Distress Syndrome due to COVID-19 infection. Navas-Blanco Jose R,Dudaryk Roman BMC anesthesiology The management of Acute Respiratory Distress Syndrome (ARDS) secondary to the novel Coronavirus Disease 2019 (COVID-19) proves to be challenging and controversial. Multiple studies have suggested the likelihood of an atypical pathophysiology to explain the spectrum of pulmonary and systemic manifestations caused by the virus. The principal paradox of COVID-19 pneumonia is the presence of severe hypoxemia with preserved pulmonary mechanics. Data derived from the experience of multiple centers around the world have demonstrated that initial clinical efforts should be focused into avoid intubation and mechanical ventilation in hypoxemic COVID-19 patients. On the other hand, COVID-19 patients progressing or presenting into frank ARDS with typical decreased pulmonary compliance, represents another clinical enigma to many clinicians, since routine therapeutic interventions for ARDS are still a subject of debate. 10.1186/s12871-020-01095-7
    Novel risk scoring system for predicting acute respiratory distress syndrome among hospitalized patients with coronavirus disease 2019 in Wuhan, China. Liang Mengyuan,He Miao,Tang Jian,He Xinliang,Liu Zhijun,Feng Siwei,Chen Ping,Li Hui,Xue Yu'e,Bai Tao,Ma Yanling,Zhang Jianchu BMC infectious diseases BACKGROUND:The mortality rate from acute respiratory distress syndrome (ARDS) is high among hospitalized patients with coronavirus disease 2019 (COVID-19). Hence, risk evaluation tools are required to immediately identify high-risk patients upon admission for early intervention. METHODS:A cohort of 220 consecutive patients with COVID-19 were included in this study. To analyze the risk factors of ARDS, data obtained from approximately 70% of the participants were randomly selected and used as training dataset to establish a logistic regression model. Meanwhile, data obtained from the remaining 30% of the participants were used as test dataset to validate the effect of the model. RESULTS:Lactate dehydrogenase, blood urea nitrogen, D-dimer, procalcitonin, and ferritin levels were included in the risk score system and were assigned a score of 25, 15, 34, 20, and 24, respectively. The cutoff value for the total score was > 35, with a sensitivity of 100.00% and specificity of 81.20%. The area under the receiver operating characteristic curve and the Hosmer-Lemeshow test were 0.967 (95% confidence interval [CI]: 0.925-0.989) and 0.437(P Value = 0.437). The model had excellent discrimination and calibration during internal validation. CONCLUSIONS:The novel risk score may be a valuable risk evaluation tool for screening patients with COVID-19 who are at high risk of ARDS. 10.1186/s12879-020-05561-y
    Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial. Desilles J P,Gregoire C,Le Cossec C,Lambert J,Mophawe O,Losser M R,Lambiotte F,Le Tacon S,Cantier M,Engrand N,Trouiller P,Pottecher J Trials OBJECTIVES:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may trigger severe pneumonia in coronavirus disease of 2019 (COVID-19) patients through release of damage-associated molecular patterns (DAMPs) and recruitment of neutrophils in the lungs. Activated neutrophils induce inflammation and severe alveolar injury by releasing neutrophil extracellular traps (NETs). The backbones of many DAMPs and NETs are made of extracellular, cell-free DNA decorated with highly toxic compounds such as elastase, myeloperoxidase and citrullinated histones. Dornase alfa is a FDA-approved recombinant human DNAse 1 for the treatment of cystic fibrosis, which cleaves extracellular DNA and may break up cell-free DNA, loosening sticky mucus in the distal airways and reducing NETs-induced toxicity on alveolar pneumocytes. The COVIDornase trial intends to define the impact of aerosolized intra-tracheal dornase alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs. TRIAL DESIGN:COVIDornase is a prospective, randomized, controlled, 2-arm (1:1 ratio), multicentric, open-label clinical trial. PARTICIPANTS:The study will recruit mechanically ventilated patients hospitalized in the intensive care unit (ICU) in the recruiting centres (at the time of writing: The Rothschild foundation hospital in Paris, the Strasbourg university hospitals, and Metz-Thionville hospital) who have been diagnosed with COVID-19 and meet ARDS criteria. INCLUSION CRITERIA:- Adult patient (age ≥ 18 years old); - Hospitalized in ICU; - With severe COVID-19 pneumonia and ARDS according to Berlin criteria (PaO/FiO < 300 and PEEP > 5 cmHO); - Intubated for less than 8 days; - With an anticipated duration of mechanical ventilation > 48 hours; - Carrier of an arterial catheter; - For whom 4 PaO/FiO values over the preceding 24 hours are available; NON-INCLUSION CRITERIA: - Known hypersensitivity to dornase alfa or any of its excipients; - Pregnant or breastfeeding status; - Patient under legal protection. INTERVENTION AND COMPARATOR:Intervention 1, Study group Dornase alfa (Pulmozyme®, Roche, Switzerland) will be administered by aerosol, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer (Aerogen Solo®, Aerogen, Ireland). The remainder of the management will be performed in accordance with good clinical practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmHO, tracheal balloon pressure check every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30 cmHO), neuromuscular blockers if necessary, prone position if PaO/FiO < 150, early enteral nutrition, glycemic control and a sedation protocol based on the RASS score. Intervention 2, Comparator Patients will receive usual care in accordance with good practice (as detailed above), without aerosols. MAIN OUTCOMES:The primary outcome is the occurrence of at least one grade improvement between D (inclusion) and D in the ARDS scale severity (Berlin criteria). For instance from "severe" to "moderate" or from "moderate" to "mild". RANDOMISATION:All consecutive patients meeting the inclusion criteria will be randomised 1:1 using an eCRF-based, computer-generated randomisation table, either to the dornase alfa arm or to the control arm. An interim analysis will be performed after inclusion of 20 patients. Inclusions may be stopped at the interim analysis per data safety and monitoring board (DSMB) advice, if statistical analyses conclude on the futility or efficacy of the intervention or by other DSMB decision. BLINDING (MASKING):The participants and caregivers will not be blinded to study group assignment. Those assessing the outcomes will be blinded to study group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE):Fifty patients will be randomized to each group, 100 patients in total. TRIAL STATUS:Protocol version number 2, April 29, 2020. Recruitment is ongoing. The trial started recruitment on the 21 April 2020. We estimate recruitment will finish August 21 2020. TRIAL REGISTRATION:The trial was registered in ClinicalTrials.gov on 21 April 2020, updated on 8 May 2020. Trial registration number is NCT04355364. 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. 10.1186/s13063-020-04488-8
    Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Hasan Syed Shahzad,Capstick Toby,Ahmed Raees,Kow Chia Siang,Mazhar Faizan,Merchant Hamid A,Zaidi Syed Tabish Razi Expert review of respiratory medicine OBJECTIVES:The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019). We systematically reviewed mortality in COVID-19 patients with ARDS and the potential role of systemic corticosteroids in COVID-19 patients. METHODS:Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle-Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS. RESULTS:The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23-56%). The pooled mortality estimate for China was 69% (95% CI: 67-72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58-86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2-29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%). CONCLUSIONS:The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients. 10.1080/17476348.2020.1804365
    Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets. Karmouty-Quintana Harry,Thandavarayan Rajarajan A,Keller Steven P,Sahay Sandeep,Pandit Lavannya M,Akkanti Bindu International journal of molecular sciences The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested. 10.3390/ijms21218081
    Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. Quesada-Gomez Jose Manuel,Entrenas-Castillo Marta,Bouillon Roger The Journal of steroid biochemistry and molecular biology Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months. 10.1016/j.jsbmb.2020.105719
    2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation. Albarello Fabrizio,Pianura Elisa,Di Stefano Federica,Cristofaro Massimo,Petrone Ada,Marchioni Luisa,Palazzolo Claudia,Schininà Vincenzo,Nicastri Emanuele,Petrosillo Nicola,Campioni Paolo,Eskild Petersen,Zumla Alimuddin,Ippolito Giuseppe, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases INTRODUCTION:Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. OBJECTIVE:We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). RESULTS:Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. CONCLUSIONS:Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment. 10.1016/j.ijid.2020.02.043
    Severe Acute Respiratory Distress Syndrome Secondary to Coronavirus 2 (SARS-CoV-2). Maveddat Ashley,Mallah Haneen,Rao Sanjana,Ali Kiran,Sherali Samir,Nugent Kenneth The international journal of occupational and environmental medicine The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has created a worldwide pandemic. Many patients with this infection have an asymptomatic or mild illness, but a small percentage of patients require hospitalization and intensive care. Patients with respiratory tract involvement have a spectrum of presentations that range from scattered ground-glass infiltrates to diffuse infiltrates with consolidation. Patients with the latter radiographic presentation have severe hypoxemia and usually require mechanical ventilation. In addition, some patients develop multiorgan failure, deep venous thrombi with pulmonary emboli, and cytokine storm syndrome. The respiratory management of these patients should focus on using low tidal volume ventilation with low intrathoracic pressures. Some patients have significant recruitable lung and may benefit from higher positive end-expiratory pressure (PEEP) levels and/or prone positioning. There is no well-established anti-viral treatment for this infection; the United States Food and Drug Administration (FDA) has provided emergency use authorization for convalescent plasma and remdesivir for the treatment of patients with COVID-19. In addition, randomized trials have demonstrated that dexamethasone improves outcomes in patients on mechanical ventilators or on oxygen. There are ongoing trials of other drugs which have the potential to moderate the acute inflammatory state seen in some of these patients. These patients often need prolonged high-level intensive care. Hospitals are confronted with significant challenges in patient management, supply management, health care worker safety, and health care worker burnout. 10.34172/ijoem.2020.2202
    Severe acute respiratory distress syndrome in coronavirus disease 2019-infected pregnancy: obstetric and intensive care considerations. Schnettler William T,Al Ahwel Yousef,Suhag Anju American journal of obstetrics & gynecology MFM Since the emergence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2) in Wuhan, China, at the end of December 2019, coronavirus disease 2019 has been associated with severe morbidity and mortality and has left world governments, healthcare systems, and providers caring for vulnerable populations, such as pregnant women, wrestling with the optimal management strategy. Unique physiologic and ethical considerations negate a one-size-fits-all approach when caring for critically ill pregnant women with coronavirus disease 2019, and few resources exist to guide the multidisciplinary team through decisions regarding optimal maternal-fetal surveillance, intensive care procedures, and delivery timing. We present a case of rapid clinical decompensation and development of severe acute respiratory distress syndrome in a woman at 31 weeks' gestation to highlight these unique considerations and present an algorithmic approach to the diagnosis and management of the disease. 10.1016/j.ajogmf.2020.100120
    The novel coronavirus disease (COVID-19) complicated by pulmonary embolism and acute respiratory distress syndrome. Li Ting,Cheng Guang-Shing,Pipavath Sudhakar N J,Kicska Gregory A,Liu Liangjin,Kinahan Paul E,Wu Wei Journal of medical virology Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID-19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID-19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID-19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID-19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID-19 may be related to PE and not necessarily always due to the parenchymal disease. 10.1002/jmv.26068
    Acute respiratory distress syndrome (ARDS) caused by the novel coronavirus disease (COVID-19): a practical comprehensive literature review. Montenegro Francisco,Unigarro Luis,Paredes Gustavo,Moya Tatiana,Romero Ana,Torres Liliana,López Juan Carlos,González Fernando Esteban Jara,Del Pozo Gustavo,López-Cortés Andrés,Diaz Ana M,Vasconez Eduardo,Cevallos-Robalino Doménica,Lister Alex,Ortiz-Prado Esteban Expert review of respiratory medicine INTRODUCTION:The exponential growth of SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on most health systems around the world. The complications derived from the novel coronavirus disease (COVID-19) vary due to comorbidities, sex and age, with more than 50% of the patients requiring some level of intensive care developing acute respiratory distress syndrome (ARDS). The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological, and radiological presentation as well as the current treatment strategies. AREAS COVERED:Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The new treatment strategies are updated, and the analysis of the physiopathology is included in this review. EXPERT OPINION:ARDS is one of the most frequent complications in patients with COVID-19. Information regarding the etiology and physiopathology are still unfolding and for the prevention and amelioration, good clinical management, adequate ventilatory support and the use of systemic corticoids seem to be the most efficient way to reduce mortality and to reduce hospital lengths. 10.1080/17476348.2020.1820329
    A Perspective on Erythropoietin as a Potential Adjuvant Therapy for Acute Lung Injury/Acute Respiratory Distress Syndrome in Patients with COVID-19. Sahebnasagh Adeleh,Mojtahedzadeh Mojataba,Najmeddin Farhad,Najafi Atabak,Safdari Mohammadreza,Rezai Ghaleno Hassan,Habtemariam Solomon,Berindan-Neagoe Ioana,Nabavi Seyed Mohammad Archives of medical research The novel coronavirus 2019-nCoV (SARS-CoV-2) infection that emerged in China in December 2019 has rapidly spread to become a global pandemic. This article summarizes the potential benefits of erythropoietin (EPO) in alleviating SARS-CoV-2 pathogenesis which is now called COVID-19. As with other coronavirus infection, the lethality of COVID-19 is associated with respiratory dysfunction due to overexpression of proinflammatory cytokines induced by the host immune responses. The resulting cytokine storm leads to the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Erythropoietin, well known for its role in the regulation of erythropoiesis, may have protective effects against ALI/ARDS induced by viral and other pathogens. EPO exerts antiapoptotic and cytoprotective properties under various pathological conditions. With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways. Thus, it may be considered as a safe drug candidate for COVID-19 patients if given at the early stage of the disease. The potential effects of erythropoietin on different aspects of ALI/ARDS associated with SARS-CoV-2 infection are reviewed. 10.1016/j.arcmed.2020.08.002