• Acute respiratory distress syndrome (ARDS) as an adverse event following immunization: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

      Serazin, Nathan A; Edem, Bassey; Williams, Sarah R; Ortiz, Justin R; Kawade, Anand; Das, Manoj Kumar; Šubelj, Maja; Edwards, Kathryn M; Parida, Shreemanta K; Wartel, T Anh; et al. (Elsevier Ltd., 2021-01-28)
      This is a Brighton Collaboration Case Definition of the term “Acute Respiratory Distress Syndrome – ARDS” to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated in this final manuscript. © 2021 The Authors
    • Functional pathophysiology of SARS-CoV-2-induced acute lung injury and clinical implications

      Habashi, N.M.; Camporota, L.; Gatto, L.A.; Nieman, G. (American Physiological Society, 2021-01-14)
      The worldwide pandemic caused by the SARS-CoV-2 virus has resulted in over 84,407,000 cases, with over 1,800,000 deaths when this paper was submitted, with comorbidities such as gender, race, age, body mass, diabetes, and hypertension greatly exacerbating mortality. This review will analyze the rapidly increasing knowledge of COVID-19-induced lung pathophysiology. Although controversial, the acute respiratory distress syndrome (ARDS) associated with COVID-19 (CARDS) seems to present as two distinct phenotypes: type L and type H. The “L” refers to low elastance, ventilation/perfusion ratio, lung weight, and recruitability, and the “H” refers to high pulmonary elastance, shunt, edema, and recruitability. However, the LUNG-SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) and ESICM (European Society of Intensive Care Medicine) Trials Groups have shown that 13% of the mechanically ventilated non-COVID-19 ARDS patients have the type-L phenotype. Other studies have shown that CARDS and ARDS respiratory mechanics overlap and that standard ventilation strategies apply to these patients. The mechanisms causing alterations in pulmonary perfusion could be caused by some combination of 1) renin-angiotensin system dysregulation, 2) thrombosis caused by loss of endothelial barrier, 3) endothelial dysfunction causing loss of hypoxic pulmonary vasoconstriction perfusion control, and 4) hyperperfusion of collapsed lung tissue that has been directly measured and supported by a computational model. A flowchart has been constructed highlighting the need for personalized and adaptive ventilation strategies, such as the time-controlled adaptive ventilation method, to set and adjust the airway pressure release ventilation mode, which recently was shown to be effective at improving oxygenation and reducing inspiratory fraction of oxygen, vasopressors, and sedation in patients with COVID-19.
    • Ramatroban for chemoprophylaxis and treatment of COVID-19: David takes on Goliath.

      Chiang, Kate C; Rizk, John G; Nelson, Deanna J; Krishnamurti, Lakshmanan; Subbian, Selvakumar; Imig, John D; Khan, Imran; Reddy, Srinivasa T; Gupta, Ajay (Taylor and Francis Inc., 2022-02-22)
      In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB2 ≫ PGE2 > PGD2 in the lungs, and 11-dehydro-TxB2, a TxA2 metabolite, in the systemic circulation. While TxA2 stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB2 is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD2. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA2/TP and PGD2/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.
    • Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients

      Tabibi, Seena; Tabibi, Tara; Conic, Rosalynn R. Z.; Banisaeed, Nassim; Streiff, Michael B. (SAGE Publications, 2020-07-15)
      In the 5 months since initial reports of COVID-19 came to light, the death toll due to SARS-CoV-2 has rapidly increased. The morbidity and mortality of the infection varies based upon patient age, comorbid conditions, viral load, and the availability of effective treatments. Findings from limited autopsies, clinical observations, and laboratory data suggest that high cytokine levels and a procoagulant state can precipitate acute respiratory distress syndrome and multi-organ dysfunction syndrome in critically ill patients. To complicate matters, comorbidities may affect the response to medical treatments currently in use, all of which are still in trial phase. Therapeutic plasma exchange (TPE) merits consideration in the treatment of critically ill COVID-19 patients and is an avenue for clinical trials to pursue. If efficacious, faster recovery of patients may lead to shorter intensive care unit stays and less time on mechanical ventilation. Herein, we briefly discuss some of the various approaches currently being investigated for the treatment of SARS-CoV-2 with a focus on potential benefits of TPE for selected critically ill patients. © The Author(s) 2020.
    • The US Strategic National Stockpile Ventilators in Coronavirus Disease 2019: A Comparison of Functionality and Analysis Regarding the Emergency Purchase of 200,000 Devices

      Branson, Rich; Dichter, Jeffrey R; Feldman, Henry; Devereaux, Asha; Dries, David; Benditt, Joshua; Hossain, Tanzib; Ghazipura, Marya; King, Mary; Baldisseri, Marie; et al. (Elsevier Inc., 2020-09-21)
      Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was serious concern that the United States would encounter a shortfall of mechanical ventilators. In response, the US government, using the Defense Production Act, ordered the development of 200,000 ventilators from 11 different manufacturers. These ventilators have different capabilities, and whether all are able to support COVID-19 patients is not evident. Research Question: Evaluate ventilator requirements for affected COVID-19 patients, assess the clinical performance of current US Strategic National Stockpile (SNS) ventilators employed during the pandemic, and finally, compare ordered ventilators’ functionality based on COVID-19 patient needs. Study Design and Methods: Current published literature, publicly available documents, and lay press articles were reviewed by a diverse team of disaster experts. Data were assembled into tabular format, which formed the basis for analysis and future recommendations. Results: COVID-19 patients often develop severe hypoxemic acute respiratory failure and adult respiratory defense syndrome (ARDS), requiring high levels of ventilator support. Current SNS ventilators were unable to fully support all COVID-19 patients, and only approximately half of newly ordered ventilators have the capacity to support the most severely affected patients; ventilators with less capacity for providing high-level support are still of significant value in caring for many patients. Interpretation: Current SNS ventilators and those on order are capable of supporting most but not all COVID-19 patients. Technologic, logistic, and educational challenges encountered from current SNS ventilators are summarized, with potential next-generation SNS ventilator updates offered. © 2020 American College of Chest Physicians