Invasive pulmonary aspergillosis complicating COVID-19 in the ICU - A case report.

It is not yet known, if critically ill COVID-19 patients are prone to fungal infections. We report a 69-year-old patient without typical risk factors for invasive pulmonary aspergillosis (IPA), who developed IPA two weeks after onset of symptoms. Our report shows that IPA may occur in critically ill COVID-19 patients

Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?

Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly

The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future.

The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues

Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19.

ObjectivesTo describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19.DesignRetrospective, observational study.SettingThe Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY.PatientsAdult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021.InterventionsHospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100.Measurements and main resultsAmong 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49).ConclusionsDuring the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed

Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases

Purpose: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. Methods: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. Conclusion: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia

The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi-organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10-15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose-binding lectin). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high-affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low-moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID-19 facilitates re-inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto-inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time-/sequence-dependent" model has several implications for prevention, diagnosis, and therapy of COVID-19 at all ages

Immunohistochemical findings in the lungs of COVID-19 subjects: Evidence of surfactant dysregulation

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARSCoV-2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration. PATIENTS AND METHODS: We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARSCoV-2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B). RESULTS: In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces. CONCLUSIONS: Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant

ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients’ representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research

COVID‐19: The Uninvited Guest in the Intensive Care Unit — Implications for Pharmacotherapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155543/1/phar2394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155543/2/phar2394_am.pd

Coronavirus (COVID-19) Fulminant Myopericarditis and Acute Respiratory Distress Syndrome (ARDS) in a Middle-Aged Male Patient

Myopericarditis remains a prominent infectious inflammatory disorder throughout a patient\u27s lifetime. Moreover, viral pathogens have been proven to be the leading contributors to myopericarditis in the pediatric and adult populations. Despite the current comprehensive knowledge of myocardial injury in viral and post-viral myopericarditis, the cellular and molecular mechanisms of SARS-CoV-2-induced myopericarditis are poorly understood. This report presents a case of coronavirus (COVID-19) fulminant myopericarditis and acute respiratory distress syndrome (ARDS) in a middle-aged male patient: a 51-year-old man with a history of hypertension who arrived to the emergency department with a dry cough, fatigue, dyspnea, and a fever. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay confirmed a diagnosis of COVID-19 infection, resulting in the patient\u27s admission to the airborne isolation unit for clinical observation. When his condition began to deteriorate, the patient was transferred to the cardiac care unit after electrocardiography detected cardiac injury, demonstrating diffuse ST-segment elevation. Laboratory evaluations revealed elevated troponin T and BNP, with an echocardiogram indicating global left ventricular hypokinesia and a reduced ejection fraction. The patient was treated with hydroxychloroquine, azithromycin, dobutamine, remdesivir, and ventilatory support. This specific case highlights the severity and complications that may arise as a direct result of COVID-19 infection